{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T04:50:20Z","timestamp":1774414220701,"version":"3.50.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T00:00:00Z","timestamp":1501200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T00:00:00Z","timestamp":1501200000000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spreading depolarization (SD) is a slow propagating wave of strong depolarization of neural cells, implicated in several neuropathological conditions. The breakdown of brain homeostasis promotes significant hemodynamic and metabolic alterations, which impacts on neuronal function. In this work we aimed to develop an innovative multimodal approach, encompassing metabolic, electric and hemodynamic measurements, tailored but not limited to study SD. This was based on a novel dual-biosensor based on microelectrode arrays designed to simultaneously monitor lactate and glucose fluctuations and ongoing neuronal activity with high spatial and temporal resolution. <jats:italic>In vitro<\/jats:italic> evaluation of dual lactate-glucose microbiosensor revealed an extended linear range, high sensitivity and selectivity, fast response time and low oxygen-, temperature- and pH- dependencies. In anesthetized rats, we measured with the same array a significant drop in glucose concentration matched to a rise in lactate and concurrently with pronounced changes in the spectral profile of LFP-related currents during episodes of mechanically-evoked SD. This occurred along with the stereotypical hemodynamic response of the SD wave. Overall, this multimodal approach successfully demonstrates the capability to monitor metabolic alterations and ongoing electrical activity, thus contributing to a better understanding of the metabolic changes occurring in the brain following SD.<\/jats:p>","DOI":"10.1038\/s41598-017-07119-6","type":"journal-article","created":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T09:54:43Z","timestamp":1500890083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Neurometabolic and electrophysiological changes during cortical spreading depolarization: multimodal approach based on a lactate-glucose dual microbiosensor arrays"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0514-0198","authenticated-orcid":false,"given":"C\u00e1tia F.","family":"Louren\u00e7o","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-4241","authenticated-orcid":false,"given":"Ana","family":"Ledo","sequence":"additional","affiliation":[]},{"given":"Greg A.","family":"Gerhardt","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Laranjinha","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-6324","authenticated-orcid":false,"given":"Rui M.","family":"Barbosa","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2017,7,28]]},"reference":[{"key":"7119_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/jcbfm.2010.191","volume":"31","author":"M Lauritzen","year":"2011","unstructured":"Lauritzen, M. et al. 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 \n                           31, 17\u201335, doi:10.1038\/jcbfm.2010.191 (2011).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jocn.2015.08.004","volume":"24","author":"DR Kramer","year":"2016","unstructured":"Kramer, D. R., Fujii, T., Ohiorhenuan, I. & Liu, C. Y. Cortical spreading depolarization: Pathophysiology, implications, and future directions. J Clin Neurosci \n                           24, 22\u201327, doi:10.1016\/j.jocn.2015.08.004 (2016).","journal-title":"J Clin Neurosci"},{"key":"7119_CR3","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/nm.2333","volume":"17","author":"JP Dreier","year":"2011","unstructured":"Dreier, J. P. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med \n                           17, 439\u2013447, doi:10.1038\/nm.2333 (2011).","journal-title":"Nat Med"},{"key":"7119_CR4","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1152\/physrev.00027.2014","volume":"95","author":"C Ayata","year":"2015","unstructured":"Ayata, C. & Lauritzen, M. S. Depression, Spreading Depolarizations, and the Cerebral Vasculature. Physiol Rev \n                           95, 953\u2013993, doi:10.1152\/physrev.00027.2014 (2015).","journal-title":"Physiol Rev"},{"key":"7119_CR5","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16657571","author":"B Balanca","year":"2016","unstructured":"Balanca, B. et al. Altered hypermetabolic response to cortical spreading depolarizations after traumatic brain injury in rats. J Cereb Blood Flow Metab. doi:10.1177\/0271678X16657571 (2016).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR6","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X15612779","author":"D Feuerstein","year":"2015","unstructured":"Feuerstein, D. et al. Regulation of cerebral metabolism during cortical spreading depression. J Cereb Blood Flow Metab. doi:10.1177\/0271678X15612779 (2015).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR7","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/jcbfm.2008.108","volume":"29","author":"P Hashemi","year":"2009","unstructured":"Hashemi, P. et al. Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperaemia: evidence for risk of an adverse effect of Leao\u2019s spreading depression. J Cereb Blood Flow Metab \n                           29, 166\u2013175, doi:10.1038\/jcbfm.2008.108 (2009).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR8","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1021\/cn400047x","volume":"4","author":"ML Rogers","year":"2013","unstructured":"Rogers, M. L. et al. Continuous online microdialysis using microfluidic sensors: dynamic neurometabolic changes during spreading depolarization. ACS Chem Neurosci \n                           4, 799\u2013807, doi:10.1021\/cn400047x (2013).","journal-title":"ACS Chem Neurosci"},{"key":"7119_CR9","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/0304-3940(92)90141-S","volume":"135","author":"D Scheller","year":"1992","unstructured":"Scheller, D., Kolb, J. & Tegtmeier, F. Lactate and pH change in close correlation in the extracellular space of the rat brain during cortical spreading depression. Neurosci Lett \n                           135, 83\u201386 (1992).","journal-title":"Neurosci Lett"},{"key":"7119_CR10","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1097\/01.WCB.0000076701.45782.EF","volume":"23","author":"PM Vespa","year":"2003","unstructured":"Vespa, P. M. et al. Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. J Cereb Blood Flow Metab \n                           23, 865\u2013877, doi:10.1097\/01.WCB.0000076701.45782.EF (2003).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR11","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1093\/brain\/awq353","volume":"134","author":"I Timofeev","year":"2011","unstructured":"Timofeev, I. et al. Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain: a journal of neurology \n                           134, 484\u2013494, doi:10.1093\/brain\/awq353 (2011).","journal-title":"Brain: a journal of neurology"},{"key":"7119_CR12","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16654496","author":"JP Dreier","year":"2016","unstructured":"Dreier, J. P. 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. doi:10.1177\/0271678X16654496 (2016).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR13","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/sj.jcbfm.9600051","volume":"25","author":"M Parkin","year":"2005","unstructured":"Parkin, M. et al. Dynamic changes in brain glucose and lactate in pericontusional areas of the human cerebral cortex, monitored with rapid sampling on-line microdialysis: relationship with depolarisation-like events. J Cereb Blood Flow Metab \n                           25, 402\u2013413, doi:10.1038\/sj.jcbfm.9600051 (2005).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR14","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/S0165-9936(03)00912-9","volume":"22","author":"MC Parkin","year":"2003","unstructured":"Parkin, M. C., Hopwood, S. E. & Boutelle, M. G. Resolving dynamic changes in brain metabolism using biosensors and on-line microdialysis. Trends in Analytical Chemistry \n                           22, 487\u2013497 (2003).","journal-title":"Trends in Analytical Chemistry"},{"key":"7119_CR15","doi-asserted-by":"publisher","first-page":"4503","DOI":"10.1007\/s00216-016-9420-4","volume":"408","author":"A Weltin","year":"2016","unstructured":"Weltin, A., Kieninger, J. & Urban, G. A. Microfabricated, amperometric, enzyme-based biosensors for in vivo applications. Anal Bioanal Chem \n                           408, 4503\u20134521, doi:10.1007\/s00216-016-9420-4 (2016).","journal-title":"Anal Bioanal Chem"},{"key":"7119_CR16","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1016\/j.bios.2007.12.013","volume":"23","author":"JJ Burmeister","year":"2008","unstructured":"Burmeister, J. J. et al. Ceramic-based multisite microelectrode arrays for simultaneous measures of choline and acetylcholine in CNS. Biosens Bioelectron \n                           23, 1382\u20131389, doi:10.1016\/j.bios.2007.12.013 (2008).","journal-title":"Biosens Bioelectron"},{"key":"7119_CR17","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.bios.2015.05.004","volume":"72","author":"N Vasylieva","year":"2015","unstructured":"Vasylieva, N., Marinesco, S., Barbier, D. & Sabac, A. Silicon\/SU8 multi-electrode micro-needle for in vivo neurochemical monitoring. Biosens Bioelectron \n                           72, 148\u2013155, doi:10.1016\/j.bios.2015.05.004 (2015).","journal-title":"Biosens Bioelectron"},{"key":"7119_CR18","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1021\/acs.analchem.6b03772","volume":"89","author":"A Ledo","year":"2017","unstructured":"Ledo, A. et al. Ceramic-Based Multisite Platinum Microelectrode Arrays: Morphological Characteristics and Electrochemical Performance for Extracellular Oxygen Measurements in Brain Tissue. Analytical chemistry \n                           89, 1674\u20131683, doi:10.1021\/acs.analchem.6b03772 (2017).","journal-title":"Analytical chemistry"},{"key":"7119_CR19","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.jneumeth.2009.01.023","volume":"179","author":"H Zhang","year":"2009","unstructured":"Zhang, H., Lin, S. C. & Nicolelis, M. A. Acquiring local field potential information from amperometric neurochemical recordings. J Neurosci Methods \n                           179, 191\u2013200, doi:10.1016\/j.jneumeth.2009.01.023 (2009).","journal-title":"J Neurosci Methods"},{"key":"7119_CR20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jneumeth.2015.07.009","volume":"255","author":"AA Disney","year":"2015","unstructured":"Disney, A. A., McKinney, C., Grissom, L., Lu, X. & Reynolds, J. H. A multi-site array for combined local electrochemistry and electrophysiology in the non-human primate brain. J Neurosci Methods \n                           255, 29\u201337, doi:10.1016\/j.jneumeth.2015.07.009 (2015).","journal-title":"J Neurosci Methods"},{"key":"7119_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneumeth.2012.01.013","volume":"206","author":"A Viggiano","year":"2012","unstructured":"Viggiano, A., Marinesco, S., Pain, F., Meiller, A. & Gurden, H. Reconstruction of field excitatory post-synaptic potentials in the dentate gyrus from amperometric biosensor signals. J Neurosci Methods \n                           206, 1\u20136, doi:10.1016\/j.jneumeth.2012.01.013 (2012).","journal-title":"J Neurosci Methods"},{"key":"7119_CR22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fnhum.2015.00011","volume":"9","author":"PE Rapp","year":"2015","unstructured":"Rapp, P. E. et al. Traumatic brain injury detection using electrophysiological methods. Front Hum Neurosci \n                           9, 11, doi:10.3389\/fnhum.2015.00011 (2015).","journal-title":"Front Hum Neurosci"},{"key":"7119_CR23","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1016\/j.clinph.2016.04.026","volume":"127","author":"DN Hertle","year":"2016","unstructured":"Hertle, D. N. et al. Changes in electrocorticographic beta frequency components precede spreading depolarization in patients with acute brain injury. Clin Neurophysiol \n                           127, 2661\u20132667, doi:10.1016\/j.clinph.2016.04.026 (2016).","journal-title":"Clin Neurophysiol"},{"key":"7119_CR24","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1002\/ana.24256","volume":"76","author":"JA Hartings","year":"2014","unstructured":"Hartings, J. A. et al. Spreading depression in continuous electroencephalography of brain trauma. Ann Neurol \n                           76, 681\u2013694, doi:10.1002\/ana.24256 (2014).","journal-title":"Ann Neurol"},{"key":"7119_CR25","doi-asserted-by":"publisher","first-page":"2928","DOI":"10.1021\/ac971182r","volume":"70","author":"LM Murphy","year":"1998","unstructured":"Murphy, L. M. Reduction of Interference Response at a Hydrogen Peroxide Detecting Electrode Using Electropolymerized Films of Substituted Naphthalenes. Anal Chem \n                           70, 2928\u20132935, doi:10.1021\/ac971182r (1998).","journal-title":"Anal Chem"},{"key":"7119_CR26","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/0006-8993(84)90710-8","volume":"299","author":"JA Stamford","year":"1984","unstructured":"Stamford, J. A., Kruk, Z. L. & Millar, J. Regional differences in extracellular ascorbic acid levels in the rat brain determined by high speed cyclic voltammetry. Brain research \n                           299, 289\u2013295 (1984).","journal-title":"Brain research"},{"key":"7119_CR27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0165-0270(96)00094-5","volume":"70","author":"M Miele","year":"1996","unstructured":"Miele, M. & Fillenz, M. In vivo determination of extracellular brain ascorbate. J Neurosci Methods \n                           70, 15\u201319 (1996).","journal-title":"J Neurosci Methods"},{"key":"7119_CR28","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1002\/elan.201300053","volume":"25","author":"NR Ferreira","year":"2013","unstructured":"Ferreira, N. R., Louren\u00e7o, C. F., Barbosa, R. M. & Laranjinha, J. Real time in vivo measurement of ascorbate in the brain using carbon nanotube-modified microelectrodes. Electroanalysis \n                           25, 1757\u20131763 (2013).","journal-title":"Electroanalysis"},{"key":"7119_CR29","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.snb.2016.06.083","volume":"237","author":"CF Louren\u00e7o","year":"2016","unstructured":"Louren\u00e7o, C. F., Ledo, A., Laranjinha, J., Gerhardt, G. A. & Barbosa, R. M. Microelectrode array biosensor for high-resolution measurements of extracellular glucose in the brain. Sensors and Actuators B: Chemical \n                           237, 298\u2013307, doi:10.1016\/j.snb.2016.06.083 (2016).","journal-title":"Sensors and Actuators B: Chemical"},{"key":"7119_CR30","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.1109\/JSEN.2014.2323220","volume":"14","author":"A Weltin","year":"2014","unstructured":"Weltin, A., Enderle, B., Kieninger, J. & Urban, G. A. Multiparametric, Flexible Microsensor Platform for Metabolic Monitoring In Vivo. Ieee Sens J \n                           14, 3345\u20133351, doi:10.1109\/Jsen.2014.2323220 (2014).","journal-title":"Ieee Sens J"},{"key":"7119_CR31","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1016\/j.bios.2004.07.003","volume":"20","author":"JJ Burmeister","year":"2005","unstructured":"Burmeister, J. J., Palmer, M. & Gerhardt, G. A. L-lactate measures in brain tissue with ceramic-based multisite microelectrodes. Biosens Bioelectron \n                           20, 1772\u20131779, doi:10.1016\/j.bios.2004.07.003 (2005).","journal-title":"Biosens Bioelectron"},{"key":"7119_CR32","doi-asserted-by":"publisher","first-page":"10282","DOI":"10.1021\/ac402071w","volume":"85","author":"G Rocchitta","year":"2013","unstructured":"Rocchitta, G. et al. Simultaneous telemetric monitoring of brain glucose and lactate and motion in freely moving rats. Analytical chemistry \n                           85, 10282\u201310288, doi:10.1021\/ac402071w (2013).","journal-title":"Analytical chemistry"},{"key":"7119_CR33","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.electacta.2013.01.080","volume":"93","author":"I Taurino","year":"2013","unstructured":"Taurino, I. et al. Comparative study of three lactate oxidases from Aerococcus viridans for biosensing applications. Electrochimica Acta \n                           93, 72\u201379, doi:10.1016\/j.electacta.2013.01.080 (2013).","journal-title":"Electrochimica Acta"},{"key":"7119_CR34","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1038\/jcbfm.2009.73","volume":"29","author":"H Piilgaard","year":"2009","unstructured":"Piilgaard, H. & Lauritzen, M. Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex. J Cereb Blood Flow Metab \n                           29, 1517\u20131527, doi:10.1038\/jcbfm.2009.73 (2009).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR35","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1161\/01.STR.18.3.616","volume":"18","author":"PK Nair","year":"1987","unstructured":"Nair, P. K., Buerk, D. G. & Halsey, J. H. Jr. Comparisons of oxygen metabolism and tissue PO2 in cortex and hippocampus of gerbil brain. Stroke \n                           18, 616\u2013622 (1987).","journal-title":"Stroke"},{"key":"7119_CR36","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/BF00374792","volume":"426","author":"R Murr","year":"1994","unstructured":"Murr, R., Berger, S., Schurer, L., Peter, K. & Baethmann, A. A novel, remote-controlled suspension device for brain tissue PO2 measurements with multiwire surface electrodes. Pflugers Arch \n                           426, 348\u2013350 (1994).","journal-title":"Pflugers Arch"},{"key":"7119_CR37","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/BF00999769","volume":"4","author":"JC LaManna","year":"1989","unstructured":"LaManna, J. C., McCracken, K. A., Patil, M. & Prohaska, O. J. Stimulus-activated changes in brain tissue temperature in the anesthetized rat. Metab Brain Dis \n                           4, 225\u2013237 (1989).","journal-title":"Metab Brain Dis"},{"key":"7119_CR38","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.1093\/brain\/awu241","volume":"137","author":"JM Hinzman","year":"2014","unstructured":"Hinzman, J. M. et al. Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma. Brain: a journal of neurology \n                           137, 2960\u20132972, doi:10.1093\/brain\/awu241 (2014).","journal-title":"Brain: a journal of neurology"},{"key":"7119_CR39","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1161\/STROKEAHA.114.008077","volume":"46","author":"L Ostergaard","year":"2015","unstructured":"Ostergaard, L. et al. Neurovascular coupling during cortical spreading depolarization and -depression. Stroke \n                           46, 1392\u20131401, doi:10.1161\/STROKEAHA.114.008077 (2015).","journal-title":"Stroke"},{"key":"7119_CR40","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1212\/WNL.0b013e3182886932","volume":"80","author":"J Woitzik","year":"2013","unstructured":"Woitzik, J. et al. Propagation of cortical spreading depolarization in the human cortex after malignant stroke. Neurology \n                           80, 1095\u20131102, doi:10.1212\/WNL.0b013e3182886932 (2013).","journal-title":"Neurology"},{"key":"7119_CR41","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1038\/jcbfm.2014.153","volume":"34","author":"GA Dienel","year":"2014","unstructured":"Dienel, G. A. Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations. J Cereb Blood Flow Metab \n                           34, 1736\u20131748, doi:10.1038\/jcbfm.2014.153 (2014).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR42","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1046\/j.1528-1157.2002.01602.x","volume":"43","author":"EM Cornford","year":"2002","unstructured":"Cornford, E. M. et al. Regional analyses of CNS microdialysate glucose and lactate in seizure patients. Epilepsia \n                           43, 1360\u20131371 (2002).","journal-title":"Epilepsia"},{"key":"7119_CR43","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1097\/00003246-199909000-00041","volume":"27","author":"JC Goodman","year":"1999","unstructured":"Goodman, J. C., Valadka, A. B., Gopinath, S. P., Uzura, M. & Robertson, C. S. Extracellular lactate and glucose alterations in the brain after head injury measured by microdialysis. Crit Care Med \n                           27, 1965\u20131973 (1999).","journal-title":"Crit Care Med"},{"key":"7119_CR44","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1155\/1995\/139835","volume":"8","author":"AO Ogunyemi","year":"1995","unstructured":"Ogunyemi, A. O. Migraine with prolonged aura: correlation of clinical and EEG features. Behav Neurol \n                           8, 109\u2013114, doi:10.3233\/BEN-1995-8206 (1995).","journal-title":"Behav Neurol"},{"issue":"(Pt 1)","key":"7119_CR45","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/brain\/117.1.199","volume":"117","author":"M Lauritzen","year":"1994","unstructured":"Lauritzen, M. Pathophysiology of the migraine aura. The spreading depression theory. Brain: a journal of neurology \n                           117((Pt 1)), 199\u2013210 (1994).","journal-title":"Brain: a journal of neurology"},{"key":"7119_CR46","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s11055-006-0067-z","volume":"36","author":"VI Koroleva","year":"2006","unstructured":"Koroleva, V. I., Davydov, V. I. & Roshchina, G. Y. Suppression of EEG gamma activity\u2013an informative measure of spreading depression waves in the neocortex of the conscious rabbit. Neurosci Behav Physiol \n                           36, 625\u2013630, doi:10.1007\/s11055-006-0067-z (2006).","journal-title":"Neurosci Behav Physiol"},{"key":"7119_CR47","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1093\/brain\/awp338","volume":"133","author":"JC Chang","year":"2010","unstructured":"Chang, J. C. et al. Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression. Brain: a journal of neurology \n                           133, 996\u20131012, doi:10.1093\/brain\/awp338 (2010).","journal-title":"Brain: a journal of neurology"},{"key":"7119_CR48","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/jcbfm.1989.11","volume":"9","author":"S Tomida","year":"1989","unstructured":"Tomida, S., Wagner, H. G., Klatzo, I. & Nowak, T. S. Jr. Effect of acute electrode placement on regional CBF in the gerbil: a comparison of blood flow measured by hydrogen clearance, [3H]nicotine, and [14C]iodoantipyrine techniques. J Cereb Blood Flow Metab \n                           9, 79\u201386, doi:10.1038\/jcbfm.1989.11 (1989).","journal-title":"J Cereb Blood Flow Metab"},{"key":"7119_CR49","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1007\/s11055-014-9887-4","volume":"44","author":"GY Roshchina","year":"2014","unstructured":"Roshchina, G. Y., Koroleva, V. I. & Davydov, V. I. Effects of the Functional State of the Brain Evoked by Passage of a Spreading Depression Wave on the Properties of Subsequent Wave. Neurosci Behav Physiol \n                           44, 134\u2013140, doi:10.1007\/s11055-014-9887-4 (2014).","journal-title":"Neurosci Behav Physiol"},{"key":"7119_CR50","unstructured":"Paxinos, G. & Watson, C. The Rat Brain in Sterotaxic Coordinates. Academic Press, San Diego (2007)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07119-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07119-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07119-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T07:37:53Z","timestamp":1671781073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07119-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,28]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["7119"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-07119-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,28]]},"assertion":[{"value":"23 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"G.A.G. is the sole proprietor of Quanteon, LLC which manufactures the Fast16 recording system used for control of the MEA technology.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6764"}}