Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9533910.26442/20751753.2020.9.200284ArticlesСтатьиReview ArticleThe role of blood biomarkers in predicting the outcome of ischemic strokeРоль биомаркеров крови в прогнозировании исхода течения ишемического инсультаGulievaMaiia S.ГулиеваМайя Шохлатовна

ст. лаборант, каф. неврологии, нейрохирургии и медицинской генетики лечебного фак-та

m.gulieva2014@yandex.ruBagmanianSona D.БагманянСона Дживановна

ст. лаборант, каф. неврологии, нейрохирургии и медицинской генетики лечебного фак-та

ChukanovaAnna S.ЧукановаАнна Сергеевна

канд. мед. наук, доц. каф. неврологии, нейрохирургии и медицинской генетики лечебного фак-та

ChukanovaElena I.ЧукановаЕлена Игоревна

д-р мед. наук, проф. каф. неврологии, нейрохирургии и медицинской генетики лечебного фак-та

Pirogov Russian National Research Medical UniversityФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России15092020229VOL 9, NO22 (2020)ТОМ 22, №9 (2020)283228122021Copyright ©; 2020, Consilium MedicumCopyright ©; 2020, ООО "Консилиум Медикум"2020Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95339

Stroke is one of the most common neurological diseases and the third cause of patient disability. More than 5 million people die from stroke worldwide annually, and every 6th patient survived has a second stroke for the next 5 years. Over the past two decades, mortality from this disease has been declining, but the percentage of disability remains very high. Today, predicting the course of stroke is an important field of scientific development, which will allow to elaborate optimal therapeutic approaches and individualized rehabilitation programs. One of the promising directions for predicting the course of cerebral ischemia is the use of biomarkers, the role of which is being studied, and their further research is relevant for the possibility of their use in clinical practice.

Инсульт является одним из наиболее распространенных неврологических заболеваний и третьей причиной инвалидизации пациентов. Ежегодно во всем мире от инсульта умирают более 5 млн человек, и каждый 6-й выживший пациент в течение последующих 5 лет переносит повторный инсульт. За последние два десятилетия отмечается снижение уровня смертности от данного заболевания, однако процент инвалидизации остается еще очень высоким. В настоящее время актуальным направлением научных разработок является прогнозирование течения инсульта, которое позволит разрабатывать оптимальные терапевтические подходы и разрабатывать индивидуальные программы реабилитационного лечения. Одним из перспективных направлений для прогнозирования течения ишемии мозга является использование биомаркеров, изучение роли которых находится в стадии разработки, и их дальнейшие исследования актуальны для возможности их применения в клинической практике врача.

brain ischemiaischemic strokeblood-brain barrierneurospecific proteinsblood biomarkersneuron-specific enolasebrain neurotrophic factorprotein p53ишемия мозгаишемический инсультгематоэнцефалический барьернейроспецифические белкибиомаркеры кровинейронспецифическая енолазамозговой нейротрофический факторбелок р53Feigin VL, Norrving B, Mensah GA. Global burden of stroke. Circ Res 2017; 120 (3): 439-48. DOI: 10.1161/CIRCRESAHA.116.308413Рябухин И.А. Нейроспецифические белки в оценке проницаемости гематоэнцефалического барьера человека и животных. Дис.. д-ра мед. наук. М., 2004.Блинов Д.В. Современные представления о роли нарушения резистентности гематоэнцефалического барьера в патогенезе заболеваний ЦНС. Часть 2: функции и механизмы повреждения гематоэнцефалического барьера. Эпилепсия и пароксизмальные состояния. 2014; 6 (1): 70-84.Fischer S, Clauss M, Wiesnet M et al. Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO. Am J Physiol 1999; 276: 812-20.Schaarschmidt H, Prange HW, Reiber H. Neuron-specific enolase concentrations in blood as a prognostic parameter in cerebrovascular diseases. Stroke 1994; 25: 558-65.Barone FC, Clerk RK, Price W. Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia. Brain Res 1993; 1: 71-82.Herrmann M, Jost S, Kutz S et al. Temporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography. J Neurotrauma 2000; 17: 113-22.Herrmann M, Elirenreich H. Brain derived proteins as markers of acute stroke: their relation to pathophysiology, outcome prediction and neuroprotective drug monitoring. Restor Neurol Neurosci 2003;21: 177-90.Chekhonin VP, Zhirkov YA, Belyaeva IA et al. Serum time course of two brain-specific proteins, alpha(l) brain globulin and neuron-specific enolase, in tick-born encephalitis and Lyme disease. Clin Chim Acta 2002; 320: 117-25.Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Ne-urochem Res 2000; 25: 1439-51.Engvall E, Perlman P Enzyme-linked immunoadsorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochem 1971; 8: 871-9.Чехонин В.П., Жирков Ю.А., Турина О.И. и др. Количественно-кинетические параметры элиминации нейроспецифических антигенов и антител к ним при некоторых нервно-психических заболеваниях. Рос.психиатрич. журн.2000;3:4-8.Perry LA, Lucarelli T, Penny-Dimri JC et al. Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy. Int J Stroke 2019; 14 (4): 390-9. DOI: 10.1177/1747493018806167Nylen K, Csajbok LZ, Ost M et al. Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage. Stroke 2007; 38 (5): 1489-94.Moore BW. A soluble protein characteristic of the nervous system. Biochem Biophys Res Commun 1965; 19: 739-44.Donato R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 2001; 33: 637-68.Saengen AK, Christenson RN. Stroke Biomarkers: Progress and Challenges for Diagnosis, Prognosis, Differentiation and Treatment. Clin Chem 2010; 56 (1): 21-33.Harish Kumar, Manoj Lakhotia, Hansraj Pahadiya, Jagdish Singh. To study the correlation of serum S-100 protein level with the severity of stroke and its prognostic implication. J Neurosci Rural Pract 2015; 6 (3): 326-30. DOI: 10.4103/0976-3147.158751Foerch C, Singer OC, Neumann-Haefelin T et al. Evaluation of serum S100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction. Arch Neurol 2005; 62 (7): 1130-4.Dassan P, Keir G, Brown MM. Criteria for a clinically informative serum biomarker in acute ischaemic stroke: a review of S100B. Cerebrovasc Dis 2009; 27 (3): 295-302. DOI: 10.1159/000199468Hatfield R, McKernan R. CSF neuron-specific enolase as a quantitative marker of neuronal damage in a rat stroke model. Brain Res 1992; 577: 249-52.Woertgen C, Rothoerl RD, Brawanski A. Neuron-specific enolase serum levels after controlled cortical impact injury in the rat. J Neurotrauma 2001; 18: 569-73.Haupt WF, Chopan G, Sobesky J et al. Prognostic value of somatosensory evoked potentials, neuron-specific enolase, and S100 for short-term outcome in ischemic stroke. J Neurophysiol 2016; 115: 1273-8.Stevens H, Jakobs C, de Jager AE et al. Neurone-specific enolase and N-acetyl-aspartate as potential peripheral markers of ischaemic stroke. Eur J Clin Invest 1999; 29: 6-11.Schaarschmidt H, Prange HW, Reiber H. Neuron-specific enolase concentrations in blood as a prognostic parameter in cerebrovascular diseases. Stroke 1994; 25: 558-65.Bharosay A, Bharosay VV, Varma M et al. Correlation of brain biomarker Neuron specific enolase (NSE) with degree of disability and neurological worsening in cerebrovascular stroke. Indian J Clin Biochem 2012; 27 (2): 186-90.Wunderlich MT, Ebert AD, Kratz T et al. Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage. Stroke 1999; 30: 1190-5.Hill MD, Jackowski G, Bayer N et al. Biochemical markers in acute ischemic stroke. CMAJ 2000; 162:1139-40.Fassbender K, Schmidt R, Schreiner A et al. Leakage of brain-originated proteins in peripheral blood: temporal profile and diagnostic value in early ischemic stroke. J Neurol Sci 1997; 148 (1): 101-5.Cunningham RT, Watt M, Winder J et al. Serum neurone-specific enolase as an indicator of stroke volume. Eur J Clin Invest 1996; 26 (4): 298-303.Cunningham RT, Young IS, Winder J et al. Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction. Eur J Clin Invest 1991; 21 (5): 497-500.Missler U, Wiesmann M, Friedrich C, Kaps M. S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. Stroke 1997; 28 (10): 1956-60.Hasan N, McColgan P, Bentley P et al. Towards the identification of blood biomarkers for acute stroke in humans: a comprehensive systematic review. Br J Clin Pharmacol 2012; 74: 230-40.Martinez-Sanchez P, Gutierrez-Fernandez M, Fuentes B et al. Biochemical and inflammatory biomarkers in ischemic stroke: translational study between humans and two experimental rat models. J Transl Med 2014; 12: 220.Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev 2007; 4: 34-66. https://doi.org/10.1016Zj.brainresrev.2006.11.003Niu FN, Zhang X, Hu XM et al. Targeted mutation of Fas ligand gene attenuates brain inflammation in experimental stroke. Brain Behavior Immunity 2012; 26 (1): 61-71. DOI: 10.1016/j.bbi.2011.07.235Mahovic D, Zurak N, Lakusic N et al. The dynamics of soluble Fas/APO 1 apoptotic biochemical marker in acute ischemic stroke patients. Adv Med Sci 2013; 58 (2): 298-303. DOI: 10.2478/ams-2013-0014Сергеева С.П., Савин А.А., Архипов В.В. и др. Прогнозирование исхода острого периода ишемического инсульта: роль маркеров апоптоза. Клиническая неврология. 2017; 11 (1): 21-7.Чумаков П.М. Белок р53 и его универсальные функции в многоклеточном организме. Успехи биологической химии. 2007; 47: 3-52.Stanne TM, Aberg ND, Nilsson S et al. Low circulating acute brain-derived neurotrophic factor levels are associated with poor long-term functional outcome after ischemic stroke. Stroke 2016; 47 (7): 1943-5.Filichia E, Shen H, Zhou X et al. Forebrain neuronal specific ablation of p53 gene provides protection in a cortical ischemic stroke model. J Neuroscience 2015; 295: 1-10.Кольцова К.В. Роль полиморфных вариантов генов, участвующих в рецепторном пути индукции апоптоза (FADD, Fas и каспазы-8) в патогенезе ишемического инсульта. Дис.. канд. мед. наук. М., 2007.Чернышева Е.Н., Панова Т.Н. Индуктор апоптоза - белок р53 и инсулинорезистентность при метаболическом синдроме. Кубанский науч. мед. вестн. 2012; 131 (2): 186-90.Matsuo R, Ago T Kamouchi M et al. Clinical significance of plasma VEGF value in ischemic stroke -Research for biomarkers in ischemic stroke (rebios) study. BMC Neurol 2013; 13: 32.Lee SC, Lee KY, Kim YJ et al. Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis. Eur J Neurol 2010; 17: 45-51.Putaala J, Metso AJ, Metso TM et al. Analysis of 1008 Consecutive Patients Aged 15 to 49 With First-Ever Ischemic Stroke: The Helsinki Young Stroke Registry. Stroke 2009; 40: 1195-203.Kumar S, Parkash J, Kataria H, Kaur G. Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain. Neurosci Res 2009; 65 (4): 367-74.Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol 2005; 76 (2): 99-125.Walz C, Jungling K, Lessmann V, Gottmann K. Presynaptic plasticity in an immature neocortical network requires NMDA receptor activation and BDNF release. J Neurophysiol 2006; 96: 3512-6.Kramar EA, Chen LY, Lauterborn JC et al. BDNF upregulation rescues synaptic plasticity in middleaged ovariectomized rats. Neurobiol Aging 2010; 33: 708-19.Yamashita K, Wiessner C, Lindholm D et al. Post-41 occlusion treatment with BDNF reduces infarct size in a model of permanent occlusion of 42 the middle cerebral artery in rat. Metab Brain Dis 1997; 12: 271-80.Schabitz WR, Berger C, Kollmar R et al. Effect of brain-derived neurotrophic factor treatment and forced arm 24 use on functional motor recovery after small cortical ischemia. Stroke 2004; 35: 992-7.Jiang Y, Wei N, Zhu J et al. Effects of brainderived neurotrophic factor on local inflammation in experimental stroke of rat. Mediat Inflamm 2010; 2010: 1-10.Bus BA, Molendijk ML, Penninx BJ et al. Determinants of serum brain-derived neurotrophic factor. Psychoneuroendocrinology 2011; 36: 228-39.McAllister AK, Lo DC, Katz LC. Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 1995; 15: 791-803.Lee J, Seroogy KB, Mattson MP. Dietary restriction enhances neurotrophins expression and neurogenesis in the hippocampus of adult mice. J Neurochem 2002; 80 (3): 539-47.Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci 2005; 6 (8): 603-14.Yang L, Zhang Z, Sun D et al. Low serum BDNF may indicate the development of PSD in patients with acute ischemic stroke. Int J Geriatr Psychiatry 2011; 26 (5): 495-502.Еремова Н.М. Роль «отдаленных последствий ишемии» (нейротрофической дисфункции, аутоиммунной и воспалительной реакций) в патогенезе ишемического инсульта. Дис. канд. мед. наук. М., 2003.Pikula A, Beiser AS, Chen TC et al. Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury: Framingham Study. Stroke 2013; 44: 2768-75.Hope TM, Seghier ML, Leff AP, Price CJ. Predicting outcome and recovery after stroke with lesions extracted from MRI images. Neuroimage Clin 2013; 2: 424-33.Luan X, Qiu H, Hong X et al. High serum nerve growth factor concentrations are associated with good functional outcome at 3 months following acute ischemic stroke. Clin Chim Acta 2019; 488: 20-4. DOI: 10.1016/j.cca.2018.10.030Lai YJ, Hanneman SK, Casarez RL et al. Blood biomarkers for physical recovery in ischemic stroke: a systematic review. Am J Transl Res 2019; 11 (8): 4603-13.