arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2020-26-1-27-36arthyper-1848Research ArticleОбзоры и лекцииReviewNR2-антитела как диагностический и прогностический биомаркер при инсультеNR2 antibodies as diagnostic and prognostic stroke biomarkerhttps://orcid.org/0000-0002-0175-3085ТопузоваМ. П.TopuzovaM. P.

Топузова Мария Петровна — кандидат медицинских наук, доцент кафедры неврологии и психиатрии, старший научный сотрудник научно-исследовательской лаборатории (НИЛ) цереброваскулярной патологии научно-исследовательского отдела (НИО) неврологии и нейрореабилитации

ул. Аккуратова, д. 2, Санкт-Петербург, 197341

Mariya P. Topuzova, MD, PhD, Senior Researcher, Associate Professor, Department of Neurology and Psychiatry, Senior Researcher, Research Laboratory of Cerebrovascular Pathology, Research Department of Neurology and Neurorehabilitation

2 Akkuratov street, St Petersburg, 197341

marcun@rambler.ruhttps://orcid.org/0000-0002-4441-1165АлексееваТ. М.AlekseevaT. M.

Алексеева Татьяна Михайловна — доктор медицинских наук, доцент, заведующая кафедрой неврологии и психиатрии, заведующая НИЛ цереброваскулярной патологии НИО неврологии и нейрореабилитации 

Санкт-Петербург

Tat’yana M. Alekseeva, MD, PhD, DSc, Associate Professor, Head, Department of Neurology and Psychiatry, Head, Research Laboratory of Cerebrovascular Pathology, Research Department of Neurology and Neurorehabilitation

St Petersburg

alekseeva_tm@almazovcentre.ruhttps://orcid.org/0000-0003-3637-5405ПанинаЕ. Б.PaninaE. B.

Панина Елена Борисовна — кандидат медицинских наук, доцент кафедры неврологии и психиатрии 

Санкт-Петербург

Elena B. Panina, MD, PhD, Associate Professor, Department of Neurology and Psychiatry

St Petersburg

panina_eb@almazovcentre.ruhttps://orcid.org/0000-0001-8537-3639ВавиловаТ. В.VavilovaT. V.

Вавилова Татьяна Владимировна — доктор медицинских наук, профессор, заведующая кафедрой лабораторной медицины и генетики 

Санкт-Петербург

Tat’yana V. Vavilova, MD, PhD, DSc, Professor, Head, Department of Laboratory Medicine and Genetics

St Petersburg

vavilova_tm@almazovcentre.ruhttps://orcid.org/0000-0003-3553-6537ПоспеловаМ. Л.PospelovaM. L.

Поспелова Мария Львовна — доктор медицинских наук, ведущий научный сотрудник НИЛ цереброваскулярной патологии НИО неврологии и нейрореабилитации, доцент кафедры неврологии и психиатрии Института медицинского образования 

Санкт-Петербург

Maria L. Pospelova, MD, PhD, DSc, Leading Researcher, Laboratory of Cerebrovascular Pathology, Research and Development Department of Neurology and Neurorehabilitation, Associate Professor, Department of Neurology and Psychiatry

St Petersburg

pospelova_tm@almazovcentre.ruhttps://orcid.org/0000-0003-2790-0191ИвановаН. Е.IvanovaN. E.

Иванова Наталья Евгеньевна — доктор медицинских наук, профессор, заведующая научным отделом Российского научно-хирургического института имени профессора А. Л. Поленова филиала ФГБУ «НМИЦ им. В. А. Алмазова» Минздрава России

Санкт-Петербург

Natalia E. Ivanova, MD, PhD, DSc, Professor, Head, Scientific Department, Russian Neurosurgical Institute named after professor A. L. Polenova branch of Almazov National Medical Research Centre

St Petersburg

ivanova_ne@almazovcentre.ruФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени B. A. Алмaзoвa» Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research CentreRussian Federation2020131220192612736Copyright © Топузова М.П., Алексеева Т.М., Панина Е.Б., Вавилова Т.В., Поспелова М.Л., Иванова Н.Е., 20202020Топузова М.П., Алексеева Т.М., Панина Е.Б., Вавилова Т.В., Поспелова М.Л., Иванова Н.Е.Topuzova M.P., Alekseeva T.M., Panina E.B., Vavilova T.V., Pospelova M.L., Ivanova N.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/1848

Учитывая высокий процент инвалидизации и смертности в результате перенесенного инсульта, в настоящее время является перспективным поиск новых возможностей для улучшения ранней диагностики и оптимизации терапевтических подходов. В статье представлен обзор литературы, посвященной изучению NR2-антител к глутаматным N-метил-D-аспартат (NMDA) рецепторам в качестве биомаркера в остром периоде инсульта. Проведенный обзор показал, что данный биомаркер пригоден для определения наличия ишемического процесса в мозге и степени разрушения мозговой ткани, как в первые часы инсульта, так и в динамике. Кроме того, анализ NR2-антител может быть информативен для контроля за течением заболевания в случае увеличения размеров очага, что может способствовать своевременной коррекции лечения и позволит улучшить эффективность проводимой терапии. Важным параметром можно считать прогностический потенциал NR2-антител, что может быть использовано для оптимизации персонифицированного терапевтического подхода. Однако малочисленность исследований NR2-антител в остром периоде инсульта на сегодняшний день требует дальнейшего изучения данного биомаркера.

Given the high percentage of disability and mortality resulting from a stroke, search of new ways to improve early diagnosis and optimize therapeutic approaches is highly relevant. The article reviews the studies of NR2 antibodies to glutamate N-methyl-D-aspartate (NMDA) receptors as a biomarker in acute stroke. The review shows that this biomarker is suitable for determining the presence of ischemic process in the brain and the degree of destruction of brain tissue, both in the first hours of stroke and at follow-up. In addition, the analysis of NR2 antibodies can be informative to predict the worsening, the increase in the locus size, which can contribute to the timely correction of treatment and will improve the effectiveness of the therapy. The prognostic potential of NR2 antibodies can be used for personalized therapeutic approach. However, currently the lack of studies of NR2 antibodies in acute stroke requires further study of this biomarker.

инсультбиомаркеры инсультаNR2-антителаN-метил-D-аспартат (NMDA) рецепторыпрогнозstrokebiomarkers of strokeNR2-antibodiesN-methyl-D-aspartate (NMDA) receptorsprognosisReferencesFeigin VL, Norrving B, George MG, Foltz JL, Roth GA, Mensah GA. Prevention of stroke: a strategic global imperative. Nat Rev Neurol. 2016;12(9):501–512. doi:10.1038/nrneurol.2016.107Feigin VL, Norrving B, George MG, Foltz JL, Roth GA, Mensah GA. Prevention of stroke: a strategic global imperative. Nat Rev Neurol. 2016;12(9):501–512. doi:10.1038/nrneurol.2016.107Castellanos MI, Serena J. Applicability of biomarkers in ischemic stroke. Cerebrovasc Dis. 2007;24(1):7–15. doi.org/10.1159/000107374Castellanos MI, Serena J. Applicability of biomarkers in ischemic stroke. Cerebrovasc Dis. 2007;24(1):7–15. doi.org/10.1159/000107374Strimbu K, Tavel JA. What are biomarkers? Current Opinion in HIV and AIDS. 2010;5(6):463–466. doi:10.1097/coh.0b013e32833ed177Strimbu K, Tavel JA. What are biomarkers? Current Opinion in HIV and AIDS. 2010;5(6):463–466. doi:10.1097/coh.0b013e32833ed177Biomarkers Definitions Working Group. Biomarkers and surrogate end points: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. doi:10.1067/mcp.2001.113989Biomarkers Definitions Working Group. Biomarkers and surrogate end points: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. doi:10.1067/mcp.2001.113989Hill MD, Jackowski G, Bayer N, Lawrence M, Jaeschke R. Biochemical markers in acute ischemic stroke. CMAJ. 2000; 162(8):1139–1140.Hill MD, Jackowski G, Bayer N, Lawrence M, Jaeschke R. Biochemical markers in acute ischemic stroke. CMAJ. 2000; 162(8):1139–1140.Kogure T, Kogure K. Molecular and biochemical events within the brain subjected to cerebral ischemia (targets for therapeutical intervention). Clin Neurosci. 1997;4(4):179–183.Kogure T, Kogure K. Molecular and biochemical events within the brain subjected to cerebral ischemia (targets for therapeutical intervention). Clin Neurosci. 1997;4(4):179–183.Shimada N, Graf R, Rosner G, Wakayama A, George CP, Heiss WD. Ischemic flow threshold for extracellular glutamate increase in cat cortex. J Cereb Blood Flow Metab. 1989;9(5): 603–606.Shimada N, Graf R, Rosner G, Wakayama A, George CP, Heiss WD. Ischemic flow threshold for extracellular glutamate increase in cat cortex. J Cereb Blood Flow Metab. 1989;9(5): 603–606.Jones TH, Morawetz RB, Crowell RM, Marcoux FW, FitzGibbon SJ, DeGirolami U et al. Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg. 1981;54(6):773–782.Jones TH, Morawetz RB, Crowell RM, Marcoux FW, FitzGibbon SJ, DeGirolami U et al. Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg. 1981;54(6):773–782.Coffey ET, Sihra TS, Nicholls DG, Pocock JM. Phosphorylation of synapsin I and MARCKS in nerve terminals is mediated by Ca 2+ entry via an Aga-GI sensitive Ca2+ channel which is coupled to glutamate exocytosis. FEBS Lett. 1994;353:264–268.Coffey ET, Sihra TS, Nicholls DG, Pocock JM. Phosphorylation of synapsin I and MARCKS in nerve terminals is mediated by Ca 2+ entry via an Aga-GI sensitive Ca2+ channel which is coupled to glutamate exocytosis. FEBS Lett. 1994;353:264–268.Mena FV, Baab PJ, Zielke CL, Zielke HR. In vivo glutamine hydrolysis in the formation of extracellular glutamate in the injured rat brain. J Neurosci Res. 2000;60(5):632–641.Mena FV, Baab PJ, Zielke CL, Zielke HR. In vivo glutamine hydrolysis in the formation of extracellular glutamate in the injured rat brain. J Neurosci Res. 2000;60(5):632–641.Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000;130(4S):1007S-1015S. doi:10.1093/jn/130.4.1007SMeldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000;130(4S):1007S-1015S. doi:10.1093/jn/130.4.1007SPlatt SR. The role of glutamate in central nervous system health and disease — a review. Vet J. 2007;173(2):278–286. doi:10.1016/j.tvjl.2005.11.007Platt SR. The role of glutamate in central nervous system health and disease — a review. Vet J. 2007;173(2):278–286. doi:10.1016/j.tvjl.2005.11.007Okubo Y, Sekiya H, Namiki S, Sakamoto H, Iinuma S, Yamasaki M et al. Imaging extrasynaptic glutamate dynamics in the brain. Proc Natl Acad Sci USA. 2010;107(14):6526–6531. doi:10.1073/pnas.0913154107Okubo Y, Sekiya H, Namiki S, Sakamoto H, Iinuma S, Yamasaki M et al. Imaging extrasynaptic glutamate dynamics in the brain. Proc Natl Acad Sci USA. 2010;107(14):6526–6531. doi:10.1073/pnas.0913154107Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neurotoxicity in cortical cell culture. J Neurosci. 1987;7(2):357–368.Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neurotoxicity in cortical cell culture. J Neurosci. 1987;7(2):357–368.Benveniste H, Drejer J, Schousboe A, Diemer NH. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem. 1984;43(5):1369–1374.Benveniste H, Drejer J, Schousboe A, Diemer NH. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem. 1984;43(5):1369–1374.Meldrum B, Evans M, Griffiths T, Simon R. Ischaemic brain damage: the role of excitatory activity and of calcium entry. Br J Anaesth. 1985;57(1):44–46.Meldrum B, Evans M, Griffiths T, Simon R. Ischaemic brain damage: the role of excitatory activity and of calcium entry. Br J Anaesth. 1985;57(1):44–46.Choi DW, Rothman SM. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci. 1990;13:171–182.Choi DW, Rothman SM. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci. 1990;13:171–182.Wang Y, Qin ZH. Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis. 2010;15(11):1382–1402.Wang Y, Qin ZH. Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis. 2010;15(11):1382–1402.Hugon J, Vallat JM, Dumas M. Role of glutamate and excitotoxicity in neurologic diseases. Rev Neurol. 1996;152(4): 239–248.Hugon J, Vallat JM, Dumas M. Role of glutamate and excitotoxicity in neurologic diseases. Rev Neurol. 1996;152(4): 239–248.Sharp CD, Fowler M, Jackson TH, Houghton J, Warren A, Nanda A et al. Human neuroepithelial cells express NMDA receptors. BMC Neurosci. 2003;4:28.Sharp CD, Fowler M, Jackson TH, Houghton J, Warren A, Nanda A et al. Human neuroepithelial cells express NMDA receptors. BMC Neurosci. 2003;4:28.Karadottir R, Cavelier P, Bergersen LH, Attwell D. NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature. 2005;438(7071):1162–1166.Karadottir R, Cavelier P, Bergersen LH, Attwell D. NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature. 2005;438(7071):1162–1166.Del Valle-Pinero AY, Suckow SK, Zhou Q, Perez FM, Verne GN, Caudle RM. Expression of the N-methyl-D-aspartate receptor NR1 splice variants and NR2 subunit subtypes in the rat colon. Neuroscience. 2007;147(1):164–173.Del Valle-Pinero AY, Suckow SK, Zhou Q, Perez FM, Verne GN, Caudle RM. Expression of the N-methyl-D-aspartate receptor NR1 splice variants and NR2 subunit subtypes in the rat colon. Neuroscience. 2007;147(1):164–173.Burns GA, Stephens KE, Benson JA. Expression of mRNA for the N-methyl-D-aspartate (NMDAR1) receptor by the enteric neurons of the rat. Neurosci Lett. 1994;170(1):87–90.Burns GA, Stephens KE, Benson JA. Expression of mRNA for the N-methyl-D-aspartate (NMDAR1) receptor by the enteric neurons of the rat. Neurosci Lett. 1994;170(1):87–90.Li F, Tsien JZ. Memory and the NMDA receptors. N Engl J Med. 2009;361(3):302–303. doi:10.1056/NEJMcibr0902052Li F, Tsien JZ. Memory and the NMDA receptors. N Engl J Med. 2009;361(3):302–303. doi:10.1056/NEJMcibr0902052Lau CG, Zukin RS. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci. 2007;8(6):413–426.Lau CG, Zukin RS. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci. 2007;8(6):413–426.Levite M. Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren’s syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor’s expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy. J Neural Transm (Vienna). 2014;121(8):1029–1075. doi:10.1007/s00702-014-1193-3Levite M. Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren’s syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor’s expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy. J Neural Transm (Vienna). 2014;121(8):1029–1075. doi:10.1007/s00702-014-1193-3Rosenmund C, Stern-Bach Y, Stevens CF. The tetrameric structure of a glutamate receptor channel. Science. 1998;280 (5369):1596–1599.Rosenmund C, Stern-Bach Y, Stevens CF. The tetrameric structure of a glutamate receptor channel. Science. 1998;280 (5369):1596–1599.Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature. 2005; 438(7065):185–192.Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature. 2005; 438(7065):185–192.Das S, Sasaki YF, Rothe T, Premkumar LS, Takasu M, Crandall JE et al. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature. 1998;393(6683):377–381.Das S, Sasaki YF, Rothe T, Premkumar LS, Takasu M, Crandall JE et al. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature. 1998;393(6683):377–381.Гаппоева М. У., Изыкенова Г. А., Гранстрем О. К., Дамбинова С. А. Экспрессия NMDA нейрецепторов при экспериментальной ишемии. Биохимия. 2003;68(6):849–856.Gappoeva MU, Izykenova GA, Granstrem OK, Dambinova SA. Expression of NMDA neuroreceptors in experimental ischemia. Biochemistry (Mosc). 2003;68(6):696–702. In Russian.Gascon S, Deogracias R, Sobrado M, Roda JM, Renart J, Rodríguez-Peña A et al. Transcription of the NR1 subunit of the N-methyl-D-aspartate receptor is down-regulated by excitotoxic stimulation and cerebral ischemia. J Biol Chem. 2005;280(41):35018–35027.Gascon S, Deogracias R, Sobrado M, Roda JM, Renart J, Rodríguez-Peña A et al. Transcription of the NR1 subunit of the N-methyl-D-aspartate receptor is down-regulated by excitotoxic stimulation and cerebral ischemia. J Biol Chem. 2005;280(41):35018–35027.Gingrich MB, Traynelis SF. Serine proteases and brain damage — is there a link? Trends Neurosci. 2000;23(9):399–407. https://doi.org/10.1016/s0166-2236(00)01617-9Gingrich MB, Traynelis SF. Serine proteases and brain damage — is there a link? Trends Neurosci. 2000;23(9):399–407. https://doi.org/10.1016/s0166-2236(00)01617-9Gascon S, Sobrado M, Roda JM, Rodríguez-Peña A, Díaz-Guerra M. Excitotoxicity and focal cerebral ischemia induce truncation of the NR2A and NR2B subunits of the NMDA receptor and cleavage of the scaffolding protein PSD-95. Mol Psychiatry. 2008;13(1):99–114.Gascon S, Sobrado M, Roda JM, Rodríguez-Peña A, Díaz-Guerra M. Excitotoxicity and focal cerebral ischemia induce truncation of the NR2A and NR2B subunits of the NMDA receptor and cleavage of the scaffolding protein PSD-95. Mol Psychiatry. 2008;13(1):99–114.Dong YN, Waxman EA, Lynch DR. Interactions of postsynaptic density-95 and the NMDA receptor 2 subunit control calpain-mediated cleavage of the NMDA receptor. J Neurosci. 2004;24(49):11035–11045.Dong YN, Waxman EA, Lynch DR. Interactions of postsynaptic density-95 and the NMDA receptor 2 subunit control calpain-mediated cleavage of the NMDA receptor. J Neurosci. 2004;24(49):11035–11045.Dambinova SA, Khounteev GA, Skoromets AA. Multiple panel of biomarkers for TIA/stroke evaluation. Stroke. 2002;33(5):1181–1182. doi:10.1161/01.str.0000014922.83673.86Dambinova SA, Khounteev GA, Skoromets AA. Multiple panel of biomarkers for TIA/stroke evaluation. Stroke. 2002;33(5):1181–1182. doi:10.1161/01.str.0000014922.83673.86Дамбинова С. А., Скоромец А. А., Скоромец А. П. Биомаркеры церебральной ишемии. Разработка, исследование и практика. СПб.: ООО «ИПК Коста», 2013. 336 с.Dambinova SA, Skoromets AA, Skoromets AP. Biomarkers of cerebral ischemia. Development, research and practical implementation. SPb.: OOO “IPK Kosta”, 2013. 336 p. In Russian.Bokesch PM, Izykenova GA, Justice JB, Easley KA, Dambinova SA. NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke. 2006;37(6):1432–1436.Bokesch PM, Izykenova GA, Justice JB, Easley KA, Dambinova SA. NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke. 2006;37(6):1432–1436.Bidari A, Vaziri S, Moazen Zadeh E, Farahmand S, Talachian E. The value of serum NR2 antibody in prediction of post-cardiopulmonary resuscitation survival. Emerg (Tehran). 2015;3(3):89–94.Bidari A, Vaziri S, Moazen Zadeh E, Farahmand S, Talachian E. The value of serum NR2 antibody in prediction of post-cardiopulmonary resuscitation survival. Emerg (Tehran). 2015;3(3):89–94.Huseynova S, Panakhova N, Orujova P, Hasanov S, Guliyev M, Orujov A. Elevated levels of serum sICAM-1 in asphyxiated low birth weight newborns. Sci Rep. 2014;4:6850. doi:10.1038/srep06850Huseynova S, Panakhova N, Orujova P, Hasanov S, Guliyev M, Orujov A. Elevated levels of serum sICAM-1 in asphyxiated low birth weight newborns. Sci Rep. 2014;4:6850. doi:10.1038/srep06850Гусев Е. И., Скворцова В. И., Изыкенова Г. А., Алексеев А. А., Дамбинова С. А. Уровень аутоантител к глутаматным рецепторам в сыворотке крови у больных в остром периоде ишемического инсульта. 1996;96(5):68–72.Gusev EI, Skvortsova VI, Izykenova GA, Alekseev AA, Dambinova SA. The level of autoantibodies to glutamate receptors in the blood serum of patients in the acute period of ischemic stroke. Zhurnal nevrologii i psikhiatrii imeni S. S. Korsakova = Zh Nevrol Psikhiatr S S Korsakova. 1996;96(5):68–72. In Russian.Dambinova SA, Khounteev GA, Izykenova GA, Zavolokov IG, Ilyukhina AY, Skoromets AA. Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Clin Chem. 2003;49(10):1752–1762. doi:10.1373/49.10.1752Dambinova SA, Khounteev GA, Izykenova GA, Zavolokov IG, Ilyukhina AY, Skoromets AA. Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Clin Chem. 2003;49(10):1752–1762. doi:10.1373/49.10.1752Dambinova SA, Bettermann K, Glynn T, Tews M, Olson D, Weissman JD et al. Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. PLoS One. 2012;7(7): e42362. doi:10.1371/journal.pone.0042362Dambinova SA, Bettermann K, Glynn T, Tews M, Olson D, Weissman JD et al. Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. PLoS One. 2012;7(7): e42362. doi:10.1371/journal.pone.0042362Дамбинова С. А., Алиев К. Т., Бондаренко Е. В., Пономарев Г. В., Скоромец А. А., Скоромец А. П. и др. Биомаркеры ишемии головного мозга как новый метод доказательства эффективности нейроцитопротекторов. Журнал неврологии и психиатрии им. C. C. Корсакова. 2017;117(5):62–67. doi:10.17116/jnevro20171175162–67.Dambinova SA, Aliev KT, Bondarenko EV, Ponomarev GV, Skoromets AA, Skoromets AP, et al. The biomarkers of cerebral ischemia as a new method for the validation of the efficacy of cytoprotective therapy. Zhurnal nevrologii i psikhiatrii im. S. S. Korsakova = Zh Nevrol Psikhiatr S S Korsakova. 2017;117(5):62–67. doi:10.17116/jnevro20171175162–67. In Russian.Stanca DM, Mărginean IC, Soriău O, Drago C, Mărginean M, Mureanu DF et al. GFAP and antibodies against NMDA receptor subunit NR2 as biomarkers for acute cerebrovascular diseases. J Cell Mol Med. 2015;19(9):2253–2261. doi:10.1111/jcmm.12614Stanca DM, Mărginean IC, Soriău O, Drago C, Mărginean M, Mureanu DF et al. GFAP and antibodies against NMDA receptor subunit NR2 as biomarkers for acute cerebrovascular diseases. J Cell Mol Med. 2015;19(9):2253–2261. doi:10.1111/jcmm.12614Weissman JD, Khunteev GA, Heath R, Dambinova SA. NR2 antibodies: risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events. J Neurol Sci. 2011;300(1–2):97–102. doi:10.1016/j.jns.2010.09.023Weissman JD, Khunteev GA, Heath R, Dambinova SA. NR2 antibodies: risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events. J Neurol Sci. 2011;300(1–2):97–102. doi:10.1016/j.jns.2010.09.023Klimenko LL, Skalny AV, Turna AA, Tinkov AA, Budanova MN, Baskakov IS et al. Serum trace element profiles, prolactin, and cortisol in transient ischemic attack patients. Biol Trace Elem Res. 2016;172(1):93–100. doi:10.1007/s12011-015-0586-yKlimenko LL, Skalny AV, Turna AA, Tinkov AA, Budanova MN, Baskakov IS et al. Serum trace element profiles, prolactin, and cortisol in transient ischemic attack patients. Biol Trace Elem Res. 2016;172(1):93–100. doi:10.1007/s12011-015-0586-ySkalny AV, Klimenko LL, Turna AA, Budanova MN, Baskakov IS, Savostina MS et al. Serum trace elements are associated with hemostasis, lipid spectrum and inflammatory markers in men suffering from acute ischemic stroke. Metab Brain Dis. 2017;32(3):779–788. doi:10.1007/s11011-017-9967-6Skalny AV, Klimenko LL, Turna AA, Budanova MN, Baskakov IS, Savostina MS et al. Serum trace elements are associated with hemostasis, lipid spectrum and inflammatory markers in men suffering from acute ischemic stroke. Metab Brain Dis. 2017;32(3):779–788. doi:10.1007/s11011-017-9967-6González-García S, González-Quevedo A, Hernandez-Diaz Z, Alvarez Camino L, Peña-Sanchez M, Cordero-Eiriz A et al. Circulating autoantibodies against the NR2 peptide of the NMDA receptor are associated with subclinical brain damage in hypertensive patients with other pre-existing conditions for vascular risk. J Neurol Sci. 2017;375:324–330. doi:10.1016/j.jns.2017.02.028González-García S, González-Quevedo A, Hernandez-Diaz Z, Alvarez Camino L, Peña-Sanchez M, Cordero-Eiriz A et al. Circulating autoantibodies against the NR2 peptide of the NMDA receptor are associated with subclinical brain damage in hypertensive patients with other pre-existing conditions for vascular risk. J Neurol Sci. 2017;375:324–330. doi:10.1016/j.jns.2017.02.028

The authors declare that there are no conflicts of interest present.