{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:10:34Z","timestamp":1779941434872,"version":"3.53.1"},"reference-count":77,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT 148896"],"award-info":[{"award-number":["PJT 148896"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-17-1-0684"],"award-info":[{"award-number":["W81XWH-17-1-0684"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG DR 323\/5-1"],"award-info":[{"award-number":["DFG DR 323\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG DR 323\/10-1"],"award-info":[{"award-number":["DFG DR 323\/10-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7 no 602150 CENTER-TBI"],"award-info":[{"award-number":["FP7 no 602150 CENTER-TBI"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004489","name":"Mitacs","doi-asserted-by":"publisher","award":["IT13603"],"award-info":[{"award-number":["IT13603"]}],"id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) is the leading cause of death in young individuals, and is a major health concern that often leads to long-lasting complications. However, the electrophysiological events that occur immediately after traumatic brain injury, and may underlie impact outcomes, have not been fully elucidated. To investigate the electrophysiological events that immediately follow traumatic brain injury, a weight-drop model of traumatic brain injury was used in rats pre-implanted with epidural and intracerebral electrodes. Electrophysiological (near-direct current) recordings and simultaneous alternating current recordings of brain activity were started within seconds following impact. Cortical spreading depolarization (SD) and SD-induced spreading depression occurred in approximately 50% of mild and severe impacts. SD was recorded within three minutes after injury in either one or both brain hemispheres. Electrographic seizures were rare. While both TBI- and electrically induced SDs resulted in elevated oxidative stress, TBI-exposed brains showed a reduced antioxidant defense. In severe TBI, brainstem SD could be recorded in addition to cortical SD, but this did not lead to the death of the animals. Severe impact, however, led to immediate death in 24% of animals, and was electrocorticographically characterized by non-spreading depression (NSD) of activity followed by terminal SD in both cortex and brainstem.<\/jats:p>","DOI":"10.3390\/ijms222111642","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T23:51:36Z","timestamp":1635465096000},"page":"11642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Brainstem and Cortical Spreading Depolarization in a Closed Head Injury Rat Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4398-1609","authenticated-orcid":false,"given":"Refat","family":"Aboghazleh","sequence":"first","affiliation":[{"name":"Department of Medical Neuroscience, Faculty of Medicine and Brain Repair Centre, Dalhousie University, Halifax, NS B3H 4H7, Canada"},{"name":"Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt 19110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Medical Neuroscience, Faculty of Medicine and Brain Repair Centre, Dalhousie University, Halifax, NS B3H 4H7, Canada"},{"name":"Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2325-6423","authenticated-orcid":false,"given":"Lynn T.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Kaufer","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens P.","family":"Dreier","sequence":"additional","affiliation":[{"name":"Center for Stroke Research Berlin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Department of Experimental Neurology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Department of Neurology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Bernstein Center for Computational Neuroscience Berlin, 10115 Berlin, Germany"},{"name":"Einstein Center for Neurosciences Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alon","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Medical Neuroscience, Faculty of Medicine and Brain Repair Centre, Dalhousie University, Halifax, NS B3H 4H7, Canada"},{"name":"Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0105-8098","authenticated-orcid":false,"given":"Gerben","family":"van Hameren","sequence":"additional","affiliation":[{"name":"Department of Medical Neuroscience, Faculty of Medicine and Brain Repair Centre, Dalhousie University, Halifax, NS B3H 4H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S354","DOI":"10.1016\/j.pmrj.2011.07.017","article-title":"Epidemiology of Concussion and Mild Traumatic Brain Injury","volume":"3","author":"Laker","year":"2011","journal-title":"PM&R"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mcn.2015.03.001","article-title":"Epidemiology of Mild Traumatic Brain Injury and Neurodegenerative Disease","volume":"66","author":"Gardner","year":"2015","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1474-4422(17)30371-X","article-title":"Traumatic Brain Injury: Integrated Approaches to Improve Prevention, Clinical Care, and Research","volume":"16","author":"Maas","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1136\/practneurol-2015-001087","article-title":"Concussion Is Confusing Us All","volume":"15","author":"Sharp","year":"2015","journal-title":"Pract. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0301-0082(02)00018-7","article-title":"The Neurophysiology of Concussion","volume":"67","author":"Shaw","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/S1474-4422(08)70164-9","article-title":"Moderate and Severe Traumatic Brain Injury in Adults","volume":"7","author":"Maas","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/02699052.2018.1429018","article-title":"Diffuse Axonal Injury after Traumatic Brain Injury Is a Prognostic Factor for Functional Outcome: A Systematic Review and Meta-Analysis","volume":"32","author":"Schoonman","year":"2018","journal-title":"Brain Inj."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/S0140-6736(05)67626-X","article-title":"Trends in Head Injury Outcome from 1989 to 2003 and the Effect of Neurosurgical Care: An Observational Study","volume":"366","author":"Patel","year":"2005","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1136\/jnnp.51.5.722","article-title":"Anxiety and Depression after Mild Head Injury: A Case Control Study","volume":"51","author":"Schoenhuber","year":"1988","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1528-1167.2012.03612.x","article-title":"Traumatic Brain Injury: Risks of Epilepsy and Implications for Medicolegal Assessment","volume":"53","author":"Christensen","year":"2012","journal-title":"Epilepsia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrneurol.2010.74","article-title":"Blood-Brain Barrier Breakdown as a Therapeutic Target in Traumatic Brain Injury","volume":"6","author":"Shlosberg","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11916-015-0522-z","article-title":"Concussion in Chronic Traumatic Encephalopathy","volume":"19","author":"Stein","year":"2015","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/mds.25458","article-title":"Head Injury and Risk of Parkinson Disease: A Systematic Review and Meta-Analysis","volume":"28","author":"Jafari","year":"2013","journal-title":"Mov. Disord. Off. J. Mov. Disord. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.1093\/ije\/20.Supplement_2.S28","article-title":"Head Trauma as a Risk Factor for Alzheimer\u2019s Disease: A Collaborative Re-Analysis of Case-Control Studies. EURODEM Risk Factors Research Group","volume":"20","author":"Mortimer","year":"1991","journal-title":"Int. J. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.emc.2010.03.003","article-title":"Traumatic Alterations in Consciousness: Traumatic Brain Injury","volume":"28","author":"Blyth","year":"2010","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_16","first-page":"527","article-title":"Post-Traumatic Epilepsy: An Overview","volume":"7","author":"Verellen","year":"2010","journal-title":"Ther. Lond. Engl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/ana.21721","article-title":"Intracortical Electroencephalography in Acute Brain Injury","volume":"66","author":"Waziri","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1038\/jcbfm.2008.30","article-title":"Role of Cortical Spreading Depressions for Secondary Brain Damage after Traumatic Brain Injury in Mice","volume":"28","author":"Trabold","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1001\/jamaneurol.2019.4476","article-title":"Prognostic Value of Spreading Depolarizations in Patients With Severe Traumatic Brain Injury","volume":"77","author":"Hartings","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1093\/brain\/awh716","article-title":"Cortical Spreading Depression and Peri-Infarct Depolarization in Acutely Injured Human Cerebral Cortex","volume":"129","author":"Fabricius","year":"2006","journal-title":"Brain J. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1177\/1073858412453340","article-title":"Is Spreading Depolarization Characterized by an Abrupt, Massive Release of Gibbs Free Energy from the Human Brain Cortex?","volume":"19","author":"Dreier","year":"2012","journal-title":"Neuroscientist"},{"key":"ref_22","first-page":"189","article-title":"Spreading Depolarization Is Not an Epiphenomenon but the Principal Mechanism of the Cytotoxic Edema in Various Gray Matter Structures of the Brain during Stroke","volume":"134","author":"Dreier","year":"2018","journal-title":"Cereb. Ischemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1093\/cercor\/bhaa134","article-title":"Rapid Neuronal Ultrastructure Disruption and Recovery during Spreading Depolarization-Induced Cytotoxic Edema","volume":"30","author":"Kirov","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1152\/jn.00237.2002","article-title":"Conditions for the Triggering of Spreading Depression Studied with Computer Simulations","volume":"88","author":"Kager","year":"2002","journal-title":"J. Neurophysiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1177\/0271678X16654496","article-title":"Recording, Analysis, and Interpretation of Spreading Depolarizations in Neurointensive Care: Review and Recommendations of the COSBID Research Group","volume":"37","author":"Dreier","year":"2017","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/ana.25147","article-title":"Terminal Spreading Depolarization and Electrical Silence in Death of Human Cerebral Cortex","volume":"83","author":"Dreier","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nm.2333","article-title":"The Role of Spreading Depression, Spreading Depolarization and Spreading Ischemia in Neurological Disease","volume":"17","author":"Dreier","year":"2011","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1089\/neu.2009.0961","article-title":"Co-Operative Study of Brain Injury Depolarizations Spreading Depolarizations and Late Secondary Insults after Traumatic Brain Injury","volume":"26","author":"Hartings","year":"2009","journal-title":"J. Neurotrauma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/j.clinph.2008.05.025","article-title":"Association of Seizures with Cortical Spreading Depression and Peri-Infarct Depolarisations in the Acutely Injured Human Brain","volume":"119","author":"Fabricius","year":"2008","journal-title":"Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/brain\/awr303","article-title":"Spreading Convulsions, Spreading Depolarization and Epileptogenesis in Human Cerebral Cortex","volume":"135","author":"Dreier","year":"2012","journal-title":"Brain J. Neurol."},{"key":"ref_31","unstructured":"Varelas, P.N., and Claassen, J. (2017). Spreading Depolarizations and Seizures in Clinical Subdural Electrocorticographic Recordings. Seizures in Critical Care: A Guide to Diagnosis and Therapeutics, Springer International Publishing."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1212\/WNL.0b013e3182886932","article-title":"Propagation of Cortical Spreading Depolarization in the Human Cortex after Malignant Stroke","volume":"80","author":"Woitzik","year":"2013","journal-title":"Neurology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/ana.21390","article-title":"Spreading Depolarizations Occur in Human Ischemic Stroke with High Incidence","volume":"63","author":"Dohmen","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/S1474-4422(11)70243-5","article-title":"Spreading Depolarisations and Outcome after Traumatic Brain Injury: A Prospective Observational Study","volume":"10","author":"Hartings","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1093\/brain\/awu241","article-title":"Inverse Neurovascular Coupling to Cortical Spreading Depolarizations in Severe Brain Trauma","volume":"137","author":"Hinzman","year":"2014","journal-title":"Brain J. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1093\/brain\/awp102","article-title":"Cortical Spreading Ischaemia Is a Novel Process Involved in Ischaemic Damage in Patients with Aneurysmal Subarachnoid Haemorrhage","volume":"132","author":"Dreier","year":"2009","journal-title":"Brain J. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1528-1167.2012.03699.x","article-title":"Impaired Neurovascular Coupling to Ictal Epileptic Activity and Spreading Depolarization in a Patient with Subarachnoid Hemorrhage: Possible Link to Blood-Brain Barrier Dysfunction","volume":"53","author":"Winkler","year":"2012","journal-title":"Epilepsia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1152\/physrev.2001.81.3.1065","article-title":"Mechanisms of Spreading Depression and Hypoxic Spreading Depression-like Depolarization","volume":"81","author":"Somjen","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/jcbfm.2010.40","article-title":"Experimental and Preliminary Clinical Evidence of an Ischemic Zone with Prolonged Negative DC Shifts Surrounded by a Normally Perfused Tissue Belt with Persistent Electrocorticographic Depression","volume":"30","author":"Milakara","year":"2010","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.expneurol.2010.03.004","article-title":"The Relationship between Sudden Severe Hypoxia and Ischemia-Associated Spreading Depolarization in Adult Rat Brainstem In Vivo","volume":"224","author":"Richter","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"282ra46","DOI":"10.1126\/scitranslmed.aaa4050","article-title":"Spreading Depolarization in the Brainstem Mediates Sudden Cardiorespiratory Arrest in Mouse SUDEP Models","volume":"7","author":"Aiba","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1089\/neu.2018.5844","article-title":"Cortical Spreading Depression Denotes Concussion Injury","volume":"36","author":"Bouley","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"ENEURO.0070-19.2019","DOI":"10.1523\/ENEURO.0070-19.2019","article-title":"Spreading Depolarizations Occur in Mild Traumatic Brain Injuries and Are Associated with Postinjury Behavior","volume":"6","author":"Pacheco","year":"2019","journal-title":"eNeuro"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"708","DOI":"10.3171\/jns.1981.55.5.0708","article-title":"Changes in Extracellular Potassium Concentration in Cortex and Brain Stem during the Acute Phase of Experimental Closed Head Injury","volume":"55","author":"Takahashi","year":"1981","journal-title":"J. Neurosurg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1093\/brain\/awl297","article-title":"Delayed Ischaemic Neurological Deficits after Subarachnoid Haemorrhage Are Associated with Clusters of Spreading Depolarizations","volume":"129","author":"Dreier","year":"2006","journal-title":"Brain J. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1177\/0271678X16657571","article-title":"Altered Hypermetabolic Response to Cortical Spreading Depolarizations after Traumatic Brain Injury in Rats","volume":"37","author":"Meiller","year":"2017","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1161\/STROKEAHA.107.500710","article-title":"Nitric Oxide Modulates Spreading Depolarization Threshold in the Human and Rodent Cortex","volume":"39","author":"Petzold","year":"2008","journal-title":"Stroke"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1177\/0271678X19861604","article-title":"Spreading Depolarizations in the Rat Endothelin-1 Model of Focal Cerebellar Ischemia","volume":"40","author":"Major","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"302","DOI":"10.4172\/Neuropsychiatry.1000351","article-title":"Characterization of Intrinsic Optical Signal during Spreading Depolarization","volume":"8","author":"Zheng","year":"2018","journal-title":"Neuropsychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1161\/STROKEAHA.111.621581","article-title":"Chronically Epileptic Human and Rat Neocortex Display a Similar Resistance Against Spreading Depolarization In Vitro","volume":"42","author":"Maslarova","year":"2011","journal-title":"Stroke"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Man\u00e9, M., and M\u00fcller, M. (2012). Temporo-Spectral Imaging of Intrinsic Optical Signals during Hypoxia-Induced Spreading Depression-like Depolarization. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043981"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/jcbfm.1992.32","article-title":"The Effect of Glutamate Receptor Blockade on Anoxic Depolarization and Cortical Spreading Depression","volume":"12","author":"Lauritzen","year":"1992","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1177\/0271678X19833757","article-title":"Na+\/K+-ATPase \u03b1 Isoform Deficiency Results in Distinct Spreading Depolarization Phenotypes","volume":"40","author":"Reiffurth","year":"2019","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2174\/1871527317666180627120501","article-title":"Oxidative Stress: Major Threat in Traumatic Brain Injury","volume":"17","author":"Khatri","year":"2018","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.2174\/0929867321666131217153310","article-title":"Oxidative Stress in Traumatic Brain Injury","volume":"21","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0014-4886(03)00254-1","article-title":"Susceptibility of Hippocampal Neurons to Mechanically Induced Injury","volume":"184","author":"Geddes","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"652721","DOI":"10.3389\/fncel.2021.652721","article-title":"Sustained Hippocampal Synaptic Pathophysiology Following Single and Repeated Closed-Head Concussive Impacts","volume":"15","author":"McDaid","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.expneurol.2013.11.003","article-title":"Isoflurane Suppresses Cortical Spreading Depolarizations Compared to Propofol-Implications for Sedation of Neurocritical Care Patients","volume":"252","author":"Takagaki","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1093\/brain\/awx214","article-title":"Subarachnoid Blood Acutely Induces Spreading Depolarizations and Early Cortical Infarction","volume":"140","author":"Hartings","year":"2017","journal-title":"Brain J. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1093\/brain\/awr048","article-title":"Spreading Depolarizations Have Prolonged Direct Current Shifts and Are Associated with Poor Outcome in Brain Trauma","volume":"134","author":"Hartings","year":"2011","journal-title":"Brain"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/brain\/awy102","article-title":"The Negative Ultraslow Potential, Electrophysiological Correlate of Infarction in the Human Cortex","volume":"141","author":"Lemale","year":"2018","journal-title":"Brain J. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1177\/0271678X16651269","article-title":"Spreading Depolarizations in Patients with Spontaneous Intracerebral Hemorrhage: Association with Perihematomal Edema Progression","volume":"37","author":"Helbok","year":"2017","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.3171\/2020.1.JNS192914","article-title":"Spreading Depolarization May Represent a Novel Mechanism for Delayed Fluctuating Neurological Deficit after Chronic Subdural Hematoma Evacuation","volume":"134","author":"Mohammad","year":"2020","journal-title":"J. Neurosurg."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tweedie, D., Fukui, K., Li, Y., Yu, Q., Barak, S., Tamargo, I.A., Rubovitch, V., Holloway, H.W., Lehrmann, E., and Wood, W.H. (2016). Cognitive Impairments Induced by Concussive Mild Traumatic Brain Injury in Mouse Are Ameliorated by Treatment with Phenserine via Multiple Non-Cholinergic and Cholinergic Mechanisms. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156493"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1097\/TA.0000000000001248","article-title":"A Model of Recurrent Concussion That Leads to Long-Term Motor Deficits, CTE-like Tauopathy and Exacerbation of an ALS Phenotype","volume":"81","author":"Thomsen","year":"2016","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_66","first-page":"2929","article-title":"Recombinant PEP-1-SOD1 Improves Functional Recovery after Neural Stem Cell Transplantation in Rats with Traumatic Brain Injury","volume":"15","author":"Jia","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9633","DOI":"10.1523\/JNEUROSCI.1713-19.2019","article-title":"Apnea Associated with Brainstem Seizures in Cacna1a (S218L) Mice Is Caused by Medullary Spreading Depolarization","volume":"39","author":"Jansen","year":"2019","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/brain\/awy325","article-title":"Brainstem Spreading Depolarization and Cortical Dynamics during Fatal Seizures in Cacna1a S218L Mice","volume":"142","author":"Loonen","year":"2019","journal-title":"Brain J. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mayevsky, A. (2015). Responses of NADH to Physiological and Pathophysiological Conditions. Mitochondrial Function In Vivo Evaluated by NADH Fluorescence, Springer International Publishing.","DOI":"10.1007\/978-3-319-16682-7"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3389\/fnins.2019.00373","article-title":"Correlates of Spreading Depolarization, Spreading Depression, and Negative Ultraslow Potential in Epidural versus Subdural Electrocorticography","volume":"13","author":"Dreier","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1097\/00004647-199708000-00004","article-title":"Reduction of Infarct Volume by Halothane: Effect on Cerebral Blood Flow or Perifocal Spreading Depression-Like Depolarizations","volume":"17","author":"Saito","year":"1997","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuroimage.2009.08.009","article-title":"Dynamic in Vivo Imaging of Cerebral Blood Flow and Blood-Brain Barrier Permeability","volume":"49","author":"Prager","year":"2010","journal-title":"NeuroImage"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1089\/neu.2013.3132","article-title":"Assessment of an Experimental Rodent Model of Pediatric Mild Traumatic Brain Injury","volume":"31","author":"Mychasiuk","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.1523\/JNEUROSCI.3694-15.2016","article-title":"Susceptibility of Primary Sensory Cortex to Spreading Depolarizations","volume":"36","author":"Bogdanov","year":"2016","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/cvr\/cvv279","article-title":"Succinate Dehydrogenase Inhibition with Malonate during Reperfusion Reduces Infarct Size by Preventing Mitochondrial Permeability Transition","volume":"109","author":"Barba","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1042\/cs0840407","article-title":"A Novel Method for Measuring Antioxidant Capacity and Its Application to Monitoring the Antioxidant Status in Premature Neonates","volume":"84","author":"Miller","year":"1993","journal-title":"Clin. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/brain\/awx350","article-title":"Concussion, Microvascular Injury, and Early Tauopathy in Young Athletes after Impact Head Injury and an Impact Concussion Mouse Model","volume":"141","author":"Tagge","year":"2018","journal-title":"Brain J. Neurol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11642\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:21:43Z","timestamp":1760167303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,28]]},"references-count":77,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111642"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111642","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,28]]}}}