{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:17:17Z","timestamp":1793344637459,"version":"4.5.0"},"reference-count":165,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurocrit Care"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Within 2\u00a0min of severe ischemia, spreading depolarization (SD) propagates like a wave through compromised gray matter of the higher brain. More SDs arise over hours in adjacent tissue, expanding the neuronal damage. This period represents a therapeutic window to inhibit SD and so reduce impending tissue injury. Yet most neuroscientists assume that the course of early brain injury can be explained by glutamate excitotoxicity, the concept that immediate glutamate release promotes early and downstream brain injury. There are many problems with glutamate release being the unseen culprit, the most practical being that the concept has yielded zero therapeutics over the past 30\u00a0years. But the basic science is also flawed, arising from dubious foundational observations beginning in the 1950s<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Literature pertaining to excitotoxicity and to SD over the past 60 years is critiqued.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Excitotoxicity theory centers on the immediate and excessive release of glutamate with resulting neuronal hyperexcitation. This instigates poststroke cascades with subsequent secondary neuronal injury. By contrast,  SD theory argues that although SD evokes some brief glutamate release, acute neuronal damage and the subsequent cascade of injury to neurons are elicited by the metabolic stress of SD, not by excessive glutamate release. The challenge we present here is to find new clinical targets based on more informed basic science. This is motivated by the continuing failure by neuroscientists and by industry to develop drugs that can reduce brain injury following ischemic stroke, traumatic brain injury, or sudden cardiac arrest. One important step is to recognize that SD plays a central role in promoting early neuronal damage. We argue that uncovering the molecular biology of SD initiation and propagation is essential because ischemic neurons are usually not acutely injured unless SD propagates through them. The role of  glutamate excitotoxicity theory and how it has shaped SD research is then addressed, followed by a critique of its fading relevance to the study of brain injury.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Spreading depolarizations better account for\u00a0the acute neuronal injury arising from brain\u00a0ischemia than does the\u00a0early and excessive release of glutamate.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12028-021-01429-4","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T18:03:01Z","timestamp":1645552981000},"page":"11-30","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Questioning Glutamate Excitotoxicity in Acute Brain Damage: The Importance of Spreading Depolarization"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-7314","authenticated-orcid":false,"given":"R. David","family":"Andrew","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Farkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jed A.","family":"Hartings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. C.","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Herreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei. A.","family":"Kirov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cenk","family":"Ayata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Ollen-Bittle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Reiffurth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Revah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Meldrum","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken D.","family":"Dawson-Scully","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghanim","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens P.","family":"Dreier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"1429_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-021-01431-w","author":"RD Andrew","year":"2021","unstructured":"Andrew RD, Hartings JA, Ayata C, Brennan KC, Dawson-Scully KD, Farkas E, et al. The critical role of spreading depolarizations in early brain injury: consensus and contention. Neurocrit Care. 2021. https:\/\/doi.org\/10.1007\/s12028-021-01431-w.","journal-title":"Neurocrit Care"},{"key":"1429_CR2","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/cercor\/bhk032","volume":"17","author":"RD Andrew","year":"2007","unstructured":"Andrew RD, Labron MW, Boehnke SE, Carnduff L, Kirov SA. Physiological evidence that pyramidal neurons lack functional water channels. Cereb Cortex. 2007;17:787\u2013802.","journal-title":"Cereb Cortex"},{"key":"1429_CR3","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1073\/pnas.1700760114","volume":"114","author":"JP Dreier","year":"2017","unstructured":"Dreier JP, Reiffurth C. Exploitation of the spreading depolarization-induced cytotoxic edema for high-resolution, 3D mapping of its heterogeneous propagation paths. Proc Natl Acad Sci U S A. 2017;114:2112\u20134.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1429_CR4","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-021-01326-w","author":"JA Hellas","year":"2017","unstructured":"Hellas JA, Andrew RD. Neuronal swelling: a non-osmotic consequence of spreading depolarization. Neurocrit Care. 2021. https:\/\/doi.org\/10.1007\/s12028-021-01326-w.","journal-title":"Neurocrit Care"},{"key":"1429_CR5","doi-asserted-by":"crossref","first-page":"eaax7171","DOI":"10.1126\/science.aax7171","volume":"367","author":"H Mestre","year":"2020","unstructured":"Mestre H, Du T, Sweeney AM, Liu G, Samson AJ, Peng W, et al. Cerebrospinal fluid influx drives acute ischemic tissue swelling. Science (New York, NY). 2020;367:eaax7171.","journal-title":"Science (New York, NY)"},{"key":"1429_CR6","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.neuron.2015.04.004","volume":"86","author":"JP Dreier","year":"2015","unstructured":"Dreier JP, Reiffurth C. The Stroke\u2013Migraine depolarization continuum. Neuron. 2015;86:902\u201322.","journal-title":"Neuron"},{"key":"1429_CR7","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1093\/brain\/awl392","volume":"130","author":"AJ Strong","year":"2007","unstructured":"Strong AJ, Anderson PJ, Watts HR, Virley DJ, Lloyd A, Irving EA, et al. Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex. Brain J Neurol. 2007;130:995\u20131008.","journal-title":"Brain J Neurol"},{"key":"1429_CR8","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1212\/WNL.0b013e3182886932","volume":"80","author":"J Woitzik","year":"2013","unstructured":"Woitzik J, Hecht N, Pinczolits A, Sandow N, Major S, Winkler MKL, et al. Propagation of cortical spreading depolarization in the human cortex after malignant stroke. Neurology. 2013;80:1095\u2013102.","journal-title":"Neurology"},{"key":"1429_CR9","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nm.2333","volume":"17","author":"JP Dreier","year":"2011","unstructured":"Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med. 2011;17:439\u201347.","journal-title":"Nat Med"},{"key":"1429_CR10","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/ana.25147","volume":"83","author":"JP Dreier","year":"2018","unstructured":"Dreier JP, Major S, Foreman B, Winkler MKL, Kang EJ, Milakara D, et al. Terminal spreading depolarization and electrical silence in death of human cerebral cortex. Ann Neurol. 2018;83:295\u2013310.","journal-title":"Ann Neurol"},{"key":"1429_CR11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3389\/fnins.2019.00373","volume":"13","author":"JP Dreier","year":"2019","unstructured":"Dreier JP, Major S, Lemale CL, Kola V, Reiffurth C, Schoknecht K, et al. Correlates of spreading depolarization, spreading depression, and negative ultraslow potential in epidural versus subdural electrocorticography. Front Neurosci. 2019;13:373.","journal-title":"Front Neurosci"},{"key":"1429_CR12","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/brain\/awy325","volume":"142","author":"ICM Loonen","year":"2019","unstructured":"Loonen ICM, Jansen NA, Cain SM, Schenke M, Voskuyl RA, Yung AC, et al. Brainstem spreading depolarization and cortical dynamics during fatal seizures in Cacna1a S218L mice. Brain. 2019;142:412\u201325.","journal-title":"Brain"},{"key":"1429_CR13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/jcbfm.2010.191","volume":"31","author":"M Lauritzen","year":"2011","unstructured":"Lauritzen M, Dreier JP, Fabricius M, Hartings JA, Graf R, Strong AJ. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab. 2011;31:17\u201335.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR14","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.wneu.2019.10.048","volume":"134","author":"S Soldozy","year":"2020","unstructured":"Soldozy S, Sharifi KA, Desai B, Giraldo D, Yeghyayan M, Liu L, et al. Cortical spreading depression in the setting of traumatic brain injury. World Neurosurg. 2020;134:50\u20137.","journal-title":"World Neurosurg"},{"key":"1429_CR15","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1152\/jn.1944.7.6.359","volume":"7","author":"AAP Leao","year":"1944","unstructured":"Leao AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol. 1944;7:359\u201390.","journal-title":"J Neurophysiol"},{"key":"1429_CR16","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1177\/0271678X16654496","volume":"37","author":"JP Dreier","year":"2017","unstructured":"Dreier JP, Fabricius M, Ayata C, Sakowitz OW, William Shuttleworth C, Dohmen C, et al. Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: review and recommendations of the COSBID research group. J Cereb Blood Flow Metab. 2017;37:1595\u2013625.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/01616412.1998.11740529","volume":"20","author":"M Kaminogo","year":"1998","unstructured":"Kaminogo M, Suyama K, Ichikura A, Onizuka M, Shibata S. Anoxic depolarization determines ischemic brain injury. Neurol Res. 1998;20:343\u20138.","journal-title":"Neurol Res"},{"key":"1429_CR18","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/brain\/awy102","volume":"141","author":"J L\u00fcckl","year":"2018","unstructured":"L\u00fcckl J, Lemale CL, Kola V, Horst V, Khojasteh U, Oliveira-Ferreira AI, et al. The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex. Brain. 2018;141:1734\u201352.","journal-title":"Brain"},{"key":"1429_CR19","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1161\/01.STR.23.4.552","volume":"23","author":"H Memezawa","year":"1992","unstructured":"Memezawa H, Smith ML, Siesjo BK. Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats. Stroke J Cereb Circ. 1992;23:552\u20139.","journal-title":"Stroke J Cereb Circ"},{"key":"1429_CR20","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/ana.21871","volume":"67","author":"A Nozari","year":"2010","unstructured":"Nozari A, Dilekoz E, Sukhotinsky I, Stein T, Eikermann-Haerter K, Liu C, et al. Microemboli may link spreading depression, migraine aura, and patent foramen ovale. Ann Neurol. 2010;67:221\u20139.","journal-title":"Ann Neurol"},{"key":"1429_CR21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/00008506-199404000-00005","volume":"6","author":"M Ayad","year":"1994","unstructured":"Ayad M, Verity MA, Rubinstein EH. Lidocaine delays cortical ischemic depolarization: relationship to electrophysiologic recovery and neuropathology. J Neurosurg Anesthesiol. 1994;6:98\u2013110.","journal-title":"J Neurosurg Anesthesiol"},{"key":"1429_CR22","doi-asserted-by":"crossref","first-page":"11602","DOI":"10.1523\/JNEUROSCI.23-37-11602.2003","volume":"23","author":"JA Hartings","year":"2003","unstructured":"Hartings JA, Rolli ML, Lu X-CM, Tortella FC. Delayed secondary phase of peri-infarct depolarizations after focal cerebral ischemia: relation to infarct growth and neuroprotection. J Neurosci Off J Soc Neurosci. 2003;23:11602\u201310.","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"1429_CR23","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1523\/JNEUROSCI.16-03-01219.1996","volume":"16","author":"C Largo","year":"1996","unstructured":"Largo C, Cuevas P, Somjen GG, Mart\u00edn Del R\u00edo R, Herreras O. The effect of depressing glial function in rat brain in situ on ion homeostasis, synaptic transmission, and neuron survival. J Neurosci. 1996;16:1219\u201329.","journal-title":"J Neurosci"},{"key":"1429_CR24","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.neuron.2015.02.007","volume":"85","author":"D von Bornst\u00e4dt","year":"2015","unstructured":"von Bornst\u00e4dt D, Houben T, Seidel JL, Zheng Y, Dilekoz E, Qin T, et al. Supply-demand mismatch transients in susceptible peri-infarct hot zones explain the origins of spreading injury depolarizations. Neuron. 2015;85:1117\u201331.","journal-title":"Neuron"},{"key":"1429_CR25","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1097\/00004647-199809000-00007","volume":"18","author":"JP Dreier","year":"1998","unstructured":"Dreier JP, K\u00f6rner K, Ebert N, G\u00f6rner A, Rubin I, Back T, et al. Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-l-arginine induces cortical spreading ischemia when K+ is increased in the subarachnoid space. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 1998;18:978\u201390.","journal-title":"J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"key":"1429_CR26","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.neuroscience.2013.12.032","volume":"260","author":"Z Bere","year":"2014","unstructured":"Bere Z, Obrenovitch TP, Bari F, Farkas E. Ischemia-induced depolarizations and associated hemodynamic responses in incomplete global forebrain ischemia in rats. Neuroscience. 2014;260:217\u201326.","journal-title":"Neuroscience"},{"key":"1429_CR27","doi-asserted-by":"crossref","first-page":"658","DOI":"10.3171\/jns.2000.93.4.0658","volume":"93","author":"JP Dreier","year":"2000","unstructured":"Dreier JP, Ebert N, Priller J, Megow D, Lindauer U, Klee R, et al. Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage? J Neurosurg. 2000;93:658\u201366.","journal-title":"J Neurosurg"},{"key":"1429_CR28","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/sj.jcbfm.9600252","volume":"26","author":"HK Shin","year":"2006","unstructured":"Shin HK, Dunn AK, Jones PB, Boas DA, Moskowitz MA, Ayata C. Vasoconstrictive neurovascular coupling during focal ischemic depolarizations. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2006;26:1018\u201330.","journal-title":"J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"key":"1429_CR29","first-page":"1","volume":"64","author":"AP Carlson","year":"2018","unstructured":"Carlson AP, Abbas M, Alunday RL, Qeadan F, Shuttleworth CW. Spreading depolarization in acute brain injury inhibited by ketamine: a prospective, randomized, multiple crossover trial. J Neurosurg. 2018;64:1\u20137.","journal-title":"J Neurosurg"},{"key":"1429_CR30","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/ana.21943","volume":"67","author":"B Bosche","year":"2010","unstructured":"Bosche B, Graf R, Ernestus RI, Dohmen C, Reithmeier T, Brinker G, et al. Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex. Ann Neurol. 2010;67:607\u201317.","journal-title":"Ann Neurol"},{"key":"1429_CR31","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1093\/brain\/awp102","volume":"132","author":"JP Dreier","year":"2009","unstructured":"Dreier JP, Major S, Manning A, Woitzik J, Drenckhahn C, Steinbrink J, et al. Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage. Brain. 2009;132:1866\u201381.","journal-title":"Brain"},{"key":"1429_CR32","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1093\/brain\/awu241","volume":"137","author":"JM Hinzman","year":"2014","unstructured":"Hinzman JM, Andaluz N, Shutter LA, Okonkwo DO, Pahl C, Strong AJ, et al. Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma. Brain J Neurol. 2014;137:2960\u201372.","journal-title":"Brain J Neurol"},{"key":"1429_CR33","first-page":"13","volume-title":"New strategies in stroke intervention","author":"MA Gottron","year":"2009","unstructured":"Gottron MA, Lo DC. The Na+\/K+-ATPase as a drug target for ischemic stroke. In: Annunziato L, editor. New strategies in stroke intervention. Totowa: Humana Press; 2009. p. 13\u201326."},{"key":"1429_CR34","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.2741\/1704","volume":"10","author":"M Dobretsov","year":"2005","unstructured":"Dobretsov M, Stimers JR. Neuronal function and alpha3 isoform of the Na\/K-ATPase. Front Biosci. 2005;10:2373\u201396.","journal-title":"Front Biosci"},{"key":"1429_CR35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0006-8993(93)91154-K","volume":"632","author":"G Czeh","year":"1993","unstructured":"Czeh G, Aitken PG, Somjen GG. Membrane currents in CA1 pyramidal cells during spreading depression (SD) and SD-like hypoxic depolarization. Brain Res. 1993;632:195\u2013208.","journal-title":"Brain Res"},{"key":"1429_CR36","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/00001756-199202000-00019","volume":"3","author":"G Cz\u00e9h","year":"1992","unstructured":"Cz\u00e9h G, Aitken PG, Somjen GG. Whole-cell membrane current and membrane resistance during hypoxic spreading depression. NeuroReport. 1992;3:197\u2013200.","journal-title":"NeuroReport"},{"key":"1429_CR37","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1152\/jn.00654.2004","volume":"93","author":"TR Anderson","year":"2005","unstructured":"Anderson TR, Jarvis CR, Biedermann AJ, Molnar C, Andrew RD. Blocking the anoxic depolarization protects without functional compromise following simulated stroke in cortical brain slices. J Neurophysiol. 2005;93:963\u201379.","journal-title":"J Neurophysiol"},{"key":"1429_CR38","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1152\/jn.2001.85.1.414","volume":"85","author":"I Joshi","year":"2001","unstructured":"Joshi I, Andrew RD. Imaging anoxic depolarization during ischemia-like conditions in the mouse hemi-brain slice. J Neurophysiol. 2001;85:414\u201324.","journal-title":"J Neurophysiol"},{"key":"1429_CR39","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1152\/jn.1997.78.2.891","volume":"78","author":"E Tanaka","year":"1997","unstructured":"Tanaka E, Yamamoto S, Kudo Y, Mihara S, Higashi H. Mechanisms underlying the rapid depolarization produced by deprivation of oxygen and glucose in rat hippocampal CA1 neurons in vitro. J Neurophysiol. 1997;78:891\u2013902.","journal-title":"J Neurophysiol"},{"key":"1429_CR40","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1523\/JNEUROSCI.5128-07.2008","volume":"28","author":"TH Murphy","year":"2008","unstructured":"Murphy TH, Li P, Betts K, Liu R. Two-photon imaging of stroke onset in vivo reveals that NMDA-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines. J Neurosci. 2008;28:1756\u201372.","journal-title":"J Neurosci"},{"key":"1429_CR41","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1161\/01.STR.0000166023.51307.e0","volume":"36","author":"GC Petzold","year":"2005","unstructured":"Petzold GC, Windm\u00fcller O, Haack S, Major S, Buchheim K, Megow D, et al. Increased extracellular K+ concentration reduces the efficacy of N-methyl-d-aspartate receptor antagonists to block spreading depression-like depolarizations and spreading ischemia. Stroke. 2005;36:1270\u20137.","journal-title":"Stroke"},{"key":"1429_CR42","doi-asserted-by":"crossref","first-page":"9859","DOI":"10.1523\/JNEUROSCI.1917-10.2010","volume":"30","author":"WC Risher","year":"2010","unstructured":"Risher WC, Ard D, Yuan J, Kirov SA. Recurrent spontaneous spreading depolarizations facilitate acute dendritic injury in the ischemic penumbra. J Neurosci. 2010;30:9859\u201368.","journal-title":"J Neurosci"},{"key":"1429_CR43","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1001\/archopht.1957.00940010205006","volume":"85","author":"DR Lucas","year":"1957","unstructured":"Lucas DR, Newhouse JP. The toxic effect of sodium l-glutamate on the inner layers of the retina. AMA Arch Ophthalmol. 1957;85:193\u2013201.","journal-title":"AMA Arch Ophthalmol"},{"key":"1429_CR44","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1126\/science.164.3880.719","volume":"164","author":"JW Olney","year":"1969","unstructured":"Olney JW. Brain lesions, obesity, and other disturbances in mice. Science. 1969;164:719\u201321.","journal-title":"Science"},{"key":"1429_CR45","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0006-8993(93)91644-8","volume":"612","author":"M Fabricius","year":"1993","unstructured":"Fabricius M, Jensen LHLM. Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex. Brain Res. 1993;612:61\u20139.","journal-title":"Brain Res"},{"key":"1429_CR46","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0165-0270(94)00202-R","volume":"59","author":"CP Taylor","year":"1995","unstructured":"Taylor CP, Burke SP, Weber ML. Hippocampal slices: glutamate overflow and cellular damage from ischemia are reduced by sodium-channel blockade. J Neurosci Methods. 1995;59:121\u20138.","journal-title":"J Neurosci Methods"},{"key":"1429_CR47","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S0306-4522(97)00259-5","volume":"81","author":"CC Toner","year":"1997","unstructured":"Toner CC, Stamford JA. Sodium channel blockade unmasks two temporally distinct mechanisms of striatal dopamine release during hypoxia\/hypoglycaemia in vitro. Neuroscience. 1997;81:999\u20131007.","journal-title":"Neuroscience"},{"key":"1429_CR48","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.1523\/JNEUROSCI.5539-03.2004","volume":"24","author":"NJ Allen","year":"2004","unstructured":"Allen NJ, Rossi DJ, Attwell D. Sequential release of GABA by exocytosis and reversed uptake leads to neuronal swelling in simulated ischemia of hippocampal slices. J Neurosci. 2004;24:3837\u201349.","journal-title":"J Neurosci"},{"key":"1429_CR49","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1523\/JNEUROSCI.07-02-00357.1987","volume":"7","author":"DW Choi","year":"1987","unstructured":"Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neurotoxicity in cortical cell culture. J Neurosci. 1987;7:357\u201368.","journal-title":"J Neurosci"},{"key":"1429_CR50","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/ana.20741","volume":"59","author":"VE O\u2019Collins","year":"2006","unstructured":"O\u2019Collins VE, Macleod MR, Donnan GA, Horky LL, Van Der Worp BH, Howells DW. 1026 Experimental treatments in acute stroke. Ann Neurol. 2006;59:467\u201377.","journal-title":"Ann Neurol"},{"key":"1429_CR51","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1177\/0271678X18771440","volume":"38","author":"A Klass","year":"2018","unstructured":"Klass A, S\u00e1nchez-Porras R, Santos E. Systematic review of the pharmacological agents that have been tested against spreading depolarizations. J Cereb Blood Flow Metab. 2018;38:1149\u201379.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR52","unstructured":"Andrew RD. The dogma of glutamate excitotoxicity as a major cause of stroke damage: an alternate target. In: Abstract 60010 2004 Neuroscience meeting planner. San Diego: Society for Neuroscience. 2004 Online."},{"key":"1429_CR53","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1750-3639.1994.tb00808.x","volume":"4","author":"K-A Hossmann","year":"1994","unstructured":"Hossmann K-A. Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised. Brain Pathol. 1994;4:23\u201336.","journal-title":"Brain Pathol"},{"key":"1429_CR54","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1474-4422(02)00164-3","volume":"1","author":"C Ikonomidou","year":"2002","unstructured":"Ikonomidou C, Turski L. Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol. 2002;1:383\u20136.","journal-title":"Lancet Neurol"},{"key":"1429_CR55","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0736-5748(99)00096-9","volume":"18","author":"TP Obrenovitch","year":"2000","unstructured":"Obrenovitch TP, Urenjak J, Zilkha E, Jay TM. Excitotoxicity in neurological disorders\u2014the glutamate paradox. Int J Dev Neurosci. 2000;18:281\u20137.","journal-title":"Int J Dev Neurosci"},{"key":"1429_CR56","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/j.1471-4159.1959.tb12636.x","volume":"3","author":"A van Harreveld","year":"1959","unstructured":"van Harreveld A. Compounds in brain extracts causing spreading depression of cerebral cortical activity and contraction of crustacean muscle. J Neurochem. 1959;3:300\u201315.","journal-title":"J Neurochem"},{"key":"1429_CR57","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1152\/jn.00817.2010","volume":"105","author":"HA Douglas","year":"2011","unstructured":"Douglas HA, Callaway JK, Sword J, Kirov SA, Andrew RD. Potent inhibition of anoxic depolarization by the sodium channel blocker dibucaine. J Neurophysiol. 2011;105:1482\u201394.","journal-title":"J Neurophysiol"},{"key":"1429_CR58","doi-asserted-by":"crossref","first-page":"e22351","DOI":"10.1371\/journal.pone.0022351","volume":"6","author":"WC Risher","year":"2011","unstructured":"Risher WC, Lee MR, Fomitcheva IV, Hess DC, Kirov SA. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex. PLoS ONE. 2011;6:e22351.","journal-title":"PLoS ONE"},{"key":"1429_CR59","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1152\/jn.00701.2011","volume":"107","author":"SH White","year":"2012","unstructured":"White SH, Brisson CD, Andrew RD. Examining protection from anoxic depolarization by the drugs dibucaine and carbetapentane using whole cell recording from CA1 neurons. J Neurophysiol. 2012;107:2083\u201395.","journal-title":"J Neurophysiol"},{"key":"1429_CR60","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S0006-8993(96)01094-3","volume":"745","author":"D Ashton","year":"1997","unstructured":"Ashton D, Willems R, Wynants J, Van Reempts J, Marrannes R, Clincke G. Altered Na+-channel function as an in vitro model of the ischemic penumbra: action of lubeluzole and other neuroprotective drugs. Brain Res. 1997;745:210\u201321.","journal-title":"Brain Res"},{"key":"1429_CR61","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1152\/jn.00321.2002","volume":"88","author":"TR Anderson","year":"2002","unstructured":"Anderson TR, Andrew RD. Spreading depression: imaging and blockade in the rat neocortical brain slice. J Neurophysiol. 2002;88:2713\u201325.","journal-title":"J Neurophysiol"},{"key":"1429_CR62","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1152\/jn.2000.84.4.1869","volume":"84","author":"M Muller","year":"2000","unstructured":"Muller M, Somjen GG. Na(+) dependence and the role of glutamate receptors and Na(+) channels in ion fluxes during hypoxia of rat hippocampal slices. J Neurophysiol. 2000;84:1869\u201380.","journal-title":"J Neurophysiol"},{"key":"1429_CR63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neures.2020.03.003","volume":"164","author":"H Toyoda","year":"2020","unstructured":"Toyoda H, Kawano T, Sato H, Kato T. Cellular mechanisms underlying the rapid depolarization caused by oxygen and glucose deprivation in layer III pyramidal cells of the somatosensory cortex. Neurosci Res. 2020;164:1\u20139.","journal-title":"Neurosci Res"},{"key":"1429_CR64","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1152\/jn.1997.78.2.903","volume":"78","author":"S Yamamoto","year":"1997","unstructured":"Yamamoto S, Tanaka E, Shoji Y, Kudo Y, Inokuchi H, Higashi H. Factors that reverse the persistent depolarization produced by deprivation of oxygen and glucose in rat hippocampal CA1 neurons in vitro. J Neurophysiol. 1997;78:903\u201311.","journal-title":"J Neurophysiol"},{"key":"1429_CR65","doi-asserted-by":"crossref","first-page":"S248","DOI":"10.1139\/y92-268","volume":"70","author":"GG Somjen","year":"1992","unstructured":"Somjen GG, Aitken PG, Czeh GL, Herreras O, Jing J, Young JN. Mechanisms of spreading depression\u2014a review of recent findings and a hypothesis. Can J Physiol Pharmacol. 1992;70:S248\u201354.","journal-title":"Can J Physiol Pharmacol"},{"key":"1429_CR66","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1113\/jphysiol.1989.sp017690","volume":"414","author":"BYM Andreasen","year":"1989","unstructured":"Andreasen BYM, Lambert JDC, Jensen MS. Effects of new non-N-methyl-d-aspartate antagonists on synaptic transmission in the in vitro rat hippocampus. J Physiol. 1989;414:317\u201336.","journal-title":"J Physiol"},{"key":"1429_CR67","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/j.1476-5381.1996.tb15245.x","volume":"117","author":"T Frankiewicz","year":"1996","unstructured":"Frankiewicz T, Potier B, Bashir ZI, Collingridge GL, Parsons CG. Effects of memantine and MK-801 on NMDA-induced currents in cultureepolares and on synaptic transmission and LTP in area CA1 of rat hippocampal slices. Br J Pharmacol. 1996;117:689\u201397.","journal-title":"Br J Pharmacol"},{"key":"1429_CR68","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1469-7793.2001.t01-1-00123.x","volume":"534","author":"DG Placantonakis","year":"2001","unstructured":"Placantonakis DG, Welsh JP. Two distinct oscillatory states determined by the NMDA receptor in rat inferior olive. J Physiol. 2001;534:123\u201340.","journal-title":"J Physiol"},{"key":"1429_CR69","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1111\/j.1476-5381.1990.tb14169.x","volume":"101","author":"TW Stone","year":"1990","unstructured":"Stone TW. Sensitivity of hippocampaepolares to kainic acid, and antagonism by kynurenate. Br J Pharmacol. 1990;101:847\u201352.","journal-title":"Br J Pharmacol"},{"key":"1429_CR70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(98)00812-9","volume":"812","author":"M M\u00fcller","year":"1998","unstructured":"M\u00fcller M, Somjen GG. Inhibition of major cationic inward currents prevents spreading depression-like hypoxic depolarization in rat hippocampal tissue slices. Brain Res. 1998;812:1\u201313.","journal-title":"Brain Res"},{"key":"1429_CR71","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.nbd.2016.07.019","volume":"95","author":"O Revah","year":"2016","unstructured":"Revah O, Lasser-Katz E, Fleidervish IA, Gutnick MJ. The earliest neuronal responses to hypoxia in the neocortical circuit are glutamate-dependent. Neurobiol Dis. 2016;95:158\u201367.","journal-title":"Neurobiol Dis"},{"key":"1429_CR72","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s12028-019-00777-6","volume":"32","author":"R Helbok","year":"2019","unstructured":"Helbok R, Hartings JA, Schiefecker A, Balan\u00e7a B, Jewel S, Foreman B, et al. What should a clinician do when spreading depolarizations are observed in a patient? Neurocrit Care. 2019;32:306\u201310.","journal-title":"Neurocrit Care"},{"key":"1429_CR73","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1038\/jcbfm.2014.136","volume":"34","author":"Z Bere","year":"2014","unstructured":"Bere Z, Obrenovitch TP, Koz\u00e1k G, Bari F, Farkas E. Imaging reveals the focal area of spreading depolarizations and a variety of hemodynamic responses in a rat microembolic stroke model. J Cereb Blood Flow Metab. 2014;34:1695\u2013705.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR74","doi-asserted-by":"crossref","first-page":"e96585","DOI":"10.1371\/journal.pone.0096585","volume":"9","author":"CD Brisson","year":"2014","unstructured":"Brisson CD, Hsieh YT, Kim D, Jin AY, Andrew RD. Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state. PLoS ONE. 2014;9:e96585.","journal-title":"PLoS ONE"},{"key":"1429_CR75","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0304-3940(92)90549-M","volume":"139","author":"RJ Radek","year":"1992","unstructured":"Radek RJ, Giardina WJ. The neuroprotective effects of dextromethorphan on guinea pig-derived hippocampal slices during hypoxia. Neurosci Lett. 1992;139:191\u20133.","journal-title":"Neurosci Lett"},{"key":"1429_CR76","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1152\/jn.1998.80.5.2378","volume":"80","author":"G Erdemli","year":"1998","unstructured":"Erdemli G, Xu YZ, Krnjevi\u0107 K. Potassium conductance causing hyperpolarization of CA1 hippocampal neurons during hypoxia. J Neurophysiol. 1998;80:2378\u201390.","journal-title":"J Neurophysiol"},{"key":"1429_CR77","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1152\/jn.01145.2004","volume":"94","author":"S Canals","year":"2005","unstructured":"Canals S, Makarova I, L\u00f3pez-Aguado L, Largo C, Ibarz JM, Herreras O. Longitudinal depolarization gradients along the somatodendritic axis of CA1 pyramidal cells: a novel feature of spreading depression. J Neurophysiol. 2005;94:943\u201351.","journal-title":"J Neurophysiol"},{"key":"1429_CR78","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/348443a0","volume":"348","author":"M Szatkowski","year":"1990","unstructured":"Szatkowski M, Barbour B, Attwell D. Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature. 1990;348:443\u20136.","journal-title":"Nature"},{"key":"1429_CR79","doi-asserted-by":"crossref","first-page":"7189","DOI":"10.1523\/JNEUROSCI.18-18-07189.1998","volume":"18","author":"TA Basarsky","year":"1998","unstructured":"Basarsky TA, Duffy SN, Andrew RD, MacVicar BA. Imaging spreading depression and associated intracellular calcium waves in brain slices. J Neurosci Off J Soc Neurosci. 1998;18:7189\u201399.","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"1429_CR80","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1093\/cercor\/bhq018","volume":"20","author":"N Zhou","year":"2010","unstructured":"Zhou N, Gordon GRJ, Feighan D, MacVicar BA. Transient swelling, acidification, and mitochondrial depolarization occurs in neurons but not astrocytes during spreading depression. Cereb Cortex. 2010;20:2614\u201324.","journal-title":"Cereb Cortex"},{"key":"1429_CR81","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1523\/JNEUROSCI.21-13-04600.2001","volume":"21","author":"IA Fleidervish","year":"2001","unstructured":"Fleidervish IA, Gebhardt C, Astman N, Gutnick MJ, Heinemann U. Enhanced spontaneous transmitter release is the earliest consequence of neocortical hypoxia that can explain the disruption of normal circuit function. J Neurosci Off J Soc Neurosci. 2001;21:4600\u20138.","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"1429_CR82","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1172\/JCI71886","volume":"124","author":"FN Soria","year":"2014","unstructured":"Soria FN, P\u00e9rez-Samart\u00edn A, Martin A, Gona KB, Llop J, Szczupak B, et al. Extrasynaptic glutamate release through cystine\/glutamate antiporter contributes to ischemic damage. J Clin Investig. 2014;124:3645\u201355.","journal-title":"J Clin Investig"},{"key":"1429_CR83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/glia.23874","volume":"68","author":"H Aizawa","year":"2020","unstructured":"Aizawa H, Sun W, Sugiyama K, Itou Y, Aida T, Cui W, et al. Glial glutamate transporter GLT-1 determines susceptibility to spreading depression in the mouse cerebral cortex. Glia. 2020;68:1\u201312.","journal-title":"Glia"},{"key":"1429_CR84","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/jcbfm.2013.113","volume":"33","author":"N Zhou","year":"2013","unstructured":"Zhou N, Rungta RL, Malik A, Han H, Wu DC, MacVicar BA. Regenerative glutamate release by presynaptic NMDA receptors contributes to spreading depression. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2013;33:1582\u201394.","journal-title":"J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"key":"1429_CR85","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1093\/cercor\/bhv054","volume":"25","author":"R Enger","year":"2015","unstructured":"Enger R, Tang W, Vindedal GF, Jensen V, Helm PJ, Sprengel R, et al. Dynamics of ionic shifts in cortical spreading depression. Cereb Cortex. 2015;25:4469\u201376.","journal-title":"Cereb Cortex"},{"key":"1429_CR86","doi-asserted-by":"crossref","first-page":"967","DOI":"10.15252\/emmm.201505944","volume":"8","author":"C Capuani","year":"2016","unstructured":"Capuani C, Melone M, Tottene A, Bragina L, Crivellaro G, Santello M, et al. Defective glutamate and K+ clearance by cortical astrocytes in familial hemiplegic migraine type 2. EMBO Mol Med. 2016;8:967\u201386.","journal-title":"EMBO Mol Med"},{"key":"1429_CR87","doi-asserted-by":"crossref","first-page":"105071","DOI":"10.1016\/j.nbd.2020.105071","volume":"145","author":"Y-Y Mei","year":"2020","unstructured":"Mei Y-Y, Lee M-H, Cheng T-C, Hsiao I-H, Wu DC, Zhou N. NMDA receptors sustain but do not initiate neuronal depolarization in spreading depolarization. Neurobiol Dis. 2020;145:105071.","journal-title":"Neurobiol Dis"},{"key":"1429_CR88","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/35002090","volume":"403","author":"DJ Rossi","year":"2000","unstructured":"Rossi DJ, Oshima T, Attwell D. Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature. 2000;403:316\u201321.","journal-title":"Nature"},{"key":"1429_CR89","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/PL00005161","volume":"357","author":"TP Obrenovitch","year":"1998","unstructured":"Obrenovitch TP, Zilkha E, Urenjak J. Effects of pharmacological inhibition of glutamate-uptake on ischaemia-induced glutamate efflux and anoxic depolarization latency. Naunyn-Schmiedeberg\u2019s Arch Pharmacol. 1998;357:225\u201331.","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"key":"1429_CR90","doi-asserted-by":"publisher","first-page":"e0186243","DOI":"10.1371\/journal.pone.0186243","volume":"12","author":"W Krzy\u017canowska","year":"2017","unstructured":"Krzy\u017canowska W, Pomierny B, Bystrowska B, Pomierny-Chamio\u0142o L, Filip M, Budziszewska B, et al. Ceftriaxone- and N-acetylcysteine-induced brain tolerance to ischemia: influence on glutamate levels in focal cerebral ischemia. PLoS ONE. 2017;12:e0186243. https:\/\/doi.org\/10.1371\/journal.pone.0186243.","journal-title":"PLoS ONE"},{"key":"1429_CR91","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1152\/jn.1996.76.4.2707","volume":"76","author":"RD Andrew","year":"1996","unstructured":"Andrew RD, Adams JR, Polischuk TM. Imaging NMDA-anepolarte-induced intrinsic optical signals from the hippocampal slice. J Neurophysiol. 1996;76:2707\u201317.","journal-title":"J Neurophysiol"},{"key":"1429_CR92","doi-asserted-by":"crossref","first-page":"179, 185\u2013196","DOI":"10.1006\/meth.1999.0771","volume":"18","author":"RD Andrew","year":"1999","unstructured":"Andrew RD, Jarvis CR, Obeidat AS. Potential sources of intrinsic optical signals imaged in live brain slices. Methods (San Diego, Calif). 1999;18:179, 185\u201396.","journal-title":"Methods (San Diego, Calif)"},{"key":"1429_CR93","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1046\/j.1460-9568.1998.00358.x","volume":"10","author":"AS Obeidat","year":"1998","unstructured":"Obeidat AS, Andrew RD. Spreading depression determines acute cellular damage in the hippocampal slice during oxygen\/glucose deprivation. Eur J Neurosci. 1998;10:3451\u201361.","journal-title":"Eur J Neurosci"},{"key":"1429_CR94","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1006\/nbdi.1998.0172","volume":"4","author":"TM Polischuk","year":"1998","unstructured":"Polischuk TM, Jarvis CR, Andrew RD. Intrinsic optical signaling denoting neuronal damage in response to acute excitotoxic insult by domoic acid in the hippocampal slice. Neurobiol Dis. 1998;4:423\u201337.","journal-title":"Neurobiol Dis"},{"key":"1429_CR95","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2015.03.029","volume":"161","author":"RL Rungta","year":"2015","unstructured":"Rungta RL, Choi HB, Tyson JR, Malik A, Dissing-Olesen L, Lin PJC, et al. The cellular mechanisms of neuronal swelling underlying cytotoxic edema. Cell. 2015;161:610\u201321.","journal-title":"Cell"},{"key":"1429_CR96","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0006-8993(93)91412-L","volume":"610","author":"O Herreras","year":"1993","unstructured":"Herreras O, Somjen GG. Analysis of potential shifts associated with recurrent spreading depression and prolonged unstable spreading depression induced by microdialysis of elevated K+ in hippocampus of anesthetized rats. Brain Res. 1993;610:283\u201394.","journal-title":"Brain Res"},{"key":"1429_CR97","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrn3770","volume":"15","author":"D Pietrobon","year":"2014","unstructured":"Pietrobon D, Moskowitz MA. Chaos and commotion in the wake of cortical spreading depression and spreading depolarizations. Nat Rev Neurosci. 2014;15:379\u201393.","journal-title":"Nat Rev Neurosci"},{"key":"1429_CR98","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1089\/neu.2005.22.277","volume":"22","author":"AJ Church","year":"2005","unstructured":"Church AJ, Andrew RD. Spreading depression expands traumatic injury in neocortical brain slices. J Neurotrauma. 2005;22:277\u201390.","journal-title":"J Neurotrauma"},{"key":"1429_CR99","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/dev.420100402","volume":"10","author":"B De Luca","year":"1977","unstructured":"De Luca B, Bure\u0161 J. Development of cortical spreading depression and of its transition to the caudate nucleus in rats. Dev Psychobiol. 1977;10:289\u201397.","journal-title":"Dev Psychobiol"},{"key":"1429_CR100","doi-asserted-by":"crossref","first-page":"12172","DOI":"10.1523\/JNEUROSCI.0400-15.2015","volume":"35","author":"AB Steffensen","year":"2015","unstructured":"Steffensen AB, Sword J, Croom D, Kirov SA, MacAulay N. Chloride cotransporters as a molecular mechanism underlying spreading depolarization-induced dendritic beading. J Neurosci. 2015;35:12172\u201387.","journal-title":"J Neurosci"},{"key":"1429_CR101","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nn.4236","volume":"19","author":"NL Weilinger","year":"2016","unstructured":"Weilinger NL, Lohman AW, Rakai BD, Ma EMM, Bialecki J, Maslieieva V, et al. Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity. Nat Neurosci. 2016;19:432\u201342.","journal-title":"Nat Neurosci"},{"key":"1429_CR102","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/ana.25147","volume":"83","author":"JP Dreier","year":"2018","unstructured":"Dreier JP, Major S, Foreman B, Winkler MKL, Kang E-J, Milakara D, et al. Terminal spreading depolarization and electric silence in death of human cortex. Ann Neurol. 2018;83:295\u2013310.","journal-title":"Ann Neurol"},{"key":"1429_CR103","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1093\/brain\/aws152","volume":"135","author":"DN Hertle","year":"2012","unstructured":"Hertle DN, Dreier JP, Woitzik J, Hartings JA, Bullock R, Okonkwo DO, et al. Effect of analgesics and sedatives on the occurrence of spreading depolarizations accompanying acute brain injury. Brain. 2012;135:2390\u20138.","journal-title":"Brain"},{"key":"1429_CR104","first-page":"e519","volume":"40","author":"OW Sakowitz","year":"2009","unstructured":"Sakowitz OW, Kiening KL, Krajewski KL, Sarrafzadeh AS, Fabricius M, Strong AJ, et al. Preliminary evidence that ketamine inhibits spreading depolarizations in acute human brain injury. Stroke U S. 2009;40:e519\u201322.","journal-title":"Stroke U S"},{"key":"1429_CR105","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1186\/s13054-019-2711-3","volume":"23","author":"E Santos","year":"2019","unstructured":"Santos E, Olivares-Rivera A, Major S, S\u00e1nchez-Porras R, Uhlmann L, Kunzmann K, et al. Lasting s-ketamine block of spreading depolarizations in subarachnoid hemorrhage: a retrospective cohort study. Crit Care. 2019;23:427.","journal-title":"Crit Care"},{"key":"1429_CR106","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1177\/0271678X16671317","volume":"36","author":"E Santos","year":"2016","unstructured":"Santos E, Le\u00f3n F, Silos H, Sanchez-Porras R, Shuttleworth CW, Unterberg A, et al. Incidence, hemodynamic, and electrical characteristics of spreading depolarization in a swine model are affected by local but not by intravenous application of magnesium. J Cereb Blood Flow Metab. 2016;36:2051\u20137.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR107","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1186\/s13054-020-03004-3","volume":"24","author":"PM Honore","year":"2020","unstructured":"Honore PM, Mugisha A, Kugener L, Redant S, Attou R, Gallerani A, et al. High doses of ketamine to improve neuronal edema in subarachnoid hemorrhage: we\u00a0should consider other undesirable organ targets. Crit Care (London, England). 2020;24:362.","journal-title":"Crit Care (London, England)."},{"key":"1429_CR108","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.wneu.2016.09.121","volume":"97","author":"C Von der Brelie","year":"2017","unstructured":"Von der Brelie C, Seifert M, Rot S, Tittel A, Sanft C, Meier U, et al. Sedation of patients with acute aneurysmal subarachnoid hemorrhage with ketamine is safe and might influence the occurrence of cerebral infarctions associated with delayed cerebral ischemia. World Neurosurg U S. 2017;97:374\u201382.","journal-title":"World Neurosurg U S"},{"key":"1429_CR109","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.expneurol.2018.04.007","volume":"305","author":"KM Reinhart","year":"2018","unstructured":"Reinhart KM, Shuttleworth CW. Ketamine reduces deleterious consequences of spreading depolarizations. Exp Neurol U S. 2018;305:121\u20138.","journal-title":"Exp Neurol U S"},{"key":"1429_CR110","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20915801","author":"K Schoknecht","year":"2020","unstructured":"Schoknecht K, Kikhia M, Lemale CL, Liotta A, Lublinsky S, Mueller S, et al. The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model. J Cereb Blood Flow Metab. 2020. https:\/\/doi.org\/10.1177\/0271678X20915801.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR111","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/0006-8993(90)91060-T","volume":"527","author":"U Dirnagl","year":"1990","unstructured":"Dirnagl U, Tanabe J, Pulsinelli W. Pre- and post-treatment with MK-801 but not pretreatment alone reduces neocortical damage after focal cerebral ischemia in the rat. Brain Res. 1990;527:62\u20138.","journal-title":"Brain Res"},{"key":"1429_CR112","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/jcbfm.1992.54","volume":"12","author":"R Gill","year":"1992","unstructured":"Gill R, Andin\u00e9 P, Hillered L, Persson L, Hagberg H. The effect of MK-801 on cortical spreading depression in the penumbral zone\u00a0following focal ischaemia in the rat. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 1992;12:371\u20139.","journal-title":"J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"key":"1429_CR113","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/jcbfm.1992.103","volume":"12","author":"T Iijima","year":"1992","unstructured":"Iijima T, Mies G, Hossmann KA. Repeated negative DC deflections in rat cortex following middle cerebral artery\u00a0occlusion are abolished by MK-801: effect on volume of ischemic injury. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 1992;12:727\u201333.","journal-title":"J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"key":"1429_CR114","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/brain\/awf007","volume":"125","author":"JP Dreier","year":"2002","unstructured":"Dreier JP, Kleeberg J, Petzold G, Priller J, Windm\u00fcller O, Orzechowski H-D, et al. Endothelin-1 potently induces Le\u00e3o\u2019s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura? Brain J Neurol. 2002;125:102\u201312.","journal-title":"Brain J Neurol"},{"key":"1429_CR115","doi-asserted-by":"crossref","first-page":"3710","DOI":"10.1073\/pnas.93.8.3710","volume":"93","author":"VI Koroleva","year":"1996","unstructured":"Koroleva VI, Bures J. The use of spreading depression waves for acute and long-term monitoring of the penumbra zone of focal ischemic damage in rats. Proc Natl Acad Sci U S A. 1996;93:3710\u20134.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1429_CR116","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/0006-8993(88)90690-7","volume":"457","author":"R Marrannes","year":"1988","unstructured":"Marrannes R, Willems R, De Prins E, Wauquier A. Evidence for a role of the N-methyl-d-aspartate (NMDA) receptor in cortical spreading depression in the rat. Brain Res. 1988;457:226\u201340.","journal-title":"Brain Res"},{"key":"1429_CR117","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1177\/0271678X16646586","volume":"37","author":"R S\u00e1nchez-Porras","year":"2017","unstructured":"S\u00e1nchez-Porras R, Santos E, Sch\u00f6ll M, Kunzmann K, Stock C, Silos H, et al. Ketamine modulation of the haemodynamic response to spreading depolarization in the gyrencephalic swine brain. J Cereb Blood Flow Metab. 2017;37:1720\u201334.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR118","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/0006-8993(87)91652-0","volume":"437","author":"J Hern\u00e1nd\u00e9z-C\u00e1ceres","year":"1987","unstructured":"Hern\u00e1nd\u00e9z-C\u00e1ceres J, Macias-Gonz\u00e1lez R, Bro\u017eek G, Bure\u0161 J, Hernandez-Caceres J, Macias-Gonzalez R, et al. Systemic ketamine blocks cortical spreading depression but does not delay the onset of terminal anoxic depolarization in rats. Brain Res. 1987;437:360\u20134.","journal-title":"Brain Res"},{"key":"1429_CR119","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/jcbfm.1992.32","volume":"12","author":"M Lauritzen","year":"1992","unstructured":"Lauritzen M, Hansen AJ. The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab. 1992;12:223\u20139.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR120","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1001\/jamaneurol.2019.4476","volume":"77","author":"JA Hartings","year":"2020","unstructured":"Hartings JA, Andaluz N, Bullock MR, Hinzman JM, Mathern B, Pahl C, et al. Prognostic value of spreading depolarizations in patients with severe traumatic brain injury. JAMA Neurol. 2020;77:489\u201399.","journal-title":"JAMA Neurol"},{"key":"1429_CR121","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1097\/WNP.0000000000000274","volume":"33","author":"C Drenckhahn","year":"2016","unstructured":"Drenckhahn C, Windler C, Major S, Kang E-J, Scheel M, Vajkoczy P, et al. Complications in aneurysmal subarachnoid hemorrhage patients with and without subdural electrode strip for electrocorticography. J Clin Neurophysiol. 2016;33:250\u20139.","journal-title":"J Clin Neurophysiol"},{"key":"1429_CR122","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1089\/neu.1997.14.677","volume":"14","author":"TP Obrenovitch","year":"1997","unstructured":"Obrenovitch TP, Urenjak J. Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury? J Neurotrauma. 1997;14:677\u201398.","journal-title":"J Neurotrauma"},{"key":"1429_CR123","first-page":"4","volume":"12","author":"M Verity","year":"1991","unstructured":"Verity M. Use and abuse of tissue cultures in neurotoxicity studies. Neurotoxicology. 1991;12:4\u2013459.","journal-title":"Neurotoxicology"},{"key":"1429_CR124","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/0006-8993(93)91411-K","volume":"610","author":"O Herreras","year":"1993","unstructured":"Herreras O, Somjen GG. Propagation of spreading depression among dendrites and somata of the same cell population. Brain Res. 1993;610:276\u201382.","journal-title":"Brain Res"},{"key":"1429_CR125","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0006-8993(91)90132-F","volume":"557","author":"J Jing","year":"1991","unstructured":"Jing J, Aitken PG, Somjen GG. Lasting neuron depression induced by high potassium and its prevention by low calcium and NMDA receptor blockade. Brain Res. 1991;557:177\u201383.","journal-title":"Brain Res"},{"key":"1429_CR126","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1097\/00004647-199609000-00016","volume":"16","author":"TP Obrenovitch","year":"1996","unstructured":"Obrenovitch TP, Zilkha E, Urenjak J. Evidence against high extracellular glutamate promoting the elicitation of spreading depression by potassium. J Cereb Blood Flow Metab. 1996;16:923\u201331.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR127","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.expneurol.2015.03.014","volume":"267","author":"JM Hinzman","year":"2015","unstructured":"Hinzman JM, DiNapoli VA, Mahoney EJ, Gerhardt GA, Hartings JA. Spreading depolarizations mediate excitotoxicity in the development of acute cortical lesions. Exp Neurol. 2015;267:243\u201353.","journal-title":"Exp Neurol"},{"key":"1429_CR128","doi-asserted-by":"crossref","first-page":"8014","DOI":"10.1523\/JNEUROSCI.0765-08.2008","volume":"28","author":"RM Dietz","year":"2008","unstructured":"Dietz RM, Weiss JH, Shuttleworth CW. Zn2+ influx is critical for some forms of spreading depression in brain slices. J Neurosci. 2008;28:8014\u201324.","journal-title":"J Neurosci"},{"key":"1429_CR129","doi-asserted-by":"crossref","first-page":"9888","DOI":"10.1523\/JNEUROSCI.23-30-09888.2003","volume":"23","author":"O Peters","year":"2003","unstructured":"Peters O, Schipke CG, Hashimoto Y, Kettenmann H. Different mechanisms promote astrocyte Ca2+ waves and spreading depression in the mouse neocortex. J Neurosci Off J Soc Neurosci. 2003;23:9888\u201396.","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"1429_CR130","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1177\/1073858412453340","volume":"19","author":"JP Dreier","year":"2013","unstructured":"Dreier JP, Isele T, Reiffurth C, Offenhauser N, Kirov SA, Dahlem MA, et al. Is spreading depolarization characterized by an abrupt, massive release of Gibbs free energy from the human brain cortex? Neuroscientist. 2013;19:25\u201342.","journal-title":"Neuroscientist"},{"key":"1429_CR131","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/0306-4522(78)90122-7","volume":"3","author":"P Kraig","year":"1978","unstructured":"Kraig P, Nicholson C. Extracellular ionic variations during spreading depression. Neuroscience. 1978;3:1045\u201359.","journal-title":"Neuroscience"},{"key":"1429_CR132","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1161\/STROKEAHA.112.672352","volume":"44","author":"OW Sakowitz","year":"2013","unstructured":"Sakowitz OW, Santos E, Nagel A, Krajewski KL, Hertle DN, Vajkoczy P, et al. Clusters of spreading depolarizations are associated with disturbed cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2013;44:220\u20133.","journal-title":"Stroke"},{"key":"1429_CR133","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/1911010a0","volume":"191","author":"DR Watkins","year":"1961","unstructured":"Watkins DR, Curtis JC. Analogues of glutamic and \u03b3-amino-n-butyric acids having potent actions on mammalian neurones. Nature. 1961;191:1010\u20131.","journal-title":"Nature"},{"key":"1429_CR134","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/j.1469-7793.1999.00797.x","volume":"520","author":"J Keelan","year":"1999","unstructured":"Keelan J, Vergun O, Duchen MR. Excitotoxic mitochondriaepolarizationon requires both calcium and nitric oxide in rat hippocampal neurons. J Physiol. 1999;520:797\u2013813.","journal-title":"J Physiol"},{"key":"1429_CR135","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.bbabio.2016.04.003","volume":"1857","author":"CB Rueda","year":"2016","unstructured":"Rueda CB, Llorente-Folch I, Traba J, Amigo I, Gonzalez-Sanchez P, Contreras L, et al. Glutamate excitotoxicity and Ca2+-regulation of respiration: role of the Ca2+ activated mitochondrial transporters (CaMCs). Biochim Biophys Act Bioenerg. 2016;1857:1158\u201366.","journal-title":"Biochim Biophys Act Bioenerg"},{"key":"1429_CR136","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000056066","volume":"62","author":"H-B Jiang","year":"2001","unstructured":"Jiang H-B, Yoneyama H, Furukawa A, Hamamoto T, Takahara JIY. Effect of isosorbide dinitrate on nitric oxide synthase under hypoxia. Pharmacology. 2001;62:10\u20136.","journal-title":"Pharmacology"},{"key":"1429_CR137","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1089\/089771502760342009","volume":"19","author":"S Uetsuka","year":"2002","unstructured":"Uetsuka S, Fujisawa H, Yasuda H, Shima H, Suzuki M. Severe cerebral blood flow reduction inhibits nitric oxide synthesis. J Neurotrauma. 2002;19:1105\u201316.","journal-title":"J Neurotrauma"},{"key":"1429_CR138","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/00004647-199802000-00011","volume":"18","author":"O Peters","year":"1998","unstructured":"Peters O, Back T, Lindauer U, Busch C, Megow D, Dreier J, et al. Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab. 1998;18:196\u2013205.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR139","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1074\/jbc.M109.053058","volume":"285","author":"C Kubota","year":"2010","unstructured":"Kubota C, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, et al. Constitutive reactive oxygen species generation from autophagosome\/lysosome in neuronal oxidative toxicity. J Biol Chem. 2010;285:667\u201374.","journal-title":"J Biol Chem"},{"key":"1429_CR140","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1001\/jama.2015.7851","volume":"314","author":"S Prabhakaran","year":"2015","unstructured":"Prabhakaran S, Ruff I, Bernstein RA. Intervention for acute stroke\u2014reply. JAMA. 2015;314:626\u20137.","journal-title":"JAMA"},{"key":"1429_CR141","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnins.2015.00469","volume":"9","author":"J Lewerenz","year":"2015","unstructured":"Lewerenz J, Maher P. Chronic glutamate toxicity in neurodegenerative diseases\u2014what is the evidence? Front Neurosci. 2015;9:1\u201320.","journal-title":"Front Neurosci"},{"key":"1429_CR142","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnins.2019.00304","volume":"13","author":"A Benussi","year":"2019","unstructured":"Benussi A, Alberici A, Buratti E, Ghidoni R, Gardoni F, Di LM, et al. Toward a glutamate hypothesis of frontotemporal dementia. Front Neurosci. 2019;13:1\u20139.","journal-title":"Front Neurosci"},{"key":"1429_CR143","volume-title":"Huntington\u2019s disease\u2014molecular pathogenesis and current models","author":"M Anglada-Huguet","year":"2017","unstructured":"Anglada-Huguet M, Vidal-Sancho L, Cabezas-Llobet N, Alberch J, Xifr\u00f3 X. Pathogenesis of Huntington\u2019s disease: how to fight excitotoxicity and transcriptional dysregulation. In: Tunali NE, editor. Huntington\u2019s disease\u2014molecular pathogenesis and current models. London: InTech; 2017."},{"key":"1429_CR144","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0198116","volume":"13","author":"H Blasco","year":"2018","unstructured":"Blasco H, Patin F, Descat A, Gar\u00e7on G, Corcia P, Gel\u00e9 P, et al. A pharmaco-metabolomics approach in a clinical trial of ALS: identification of predictive markers of progression. PLoS ONE. 2018;13:1\u201314.","journal-title":"PLoS ONE"},{"key":"1429_CR145","first-page":"1190","volume":"14","author":"K Ahmad","year":"2017","unstructured":"Ahmad K, Baig MH, Mushtaq G, Kamal MA, Greig NH, Choi I. Commonalities in biological pathways, genetics, and cellular mechanism between Alzheimer disease and other neurodegenerative diseases: an in silico-updated overview. Curr Alzheimer Res. 2017;14:1190\u20137.","journal-title":"Curr Alzheimer Res"},{"key":"1429_CR146","doi-asserted-by":"crossref","first-page":"464","DOI":"10.3390\/biom10030464","volume":"10","author":"T Hanada","year":"2020","unstructured":"Hanada T. Ionotropic glutamate receptors in epilepsy: a review focusing on AMPA and NMDA receptors. Biomolecules. 2020;10:464.","journal-title":"Biomolecules"},{"key":"1429_CR147","doi-asserted-by":"crossref","first-page":"102069","DOI":"10.1016\/j.nicl.2019.102069","volume":"24","author":"JP Nicolo","year":"2019","unstructured":"Nicolo JP, O\u2019Brien TJ, Kwan P. Role of cerebral glutamate in post-stroke epileptogenesis. NeuroImage Clin. 2019;24:102069.","journal-title":"NeuroImage Clin"},{"key":"1429_CR148","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1097\/00004647-200112000-00010","volume":"21","author":"A H\u00e5berg","year":"2001","unstructured":"H\u00e5berg A, Qu H, S\u00e6ther O, Unsg\u00e5rd G, Haraldseth O, Sonnewald U. Differences in neurotransmitter synthesis and intermediary metabolism between glutamatergic and GABAergic neurons during 4 h of middle cerebral artery occlusion in the rat: the role of astrocytes in neuronal survival. J Cereb Blood Flow Metab. 2001;21:1451\u201363.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1429_CR149","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3171\/2009.12.JNS09689","volume":"23","author":"R Chamoun","year":"2010","unstructured":"Chamoun R, Suki D, Gopinath SP, Goodman JC, Robertson C. Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury. J Neurosurg. 2010;23:564\u201370.","journal-title":"J Neurosurg"},{"key":"1429_CR150","first-page":"11","volume":"2012","author":"C Willis","year":"2012","unstructured":"Willis C, Lybrand S, Bellamy N. Excitatory amino acid inhibitors for traumatic brain injury. Cochrane Database Syst Rev. 2012;2012:11\u20135.","journal-title":"Cochrane Database Syst Rev"},{"key":"1429_CR151","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1089\/neu.2018.6203","volume":"37","author":"PM Kochanek","year":"2020","unstructured":"Kochanek PM, Jackson TC, Jha RM, Clark RSB, Okonkwo DO, Baylr H, et al. Paths to successful translation of new therapies for severe traumatic brain injury in the golden age of traumatic brain injury research: a Pittsburgh vision. J Neurotrauma. 2020;37:2353\u201371.","journal-title":"J Neurotrauma"},{"key":"1429_CR152","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.pneurobio.2013.11.006","volume":"115","author":"TW Lai","year":"2014","unstructured":"Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke: identifying novel targets for neuroprotection. Prog Neurobiol. 2014;115:157\u201388.","journal-title":"Prog Neurobiol"},{"key":"1429_CR153","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/964518","volume":"2015","author":"H Prentice","year":"2015","unstructured":"Prentice H, Modi JP, Wu J-Y. Mechanisms of neuronal protection against excitotoxicity, endoplasmic reticulum stress, and mitochondrial dysfunction in stroke and neurodegenerative diseases. Oxid Med Cell Longev. 2015;2015:1\u20137.","journal-title":"Oxid Med Cell Longev"},{"key":"1429_CR154","first-page":"1","volume":"13","author":"Y Sun","year":"2019","unstructured":"Sun Y, Feng X, Ding Y, Li M, Yao J, Wang L, et al. Phased treatment strategies for cerebral ischemia based on glutamate receptors. Front Cell Neurosci. 2019;13:1\u20139.","journal-title":"Front Cell Neurosci"},{"key":"1429_CR155","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41583-021-00488-y","volume":"22","author":"SG Daniele","year":"2021","unstructured":"Daniele SG, Trummer G, Hossmann KA, Vrselja Z, Benk C, Gobeske KT, et al. Brain vulnerability and viability after ischaemia. Nat Rev Neurosci. 2021;22:553\u201372.","journal-title":"Nat Rev Neurosci"},{"key":"1429_CR156","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13041-017-0343-6","volume":"11","author":"QJ Wu","year":"2018","unstructured":"Wu QJ, Tymianski M. Targeting NMDA receptors in stroke: new hope in neuroprotection Tim Bliss. Mol Brain. 2018;11:1\u201314.","journal-title":"Mol Brain"},{"key":"1429_CR157","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ebiom.2018.12.027","volume":"39","author":"M Domercq","year":"2019","unstructured":"Domercq M, Matute C. Excitotoxicity therapy for stroke patients still alive. EBioMedicine. 2019;39:3\u20134.","journal-title":"EBioMedicine"},{"key":"1429_CR158","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.1007\/s12035-020-01984-5","volume":"57","author":"EE Akkuratov","year":"2020","unstructured":"Akkuratov EE, Westin L, Vazquez-Juarez E, de Marothy M, Melnikova AK, Blom H, et al. Ouabain modulates the functional interaction between Na, K-ATPase and NMDA receptor. Mol Neurobiol. 2020;57:4018\u201330.","journal-title":"Mol Neurobiol"},{"key":"1429_CR159","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1016\/j.jagp.2013.09.005","volume":"21","author":"JR Maldonado","year":"2013","unstructured":"Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21:1190\u2013222.","journal-title":"Am J Geriatr Psychiatry"},{"key":"1429_CR160","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1089\/neu.2018.5844","volume":"36","author":"J Bouley","year":"2019","unstructured":"Bouley J, Chung DY, Ayata C, Brown RH, Henninger N. Cortical spreading depression denotes concussion injury. J Neurotrauma. 2019;36:1008\u201317.","journal-title":"J Neurotrauma"},{"key":"1429_CR161","unstructured":"Zhou N. Cellular mechanisms underlying cortical spreading depression. PhD thesis. 2010."},{"key":"1429_CR162","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1093\/brain\/awq284","volume":"133","author":"C Madry","year":"2010","unstructured":"Madry C, Hagler\u00f8d C, Attwell D. The role of pannexin hemichannels in the anoxic depolarization of hippocampal pyramidal cells. Brain. 2010;133:3755\u201363.","journal-title":"Brain"},{"key":"1429_CR163","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/cercor\/11.3.249","volume":"11","author":"CR Jarvis","year":"2001","unstructured":"Jarvis CR, Anderson TR, Andrew RD. Anoxic depolarization mediates acute damage independent of glutamate in neocortical brain slices. Cereb Cortex. 2001;11:249\u201359.","journal-title":"Cereb Cortex"},{"key":"1429_CR164","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1152\/jn.2000.83.2.735","volume":"83","author":"M M\u00fcller","year":"2000","unstructured":"M\u00fcller M, Somjen GG. Na(+) and K(+) concentrations, extra- and intracellular voltages, and the effect of TTX in hypoxic rat hippocampal slices. J Neurophysiol. 2000;83:735\u201345.","journal-title":"J Neurophysiol"},{"key":"1429_CR165","unstructured":"Gagolewicz P, Tressider K, Andrew RD. Still unidentified: the channel driving spreading depolarization during ischemia. Soc Neurosci Abstr 2016;2016-S-148."}],"container-title":["Neurocritical Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12028-021-01429-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12028-021-01429-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12028-021-01429-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T18:39:21Z","timestamp":1657132761000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12028-021-01429-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,22]]},"references-count":165,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["1429"],"URL":"https:\/\/doi.org\/10.1007\/s12028-021-01429-4","relation":{},"ISSN":["1541-6933","1556-0961"],"issn-type":[{"value":"1541-6933","type":"print"},{"value":"1556-0961","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,22]]},"assertion":[{"value":"19 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflicts of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This article adheres to all ethical guidelines outlined by Neurocritical Care for review articles and aims to provide a balanced discussion of an issue of clinical relevance to the journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval\/Informed Consent"}}]}}