nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2011-348nnp-108Research ArticleREVIEWSОБЗОРЫNew possibilities of neuroprotection in ischemic strokeНовые возможности нейропротекции при ишемическом инсультеСергеевД. В.SergeyevD. V.info@ima-press.netПирадовМ. А.PiradovM. A.info@ima-press.netМаксимоваМ. Ю.MaksimovaM. Yu.info@ima-press.netДомашенкоМ. А.DomashenkoM. A.mdomashenko@gmail.comСергееваА. Н.SergeyevaA. N.info@ima-press.netОхтоваФ. Р.OkhtovaF. R.info@ima-press.netНаучный центр неврологии РАМНРоссияNeurology Research Center, Russian Academy of Medical SciencesRussian FederationМосковский государственный медицинский стоматологический университетРоссияMoscow University of Medicine and DentistryRussian Federation20111412201134NO4 (2011)5663Copyright © Sergeyev D.V., Piradov M.A., Maksimova M.Y., Domashenko M.A., Sergeyeva A.N., Okhtova F.R., 20112011Сергеев Д.В., Пирадов М.А., Максимова М.Ю., Домашенко М.А., Сергеева А.Н., Охтова Ф.Р.Sergeyev D.V., Piradov M.A., Maksimova M.Y., Domashenko M.A., Sergeyeva A.N., Okhtova F.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/108

Reperfusion and neuroprotection are two present-day therapy strategies for patients with acute stroke. The paper reviews currently available drugs used for neuroprotection in ischemic strokes in the context of evidence-based medicine.

Реперфузия и нейропротекция — два современных стратегических направления терапии пациентов с острым инсультом. С позиций медицины, основанной на доказательствах, представлен обзор современных препаратов, применяемых с целью нейропротекции при ишемических острых нарушениях мозгового кровообращения.

инсультнейропротекцияstrokeneuroprotectionReferences<div><p>Feigin V.L., Lawes C.M.M., Bennett D.A. et al. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009;8(4):355-69.</p><p>Исмагилов М.Ф., Василевская О.В., Гайфутдинов Р.Т. и др. Оценка эффективности церетона в остром периоде ишемического инсульта. Журн неврол и психиатр 2009;3:35-6.</p><p>Adams H.P., Jr, del Zoppo G., Alberts M.J. et al. Guidelines for the Early Management of Adults With Ischemic Stroke. Stroke 2007;38:1655-711.</p><p>Hacke W. Kaste M., Bluhmki E. et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359(13):1317-29.</p><p>Warlow C., van Gijn J., Dennis M. et al. Stroke: practical management. 3rd ed. Oxford: Blackwell Publishung, 2008;551 р.</p><p>The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7.</p><p>Ginsberg M.D. Current Status of Neuroprotection for Cerebral Ischemia. Synoptic Overview. Stroke 2009;40:S111-S114.</p><p>Feuerstein G.Z., Chavez J. Translational Medicine for Stroke Drug Discovery: The Pharmaceutical Industry Perspective. Stroke 2009;40:S121-S125.</p><p>O'Collins V.E., Macleod M.R., Donnan G.A. et al. 1026 experimental treatments in acute stroke. Ann Neurol 2006;59:467-77</p><p>Martinez-Vila E., Sieira P. Current status and perspectives of neuroprotection in ischemic stroke treatment. Cerebrovasc Dis 2001;11(Suppl. 1):60-70.</p><p>Philip M., Benatar M., Fisher M. et al. Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials. Stroke 2009;40(2):577-81.</p><p>Lees K.R., Zivin J.A., Ashwood T. et al. NXY-059 for acute ischemic stroke. N Engl J Med 2006;354:588-600.</p><p>Shuaib A., Lees K.R., Lyden P. et al. NXY059 for the treatment of acute ischemic stroke. N Engl J Med 2007;357:562-71.</p><p>Savitz S.I., Fisher M. Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials. Ann Neurol 2007;61(5):396-402.</p><p>Green A.R., Odergren T, Ashwood T. Animal models of stroke: do they have value for discovering neuroprotective agents. Trends Pharmacol Sci 2003;24:402-8.</p><p>Stroke Therapy Academic Industry Roundtable. Recommendations for standards regarding pre-clinical neuroprotective and restorative drug development. Stroke 1999;30:2752-8.</p><p>Stroke Therapy Academic Industry Roundtable II. Stroke Therapy Academic Industry Roundtable II (STAIR-II). Stroke 2001;32:1598-606.</p><p>Bernard S.A., Gray T.W., Buist M.D. et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63.</p><p>Ovbiagele B., Kidwell C.S., Starkman S.et al. Neuroprotective agents for the treatment of acute ischemic stroke. Curr Neurol Neurosci Rep 2003;3:9-20.</p><p>Muir K.W., Ford I., Reid J.L. et al. Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet 2004;363:439-45.</p><p>Saver J.L., Eckstein M., Stratton S.J. et al. for the FAST-MAG Investigators. The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Phase 3 Clinical Trial. Ongoing Clinical Trial Poster Session Abstract Book, 29th International Stroke Conference, San Diego, CA, February 5, 2004.</p><p>Muller W.E., Mь ller W.E., Eckert G.P. et al. Piracetam: novelty in a unique mode of action. Pharmacopsychiatry 1999;32:2-9.</p><p>Winblad B. Piracetam: a review of pharmacological properties and clinical uses. CNS. Drug Rev 2005;11:169-82.</p><p>De Deyn P.P., Reuck J.D., Deberdt W. et al. Treatment of acute ischemic stroke with piracetam. Members of the Piracetam in Acute Stroke Study (PASS) Group. Stroke 1997;28:2347-52.</p><p>Луцкий М.А. Анализ эффективности мексидола в комплексном лечении больных с ишемическим инсультом. Журн неврол и психиатр 2010;57-9.</p><p>Румянцева С.А., Евсеев В.Н., Елисеев Е.В. Антиоксидантная терапия при остром ишемическом инсульте. Атмосфера. Нервн бол 2009;8-12.</p><p>Скворцова В.И., Стаховская Л.В., Нарциссов Я.Р. и др. Рандомизированное двойное слепое плацебоконтролируемое исследование эффективности и безопасности мексидола в комплексной терапии ишемического инсульта в остром периоде. Инсульт. Неврол и психиатр 2006;(прил. 18):47-54.</p><p>Parnetti L., Amenta F., Gallai V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev 2001;122(16):2041-55.</p><p>Barbagallo Sangiorgi G., Barbagallo M, Giordano M. et al. alpha-lycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci 1994;717:253-69.</p><p>Одинак М.М., Вознюк И.А., Пирадов М.А. и др. Многоцентровое (пилотное) исследование эффективности глиатилина при остром ишемическом инсульте. Анн клин и эксперим неврол 2010;1:20-8.</p><p>Tatebayashi Y., Lee M.H., Li L. et al. The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease. Acta Neuropathol 2003;105:225-32.</p><p>Ren J.M., Sietsma D., Qiu S. et al. Cerebrolysin enhances functional recovery following focal cerebral infarction in rats. Restor Neurol Neurosci 2007;25:25-31.</p><p>Haffner Z. Cerebrolysin in acute ischemic stroke. Cephalalgia Hung 1999;5:52-3.</p><p>Ladurner G., Kalvach P., Moessler H. et al. Neuroprotective treatment with cerebrolysin in patients with acute stroke: a randomised controlled trial. J Neural Transm 2005;112:415-28.</p><p>Hong Z., Moessler H., Bornstein N. et al. A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia-CASTA. Int J Stroke 2009;4(5):406-12.</p><p>Ziganshina L.E., Abakumova T., Kuchaeva A. Cerebrolysin for acute ischaemic stroke. Cochrane Database Syst Rev 2010(4):CD007026.</p><p>Heiss W.-D. Cerebrolysin in patients with acute ischemic stroke - the CASTA study. 7th World Stroke Congress, Plenary III: Large Clinical Trials Closing Session. Presented October 16, 2010.</p><p>Tazaki Y., Sakai F., E Otomo E. et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 1988;19(2):211-6.</p><p>Clark W.M., Warach S.J., Pettigrew L.C. et al. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group. Neurology 1997;49(3):671-8.</p><p>Clark W.M., Williams B. J., Selzer K. A. et al. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 1999;30(12):2592-7.</p><p>Clark W.M., Wechsler L.R., Sabounjian L.A. et al. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 2001;57(9):1595-602.</p><p>Dаvalos A., Castillo J., Alvarez-Sabin J. et al. Oral Citicoline in Acute Ischemic Stroke: An Individual Patient Data Pooling Analysis of Clinical Trials. Stroke 2002;33:2850-7.</p><p>Saver J.L., Wilterdink J. Choline precursors in acute and subacute human stroke: a metaanalysis. Stroke 2002;33:353.</p><p>Bolland K., Whitehead J., Cobo E. et al. Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline. Pharm Stat 2009;8(2):136-49.</p><p>Belayev L., Liu Y., Zhao V. et al. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke 2001;32:553-60.</p><p>Ginsberg M.D., Palesch Y.Y., Martin R.H. et al. The albumin in acute stroke (ALIAS) multicenter clinical trial: safety analysis of part and rationale and design of part 2. Stroke 2011;42(1):119-27.</p><p>Gutiеrrez M., Merino J.J., de Lecinana M.A. et al. Cerebral protection, brain repair, plasticity and cell therapy in ischemic stroke. Cerebrovasc Dis 2009;27(Suppl. 1):177-86.</p><p>Kondziolka D., Villemagne V.L., Wechsler L. et al. Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg, 2005;103:38-45.</p><p>Kondziolka D., Wechsler L., Goldstein S. et al. Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000;55:565-9.</p><p>Bang O.Y., Lee J.S., Lee P.H. et al. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005;57:874-82.</p><p>Пирадов М.А., Сергеев Д.В., Танашян М.М. Применение клеток пуповинной крови в реабилитации пациентов, перенесших ишемический инсульт. В кн.: Терапевтический потенциал клеток пуповинной крови при негематологических заболеваниях. Под ред. М.А. Пальцева, В.Н. Смирнова. М.: Медицина, 2011;126-33.</p><p>Kammersgaard L.P., Rasmussen B. H., Jorgensen H.S. et al. Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: A case-control study: the Copenhagen Stroke Study. Stroke 2000;31:2251-6.</p><p>De Georgia M.A., Krieger D. W., AbouChebl A. et al. Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology 2004;63:312-7.</p><p>Guluma K.Z., Hemmen T.M., Olsen S.E. et al. A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology. Acad Emerg Med 2006;13:820-7.</p><p>Froehler M.T., Ovbiagele B. Therapeutic hypothermia for acute ischemic stroke. Expert Rev Cardiovasc Ther 2010;8(4):593-603.</p><p>Van der Worp H.B., Macleod M. R., Kollmar R. Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials- J Cereb Blood Flow Metab 2010;30(6):1079-93.</p><p>Yenari M.A., Hemmen T.M. Therapeutic hypothermia for brain ischemia: where have we come and where do we go- Stroke 2010;41(Suppl. 10):S72-4.</p><p>Hemmen T.M., Raman R., Guluma K.Z. et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuSL): final results. Stroke 2010;41(10):2265-70.</p><p>Donnan G.A., Davis S.M. Parsons M.W. et al. How to make better use of thrombolytic therapy in acute ischemic stroke. Nat Rev Neurol 2011;7(7):400-9.</p><p>Chavez J.C., Hurko O., Barone F.C. et al. Pharmacologic interventions for stroke: looking beyond the thrombolysis time window into the penumbra with biomarkers, not a stopwatch. Stroke 2009;40(10):e558-е563.</p><p>Sutherland B.A., Papadakis M., Chen R.-L. et al. Cerebral blood flow alteration in neuroprotection following cerebral ischaemia. J Physiol 2011;589(Pt 17):4105-14.</p><p>Lu M. Assessing combination treatments in acute stroke: preclinical experiences. Behav Brain Res 2005;162(2):165-72.</p><p>Amaro S., Canovas D., Castellanos M. et al. The URICO-ICTUS study, a phase 3 study of combined treatment with uric acid and rtPA administered intravenously in acute ischaemic stroke patients within the first 4.5 h of onset of symptoms. Int J Stroke 2010;5(4):325-8.</p><p>Logallo N., Naess H., Idicula T.T. et al. Serum uric acid: neuroprotection in thrombolysis. The Bergen NORSTROKE study. BMC Neurol 2011;11:114.</p></div><br /><div><p>Feigin V.L., Lawes C.M.M., Bennett D.A. et al. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009;8(4):355-69.</p><p>Исмагилов М.Ф., Василевская О.В., Гайфутдинов Р.Т. и др. Оценка эффективности церетона в остром периоде ишемического инсульта. Журн неврол и психиатр 2009;3:35-6.</p><p>Adams H.P., Jr, del Zoppo G., Alberts M.J. et al. Guidelines for the Early Management of Adults With Ischemic Stroke. Stroke 2007;38:1655-711.</p><p>Hacke W. Kaste M., Bluhmki E. et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359(13):1317-29.</p><p>Warlow C., van Gijn J., Dennis M. et al. Stroke: practical management. 3rd ed. Oxford: Blackwell Publishung, 2008;551 р.</p><p>The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7.</p><p>Ginsberg M.D. Current Status of Neuroprotection for Cerebral Ischemia. Synoptic Overview. Stroke 2009;40:S111-S114.</p><p>Feuerstein G.Z., Chavez J. Translational Medicine for Stroke Drug Discovery: The Pharmaceutical Industry Perspective. Stroke 2009;40:S121-S125.</p><p>O'Collins V.E., Macleod M.R., Donnan G.A. et al. 1026 experimental treatments in acute stroke. Ann Neurol 2006;59:467-77</p><p>Martinez-Vila E., Sieira P. Current status and perspectives of neuroprotection in ischemic stroke treatment. Cerebrovasc Dis 2001;11(Suppl. 1):60-70.</p><p>Philip M., Benatar M., Fisher M. et al. Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials. Stroke 2009;40(2):577-81.</p><p>Lees K.R., Zivin J.A., Ashwood T. et al. NXY-059 for acute ischemic stroke. N Engl J Med 2006;354:588-600.</p><p>Shuaib A., Lees K.R., Lyden P. et al. NXY059 for the treatment of acute ischemic stroke. N Engl J Med 2007;357:562-71.</p><p>Savitz S.I., Fisher M. Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials. Ann Neurol 2007;61(5):396-402.</p><p>Green A.R., Odergren T, Ashwood T. Animal models of stroke: do they have value for discovering neuroprotective agents. Trends Pharmacol Sci 2003;24:402-8.</p><p>Stroke Therapy Academic Industry Roundtable. Recommendations for standards regarding pre-clinical neuroprotective and restorative drug development. Stroke 1999;30:2752-8.</p><p>Stroke Therapy Academic Industry Roundtable II. Stroke Therapy Academic Industry Roundtable II (STAIR-II). Stroke 2001;32:1598-606.</p><p>Bernard S.A., Gray T.W., Buist M.D. et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63.</p><p>Ovbiagele B., Kidwell C.S., Starkman S.et al. Neuroprotective agents for the treatment of acute ischemic stroke. Curr Neurol Neurosci Rep 2003;3:9-20.</p><p>Muir K.W., Ford I., Reid J.L. et al. Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet 2004;363:439-45.</p><p>Saver J.L., Eckstein M., Stratton S.J. et al. for the FAST-MAG Investigators. The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Phase 3 Clinical Trial. Ongoing Clinical Trial Poster Session Abstract Book, 29th International Stroke Conference, San Diego, CA, February 5, 2004.</p><p>Muller W.E., Mь ller W.E., Eckert G.P. et al. Piracetam: novelty in a unique mode of action. Pharmacopsychiatry 1999;32:2-9.</p><p>Winblad B. Piracetam: a review of pharmacological properties and clinical uses. CNS. Drug Rev 2005;11:169-82.</p><p>De Deyn P.P., Reuck J.D., Deberdt W. et al. Treatment of acute ischemic stroke with piracetam. Members of the Piracetam in Acute Stroke Study (PASS) Group. Stroke 1997;28:2347-52.</p><p>Луцкий М.А. Анализ эффективности мексидола в комплексном лечении больных с ишемическим инсультом. Журн неврол и психиатр 2010;57-9.</p><p>Румянцева С.А., Евсеев В.Н., Елисеев Е.В. Антиоксидантная терапия при остром ишемическом инсульте. Атмосфера. Нервн бол 2009;8-12.</p><p>Скворцова В.И., Стаховская Л.В., Нарциссов Я.Р. и др. Рандомизированное двойное слепое плацебоконтролируемое исследование эффективности и безопасности мексидола в комплексной терапии ишемического инсульта в остром периоде. Инсульт. Неврол и психиатр 2006;(прил. 18):47-54.</p><p>Parnetti L., Amenta F., Gallai V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev 2001;122(16):2041-55.</p><p>Barbagallo Sangiorgi G., Barbagallo M, Giordano M. et al. alpha-lycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci 1994;717:253-69.</p><p>Одинак М.М., Вознюк И.А., Пирадов М.А. и др. Многоцентровое (пилотное) исследование эффективности глиатилина при остром ишемическом инсульте. Анн клин и эксперим неврол 2010;1:20-8.</p><p>Tatebayashi Y., Lee M.H., Li L. et al. The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease. Acta Neuropathol 2003;105:225-32.</p><p>Ren J.M., Sietsma D., Qiu S. et al. Cerebrolysin enhances functional recovery following focal cerebral infarction in rats. Restor Neurol Neurosci 2007;25:25-31.</p><p>Haffner Z. Cerebrolysin in acute ischemic stroke. Cephalalgia Hung 1999;5:52-3.</p><p>Ladurner G., Kalvach P., Moessler H. et al. Neuroprotective treatment with cerebrolysin in patients with acute stroke: a randomised controlled trial. J Neural Transm 2005;112:415-28.</p><p>Hong Z., Moessler H., Bornstein N. et al. A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia-CASTA. Int J Stroke 2009;4(5):406-12.</p><p>Ziganshina L.E., Abakumova T., Kuchaeva A. Cerebrolysin for acute ischaemic stroke. Cochrane Database Syst Rev 2010(4):CD007026.</p><p>Heiss W.-D. Cerebrolysin in patients with acute ischemic stroke - the CASTA study. 7th World Stroke Congress, Plenary III: Large Clinical Trials Closing Session. Presented October 16, 2010.</p><p>Tazaki Y., Sakai F., E Otomo E. et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 1988;19(2):211-6.</p><p>Clark W.M., Warach S.J., Pettigrew L.C. et al. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group. Neurology 1997;49(3):671-8.</p><p>Clark W.M., Williams B. J., Selzer K. A. et al. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 1999;30(12):2592-7.</p><p>Clark W.M., Wechsler L.R., Sabounjian L.A. et al. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 2001;57(9):1595-602.</p><p>Dаvalos A., Castillo J., Alvarez-Sabin J. et al. Oral Citicoline in Acute Ischemic Stroke: An Individual Patient Data Pooling Analysis of Clinical Trials. Stroke 2002;33:2850-7.</p><p>Saver J.L., Wilterdink J. Choline precursors in acute and subacute human stroke: a metaanalysis. Stroke 2002;33:353.</p><p>Bolland K., Whitehead J., Cobo E. et al. Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline. Pharm Stat 2009;8(2):136-49.</p><p>Belayev L., Liu Y., Zhao V. et al. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke 2001;32:553-60.</p><p>Ginsberg M.D., Palesch Y.Y., Martin R.H. et al. The albumin in acute stroke (ALIAS) multicenter clinical trial: safety analysis of part and rationale and design of part 2. Stroke 2011;42(1):119-27.</p><p>Gutiеrrez M., Merino J.J., de Lecinana M.A. et al. Cerebral protection, brain repair, plasticity and cell therapy in ischemic stroke. Cerebrovasc Dis 2009;27(Suppl. 1):177-86.</p><p>Kondziolka D., Villemagne V.L., Wechsler L. et al. Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg, 2005;103:38-45.</p><p>Kondziolka D., Wechsler L., Goldstein S. et al. Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000;55:565-9.</p><p>Bang O.Y., Lee J.S., Lee P.H. et al. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005;57:874-82.</p><p>Пирадов М.А., Сергеев Д.В., Танашян М.М. Применение клеток пуповинной крови в реабилитации пациентов, перенесших ишемический инсульт. В кн.: Терапевтический потенциал клеток пуповинной крови при негематологических заболеваниях. Под ред. М.А. Пальцева, В.Н. Смирнова. М.: Медицина, 2011;126-33.</p><p>Kammersgaard L.P., Rasmussen B. H., Jorgensen H.S. et al. Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: A case-control study: the Copenhagen Stroke Study. Stroke 2000;31:2251-6.</p><p>De Georgia M.A., Krieger D. W., AbouChebl A. et al. Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology 2004;63:312-7.</p><p>Guluma K.Z., Hemmen T.M., Olsen S.E. et al. A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology. Acad Emerg Med 2006;13:820-7.</p><p>Froehler M.T., Ovbiagele B. Therapeutic hypothermia for acute ischemic stroke. Expert Rev Cardiovasc Ther 2010;8(4):593-603.</p><p>Van der Worp H.B., Macleod M. R., Kollmar R. Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials- J Cereb Blood Flow Metab 2010;30(6):1079-93.</p><p>Yenari M.A., Hemmen T.M. Therapeutic hypothermia for brain ischemia: where have we come and where do we go- Stroke 2010;41(Suppl. 10):S72-4.</p><p>Hemmen T.M., Raman R., Guluma K.Z. et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuSL): final results. Stroke 2010;41(10):2265-70.</p><p>Donnan G.A., Davis S.M. Parsons M.W. et al. How to make better use of thrombolytic therapy in acute ischemic stroke. Nat Rev Neurol 2011;7(7):400-9.</p><p>Chavez J.C., Hurko O., Barone F.C. et al. Pharmacologic interventions for stroke: looking beyond the thrombolysis time window into the penumbra with biomarkers, not a stopwatch. Stroke 2009;40(10):e558-е563.</p><p>Sutherland B.A., Papadakis M., Chen R.-L. et al. Cerebral blood flow alteration in neuroprotection following cerebral ischaemia. J Physiol 2011;589(Pt 17):4105-14.</p><p>Lu M. Assessing combination treatments in acute stroke: preclinical experiences. Behav Brain Res 2005;162(2):165-72.</p><p>Amaro S., Canovas D., Castellanos M. et al. The URICO-ICTUS study, a phase 3 study of combined treatment with uric acid and rtPA administered intravenously in acute ischaemic stroke patients within the first 4.5 h of onset of symptoms. Int J Stroke 2010;5(4):325-8.</p><p>Logallo N., Naess H., Idicula T.T. et al. Serum uric acid: neuroprotection in thrombolysis. The Bergen NORSTROKE study. BMC Neurol 2011;11:114.</p></div><br />

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