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Перспективные направления нейропротекции при ишемическом инсульте в эксперименте и клинике
Котов С.В., Исакова Е.В., Сидорова О.П., Белова Ю.А. Перспективные направления нейропротекции при ишемическом инсульте в эксперименте и клинике. Consilium Medicum. 2016; 18 (9): 45–48. DOI: 10.26442/2075-1753_2016.9.45-48
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Kotov S.V., Isakova E.V., Sidorova O.P., Belova Yu.A. Prospective experimental and clinical trends of neuroprotection in ischemic stroke. Consilium Medicum. 2016; 18 (9): 45–48. DOI: 10.26442/2075-1753_2016.9.45-48
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Аннотация
Обзор посвящен современным тенденциям нейропротекции при ишемическом инсульте. В настоящее время выработаны новые правила проведения подобных исследований, они проводятся на базе знаний об ишемическом каскаде и нейроваскулярной единице. Рассмотрены результаты экспериментальных и клинических исследований препаратов, обладающих нейропротективным действием. Особое внимание уделено факторам роста и сходным веществам.
Ключевые слова: инсульт, ишемический каскад, нейропротекция, нейроваскулярная единица, протеин, фактор роста.
Ключевые слова: инсульт, ишемический каскад, нейропротекция, нейроваскулярная единица, протеин, фактор роста.
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The review is devoted to modern trends of neuroprotection in ischemic stroke. At this time the new rules were developed for the conducting of such studies, they are conducted on the basis of the knowledge of the ischemic cascade and the neurovascular unit. The results of experimental and clinical studies of drugs with neuroprotective effect are discussed. Special attention is paid to growth factors and similar substances.
Key words: stroke, ischemic cascade, neuroprotection, neurovascular unit, protein, growth factor.
Key words: stroke, ischemic cascade, neuroprotection, neurovascular unit, protein, growth factor.
Полный текст
Список литературы
1. Powers WJ, Derdeyn CP, Biller J et al. American Heart Association Stroke Council. 2015 AHA/ASA focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals fr om the American heart association/American stroke association. Stroke 2015; 46 (10): 3020–35. Doi:10.1161/STR.0000000000000074.
2. Espinosa de Rueda M, Parrilla G, Manzano-Fernández S et al. Combined multimodal computed tomography score correlates with futile recanalization after thrombectomy in patients with acute stroke. Stroke 2015; 46 (9): 2517–22. Doi: 10.1161/STROKEAHA.114.008598.
3. Gomis M, Dávalos A. Recanalization and reperfusion therapies of acute ischemic stroke: what have we learned, what are the major research questions, and wh ere are we headed? Front Neurol 2014; 5: 226. Doi: 10.3389/fneur.2014.00226. eCollection 2014.
4. Savitz SI, Fisher M. Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials. Ann Neurol 2007; 61 (5): 396–402.
5. Fisher M, Feuerstein G, Howells DW et al. STAIR Group. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009; 40 (6): 2244–50. Doi: 10.1161/STROKEAHA.108.541128.
6. Vivien D, Gauberti M, Montagne A et al. Impact of tissue plasminogen activator on the neurovascular unit: from clinical data to experimental evidence. J Cereb Blood Flow Metab 2011; 31 (11): 2119–34. Doi: 10.1038/jcbfm.2011.127.
7. Broussalis E, Trinka E, Killer M et al. Current therapies in ischemic stroke. Part B. Future candidates in stroke therapy and experimental studies. Drug Discov Today 2012; 17 (13–14): 671–84. Doi: 10.1016/j.drudis.2012.02.011.
8. O'Collins VE, Macleod MR, Donnan GA, Howells DW. Evaluation of combination therapy in animal models of cerebral ischemia. J Cereb Blood Flow Metab 2012; 32 (4): 585–97. Doi: 10.1038/jcbfm.2011.203.
9. Wang Y, Zhang ZG, Rhodes K et al. Post-ischemic treatment with erythropoietin or carbamylated erythropoietin reduces infarction and improves neurological outcome in a rat model of focal cerebral ischemia. Br J Pharmacol 2007; 151 (8): 1377–84.
10. Solaroglu I, Cahill J, Tsubokawa T et al. Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation. Neurol Res 2009; 31 (2): 167–72. Doi: 10.1179/174313209X393582.
11. Yang J, Guo L, Liu R, Liu H. Neuroprotective effects of VEGF administration after focal cerebral ischemia/reperfusion: dose response and time window. Neurochem Int 2012; 60 (6): 592–6. Doi: 10.1016/j.neuint.2012.02.020.
12. Белова Ю.А., Чуксина Ю.Ю., Шевелев С.В. и др. Уровень эндотелиальных прогениторных клеток у больных с ишемическим инсультом и эффективность реабилитации. Альманах клин. медицины. 2015; 39: 45–50. / Belova Iu.A., Chuksina Iu.Iu., Shevelev S.V. i dr. Uroven' endotelial'nykh progenitornykh kletok u bol'nykh s ishemicheskim insul'tom i effektivnost' reabilitatsii. Al'manakh klin. meditsiny. 2015; 39: 45–50. [in Russian]
13. Masliah E, Diez-Tejedor E. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders. Drugs Today 2012; 48 (Suppl. A): 3–24. Doi: 10.1358/dot.2012.48 (Suppl. A).1739716.
14. Zhang L, Chopp M, Meier DH et al. Sonic hedgehog signaling pathway mediates cerebrolysin-improved neurological function after stroke. Stroke 2013; 44: 1965–72. Doi: 10.1161/ STROKEAHA.111.000831.
15. Felling RJ, Song H. Epigenetic mechanisms of neuroplasticity and the implications for stroke recovery. Exp Neurol 2015; 268: 37–45. Doi: 10.1016/j.expneurol.2014.09.017.
16. Heiss WD, Brainin M, Bornstein NM et al. Cerebrolysin Acute Stroke Treatment in Asia (CASTA) Investigators. Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Stroke 2012; 43 (3): 630–6. Doi: 10.1161/STROKEAHA.111.628537.
17. Lang W, Stadler CH, Poljakovic Z, Fleet D. Lyse Study Group. A prospective, randomized, placebo-controlled, double-blind trial about safety and efficacy of combined treatment with alteplase (rt-PA) and Cerebrolysin in acute ischaemic hemispheric stroke. Int J Stroke 2013; 8 (2): 95–104. Doi: 10.1111/j.1747-4949.2012.00901.x.
18. Muresanu DF, Heiss WD, Hoemberg V et al. Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial. Stroke 2016; 47 (1): 151–9. Doi: 10.1161/STROKEAHA.115.009416.
19. Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res 1981; 4: 483–92. Doi: 10.1097/00004356-198112000-00001.
20. Garg R, Chaudhuri A, Munschauer F, Dandona P. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke 2006; 37 (1): 267–73.
21. Huang SS, Lu YJ, Huang JP et al. The essential role of endothelial nitric oxide synthase activation in insulin-mediated neuroprotection against ischemic stroke in diabetes. J Vasc Surg 2014; 59 (2): 483–91. Doi: 10.1016/j.jvs.2013.03.023.
22. Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Re 2012; 2012: 384017. Doi: 10.1155/2012/384017.
23. Lioutas VA, Novak V. Intranasal insulin neuroprotection in ischemic stroke. Neural Regen Res 2016; 11 (3): 400–1. Doi: 10.4103/1673-5374.179040.
24. Zhu H, Zhang Y, Shi Z et al. The Neuroprotection of Liraglutide Against Ischaemia-induced Apoptosis through the Activation of the PI3K/AKT and MAPK Pathways. Sci Rep 2016; 6: 26859. Doi: 10.1038/srep26859.
25. Campbell BC, Christensen S, Tress BM et al. EPITHET Investigators. Failure of collateral blood flow is associated with infarct growth in ischemic stroke. J Cereb Blood Flow Metab 2013; 33 (8): 1168–72. Doi: 10.1038/jcbfm.2013.77.
26. Shuaib A, Butcher K, Mohammad AA et al. Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target. Lancet Neurol 2011; 10 (10): 909–21. Doi: 10.1016/S1474-4422(11)70195-8.
27. Cuccione E, Padovano G, Versace A et al. Cerebral collateral circulation in experimental ischemic stroke. Exp Transl Stroke Med 2016; 8: 2. Doi: 10.1186/s13231-016-0015-0.eCollection 2016.
2. Espinosa de Rueda M, Parrilla G, Manzano-Fernández S et al. Combined multimodal computed tomography score correlates with futile recanalization after thrombectomy in patients with acute stroke. Stroke 2015; 46 (9): 2517–22. Doi: 10.1161/STROKEAHA.114.008598.
3. Gomis M, Dávalos A. Recanalization and reperfusion therapies of acute ischemic stroke: what have we learned, what are the major research questions, and wh ere are we headed? Front Neurol 2014; 5: 226. Doi: 10.3389/fneur.2014.00226. eCollection 2014.
4. Savitz SI, Fisher M. Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials. Ann Neurol 2007; 61 (5): 396–402.
5. Fisher M, Feuerstein G, Howells DW et al. STAIR Group. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009; 40 (6): 2244–50. Doi: 10.1161/STROKEAHA.108.541128.
6. Vivien D, Gauberti M, Montagne A et al. Impact of tissue plasminogen activator on the neurovascular unit: from clinical data to experimental evidence. J Cereb Blood Flow Metab 2011; 31 (11): 2119–34. Doi: 10.1038/jcbfm.2011.127.
7. Broussalis E, Trinka E, Killer M et al. Current therapies in ischemic stroke. Part B. Future candidates in stroke therapy and experimental studies. Drug Discov Today 2012; 17 (13–14): 671–84. Doi: 10.1016/j.drudis.2012.02.011.
8. O'Collins VE, Macleod MR, Donnan GA, Howells DW. Evaluation of combination therapy in animal models of cerebral ischemia. J Cereb Blood Flow Metab 2012; 32 (4): 585–97. Doi: 10.1038/jcbfm.2011.203.
9. Wang Y, Zhang ZG, Rhodes K et al. Post-ischemic treatment with erythropoietin or carbamylated erythropoietin reduces infarction and improves neurological outcome in a rat model of focal cerebral ischemia. Br J Pharmacol 2007; 151 (8): 1377–84.
10. Solaroglu I, Cahill J, Tsubokawa T et al. Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation. Neurol Res 2009; 31 (2): 167–72. Doi: 10.1179/174313209X393582.
11. Yang J, Guo L, Liu R, Liu H. Neuroprotective effects of VEGF administration after focal cerebral ischemia/reperfusion: dose response and time window. Neurochem Int 2012; 60 (6): 592–6. Doi: 10.1016/j.neuint.2012.02.020.
12. Белова Ю.А., Чуксина Ю.Ю., Шевелев С.В. и др. Уровень эндотелиальных прогениторных клеток у больных с ишемическим инсультом и эффективность реабилитации. Альманах клин. медицины. 2015; 39: 45–50. / Belova Iu.A., Chuksina Iu.Iu., Shevelev S.V. i dr. Uroven' endotelial'nykh progenitornykh kletok u bol'nykh s ishemicheskim insul'tom i effektivnost' reabilitatsii. Al'manakh klin. meditsiny. 2015; 39: 45–50. [in Russian]
13. Masliah E, Diez-Tejedor E. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders. Drugs Today 2012; 48 (Suppl. A): 3–24. Doi: 10.1358/dot.2012.48 (Suppl. A).1739716.
14. Zhang L, Chopp M, Meier DH et al. Sonic hedgehog signaling pathway mediates cerebrolysin-improved neurological function after stroke. Stroke 2013; 44: 1965–72. Doi: 10.1161/ STROKEAHA.111.000831.
15. Felling RJ, Song H. Epigenetic mechanisms of neuroplasticity and the implications for stroke recovery. Exp Neurol 2015; 268: 37–45. Doi: 10.1016/j.expneurol.2014.09.017.
16. Heiss WD, Brainin M, Bornstein NM et al. Cerebrolysin Acute Stroke Treatment in Asia (CASTA) Investigators. Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Stroke 2012; 43 (3): 630–6. Doi: 10.1161/STROKEAHA.111.628537.
17. Lang W, Stadler CH, Poljakovic Z, Fleet D. Lyse Study Group. A prospective, randomized, placebo-controlled, double-blind trial about safety and efficacy of combined treatment with alteplase (rt-PA) and Cerebrolysin in acute ischaemic hemispheric stroke. Int J Stroke 2013; 8 (2): 95–104. Doi: 10.1111/j.1747-4949.2012.00901.x.
18. Muresanu DF, Heiss WD, Hoemberg V et al. Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial. Stroke 2016; 47 (1): 151–9. Doi: 10.1161/STROKEAHA.115.009416.
19. Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res 1981; 4: 483–92. Doi: 10.1097/00004356-198112000-00001.
20. Garg R, Chaudhuri A, Munschauer F, Dandona P. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke 2006; 37 (1): 267–73.
21. Huang SS, Lu YJ, Huang JP et al. The essential role of endothelial nitric oxide synthase activation in insulin-mediated neuroprotection against ischemic stroke in diabetes. J Vasc Surg 2014; 59 (2): 483–91. Doi: 10.1016/j.jvs.2013.03.023.
22. Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Re 2012; 2012: 384017. Doi: 10.1155/2012/384017.
23. Lioutas VA, Novak V. Intranasal insulin neuroprotection in ischemic stroke. Neural Regen Res 2016; 11 (3): 400–1. Doi: 10.4103/1673-5374.179040.
24. Zhu H, Zhang Y, Shi Z et al. The Neuroprotection of Liraglutide Against Ischaemia-induced Apoptosis through the Activation of the PI3K/AKT and MAPK Pathways. Sci Rep 2016; 6: 26859. Doi: 10.1038/srep26859.
25. Campbell BC, Christensen S, Tress BM et al. EPITHET Investigators. Failure of collateral blood flow is associated with infarct growth in ischemic stroke. J Cereb Blood Flow Metab 2013; 33 (8): 1168–72. Doi: 10.1038/jcbfm.2013.77.
26. Shuaib A, Butcher K, Mohammad AA et al. Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target. Lancet Neurol 2011; 10 (10): 909–21. Doi: 10.1016/S1474-4422(11)70195-8.
27. Cuccione E, Padovano G, Versace A et al. Cerebral collateral circulation in experimental ischemic stroke. Exp Transl Stroke Med 2016; 8: 2. Doi: 10.1186/s13231-016-0015-0.eCollection 2016.
________________________________________________
1. Powers WJ, Derdeyn CP, Biller J et al. American Heart Association Stroke Council. 2015 AHA/ASA focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals fr om the American heart association/American stroke association. Stroke 2015; 46 (10): 3020–35. Doi:10.1161/STR.0000000000000074.
2. Espinosa de Rueda M, Parrilla G, Manzano-Fernández S et al. Combined multimodal computed tomography score correlates with futile recanalization after thrombectomy in patients with acute stroke. Stroke 2015; 46 (9): 2517–22. Doi: 10.1161/STROKEAHA.114.008598.
3. Gomis M, Dávalos A. Recanalization and reperfusion therapies of acute ischemic stroke: what have we learned, what are the major research questions, and wh ere are we headed? Front Neurol 2014; 5: 226. Doi: 10.3389/fneur.2014.00226. eCollection 2014.
4. Savitz SI, Fisher M. Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials. Ann Neurol 2007; 61 (5): 396–402.
5. Fisher M, Feuerstein G, Howells DW et al. STAIR Group. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009; 40 (6): 2244–50. Doi: 10.1161/STROKEAHA.108.541128.
6. Vivien D, Gauberti M, Montagne A et al. Impact of tissue plasminogen activator on the neurovascular unit: from clinical data to experimental evidence. J Cereb Blood Flow Metab 2011; 31 (11): 2119–34. Doi: 10.1038/jcbfm.2011.127.
7. Broussalis E, Trinka E, Killer M et al. Current therapies in ischemic stroke. Part B. Future candidates in stroke therapy and experimental studies. Drug Discov Today 2012; 17 (13–14): 671–84. Doi: 10.1016/j.drudis.2012.02.011.
8. O'Collins VE, Macleod MR, Donnan GA, Howells DW. Evaluation of combination therapy in animal models of cerebral ischemia. J Cereb Blood Flow Metab 2012; 32 (4): 585–97. Doi: 10.1038/jcbfm.2011.203.
9. Wang Y, Zhang ZG, Rhodes K et al. Post-ischemic treatment with erythropoietin or carbamylated erythropoietin reduces infarction and improves neurological outcome in a rat model of focal cerebral ischemia. Br J Pharmacol 2007; 151 (8): 1377–84.
10. Solaroglu I, Cahill J, Tsubokawa T et al. Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation. Neurol Res 2009; 31 (2): 167–72. Doi: 10.1179/174313209X393582.
11. Yang J, Guo L, Liu R, Liu H. Neuroprotective effects of VEGF administration after focal cerebral ischemia/reperfusion: dose response and time window. Neurochem Int 2012; 60 (6): 592–6. Doi: 10.1016/j.neuint.2012.02.020.
12. Belova Iu.A., Chuksina Iu.Iu., Shevelev S.V. i dr. Uroven' endotelial'nykh progenitornykh kletok u bol'nykh s ishemicheskim insul'tom i effektivnost' reabilitatsii. Al'manakh klin. meditsiny. 2015; 39: 45–50. [in Russian]
13. Masliah E, Diez-Tejedor E. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders. Drugs Today 2012; 48 (Suppl. A): 3–24. Doi: 10.1358/dot.2012.48 (Suppl. A).1739716.
14. Zhang L, Chopp M, Meier DH et al. Sonic hedgehog signaling pathway mediates cerebrolysin-improved neurological function after stroke. Stroke 2013; 44: 1965–72. Doi: 10.1161/ STROKEAHA.111.000831.
15. Felling RJ, Song H. Epigenetic mechanisms of neuroplasticity and the implications for stroke recovery. Exp Neurol 2015; 268: 37–45. Doi: 10.1016/j.expneurol.2014.09.017.
16. Heiss WD, Brainin M, Bornstein NM et al. Cerebrolysin Acute Stroke Treatment in Asia (CASTA) Investigators. Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Stroke 2012; 43 (3): 630–6. Doi: 10.1161/STROKEAHA.111.628537.
17. Lang W, Stadler CH, Poljakovic Z, Fleet D. Lyse Study Group. A prospective, randomized, placebo-controlled, double-blind trial about safety and efficacy of combined treatment with alteplase (rt-PA) and Cerebrolysin in acute ischaemic hemispheric stroke. Int J Stroke 2013; 8 (2): 95–104. Doi: 10.1111/j.1747-4949.2012.00901.x.
18. Muresanu DF, Heiss WD, Hoemberg V et al. Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial. Stroke 2016; 47 (1): 151–9. Doi: 10.1161/STROKEAHA.115.009416.
19. Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res 1981; 4: 483–92. Doi: 10.1097/00004356-198112000-00001.
20. Garg R, Chaudhuri A, Munschauer F, Dandona P. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke 2006; 37 (1): 267–73.
21. Huang SS, Lu YJ, Huang JP et al. The essential role of endothelial nitric oxide synthase activation in insulin-mediated neuroprotection against ischemic stroke in diabetes. J Vasc Surg 2014; 59 (2): 483–91. Doi: 10.1016/j.jvs.2013.03.023.
22. Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Re 2012; 2012: 384017. Doi: 10.1155/2012/384017.
23. Lioutas VA, Novak V. Intranasal insulin neuroprotection in ischemic stroke. Neural Regen Res 2016; 11 (3): 400–1. Doi: 10.4103/1673-5374.179040.
24. Zhu H, Zhang Y, Shi Z et al. The Neuroprotection of Liraglutide Against Ischaemia-induced Apoptosis through the Activation of the PI3K/AKT and MAPK Pathways. Sci Rep 2016; 6: 26859. Doi: 10.1038/srep26859.
25. Campbell BC, Christensen S, Tress BM et al. EPITHET Investigators. Failure of collateral blood flow is associated with infarct growth in ischemic stroke. J Cereb Blood Flow Metab 2013; 33 (8): 1168–72. Doi: 10.1038/jcbfm.2013.77.
26. Shuaib A, Butcher K, Mohammad AA et al. Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target. Lancet Neurol 2011; 10 (10): 909–21. Doi: 10.1016/S1474-4422(11)70195-8.
27. Cuccione E, Padovano G, Versace A et al. Cerebral collateral circulation in experimental ischemic stroke. Exp Transl Stroke Med 2016; 8: 2. Doi: 10.1186/s13231-016-0015-0.eCollection 2016.
Авторы
С.В.Котов*, Е.В.Исакова, О.П.Сидорова, Ю.А.Белова
ГБУЗ МО Московский областной научно-исследовательский клинический институт им. М.Ф.Владимирского. 129110, Россия, Москва, ул. Щепкина, д. 61/2
*kotovsv@yandex.ru
ГБУЗ МО Московский областной научно-исследовательский клинический институт им. М.Ф.Владимирского. 129110, Россия, Москва, ул. Щепкина, д. 61/2
*kotovsv@yandex.ru
________________________________________________
S.V.Kotov*, E.V.Isakova, O.P.Sidorova, Yu.A.Belova
M.F.Vladimirskiy Moscow regional research clinical institute. 129110, Russian Federation, Moscow, ul. Shchepkina, d. 61/2
*kotovsv@yandex.ru
M.F.Vladimirskiy Moscow regional research clinical institute. 129110, Russian Federation, Moscow, ul. Shchepkina, d. 61/2
*kotovsv@yandex.ru
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