Methods of modeling and morphofunctional markers of cerebral ischemia
Abstract
In the structure of morbidity and mortality worldwide, the leading positions are occupied by cerebrovascular diseases, the leading among which are ischemic brain damage. Cerebral ischemia is a severe neurodegenerative condition that, depending on the affected area, can interfere with the realization of cognitive and motor functions of the central nervous system. Even short-term cerebral ischemia leads to its deep damage. The key links in the pathogenesis of cerebral ischemia are the lack of oxygenation of neurons, inhibition of aerobic activity in the brain and activation of the anaerobic pathway for glucose utilization, decreased energy production, disruption of transport of potential-determining ions, changes in the acid-base state, excitotoxicity, activation of the inflammatory process, oxidative and nitrosative stress, apoptosis. These processes cannot be modeled in vitro, and most of the studies of brain pathology of ischemic genesis are carried out on animals. Adequate models of cerebral ischemia contribute to detailing their pathogenesis and allow us to study the dynamics of adaptive mechanisms, which serves as a fundamental basis for improving the diagnosis, treatment and prevention of this pathology. The literature presents a variety of methods that allow the simulation of cerebral ischemia of varying degrees and different pathogenetic variants. Complete (total) cerebral ischemia is achieved by decapitation, cardiac arrest or occlusion of the aorta or hollow vein, incomplete (subtotal) ischemia - by occlusion of both common carotid arteries against intracranial hypertension, partial ischemia - by occlusion of the common carotid artery, focal ischemia - by occlusion of the middle cerebral artery or its embolism by macrospheres, multifocal cerebral ischemia - by multiple embolism microspheres. This review is devoted to the analysis and systematization of literature data on the modeling of cerebral ischemia and the description of structural and metabolic disorders of the neocortex and hippocampus neurons. The degree of expression of these changes act as markers of the depth of hypoxic damage and the effectiveness of the methods used to correct them.
About the Authors
E. I. Bon`
УО «Гродненский государственный медицинский университет»
Russian Federation
Russian Federation
N. E. Maksimovich
УО «Гродненский государственный медицинский университет»
Russian Federation
Russian Federation
References
1. Богатырева М.Д., Клочихина О.А., Стаховская Л.В. Эпидемиология инсульта в Ставропольском крае // Медицинский вестник Северного Кавказа. - 2013. - Т. 8. - № 1. - С. 34-38.
2. Гончар И.А., Степанова Ю.И., Прудывус И.С. Биохимические предикторы и маркеры инфаркта головного мозга / под ред. д.м.н., проф. В.С. Камышникова. - Минск: БелМАПО, 2013. 512 с.
3. Максимович Н.Е. Современные представления о механизмах развития ишемических повреждений головного мозга и путях коррекции этой патологии // Актуальные теоретические и прикладные аспекты патофизиологии: мат-лы Республиканской научно-практ. конф. с межд. участием. - Гродно, 2010. - С. 149-157.
4. Мартынова О.В., Тверской А.В., Покровский М.В., Мартынов М.А., Шкилева И.Ю., Шелякина Е.В., Анциферов О.В., Мухина Т.С. Морфологические изменения нейронов головного мозга крыс при двух-, четырёхсосудистой моделях ишемического повреждения головного мозга крыс и их коррекция тадалафилом в эксперименте // Современные проблемы науки и образования. - 2016. - № 6. - C. 56-61.
5. Молекулярная нейроморфология. Нейродегенерация и оценка реакции нервных клеток на повреждение / под ред. Д.Э. Коржевского. - СПб: СпецЛит, 2015. - 110 с.
6. Попова Э.Н. Ультраструктура мозга, алкоголь и потомство. - М.: Научный мир, 2010, 155 с.
7. Розвадовский В.Д., Тренин С.О., Тельпухов В.И. Микрохирургическая модель ишемии головного мозга // Журнал патологической физиологии и общей патологии. - 1985. - № 2. - С. 87-92.
8. Рукан Т.А., Максимович Н.Е., Зиматкин С.М. Активность некоторых ферментов в нейронах фронтальной коры головного мозга в ранний постишемический период // Вестник ВГМУ. - 2013. - № 2. - С. 50-54.
9. Рукан Т.А., Максимович Н.Е., Зиматкин С.М. Морфофункциональные изменения нейронов фронтальной коры головного мозга в условиях его ишемии-реперфузии // Журнал Гродненского государственного медицинского университета. - 2012. - № 4. - С. 35-38.
10. Трушель Н.А. Сравнительная характеристика строения сосудов виллизиева круга головного мозга у человека и лабораторных животных // Военная медицина. - 2009. - № 2. - С. 47-51.
11. Щербак Н.С., Галагудза М.М., Кузьменков А.Н. Новый способ моделирования обратимой глобальной ишемии головного мозга // Бюлл. экcп. биол. и мед. - 2011. - Т. 152, № 11. - С. 592-595.
12. Beech J., et al. Further characterisation of a thromboembolic model of stroke in the rat // Brain Res. - 2016. - V. 895. - Pp. 18-24.
13. Carmichael S.T. Rodent models of focal stroke: size, mechanism, and purpose // Neuro. - 2005. - V. 2. - Pp. 396-409.
14. Chu L., Sharma M., Shoamanesh A. Severe cerebral vasospasm and infarction after minor head trauma // Can. J. Neurol. Sci. - 2017. - V. 44. - Pp. 618-620.
15. Clark I., et al. The regulation of matrix metalloproteinases and their inhibitors // Int. J. Biochem. Cell Biol. - 2008. - Vol. 40. - No. 6-7.
16. Dave K., et al. Ischemic preconditioning preserves mitochondrial function after global cerebral ischemia in rat hippocampus // J. Cereb. Blood Flow. Metab. - 2001. - Vol. 21(12). - Рp. 1401-1410.
17. Dittmar M.S., et al. Fischer-344 rats are unsuitable for the MCAO filament model due to their cerebrovascular anatomy // J. Neurosci. Methods. - 2006. - V. 14. - Pp. 78-85.
18. Gallyas F., et al. Supravital microwave experiments support that the formation of "dark" neurons is propelled by phase transition in an intracellular gel system // Brain Res. - 2009. - Vol. 1270. - Pp. 152-156.
19. Gill R., Foster A., Woodruff G. Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil // Neurosci. - 1987. - V. 7. - Pp. 3343-3349.
20. Graham S.M., McCullough L.D., Murphy S.J. Animal Models of Ischemic Stroke: Balancing Experimental Aims and Animal Care // Comp. Med. - 2004. - V. 54. - Pp. 486-496.
21. Hao C., et al. Effect of human recombinant prourokinase (rhpro-UK) on thromboembolic stroke in rats // Eur. J. Pharmacol. - 2017. - V. 56. - Pp. 89-101.
22. Hossmann K.-A. Experimental models for the investigation of brain ischemia // Cardiovascular Research. - 1998. - V. 39. - Pp. 106-120.
23. Kcjita Y., et al. Possible role of nitric oxide in autoregulalory response in rat ihtracerebral arterioles // Neurosurgery. - 1998. - V. 42. - Pp. 834-842.
24. Marnane M., Duggan C.A., Sheehan O.C., et al. Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-S-C-O, and causative classification system: direct comparison in the North Dublin Population Stroke Study // Stroke. - 2010. - V. 41. - Pp. 1579-1586.
25. Mayzel-Oreg O., et al. Microsphere-induced embolic stroke: an MRI study // Magn. Reson Med. - 2015. - V. 51. - Pp. 1232-1238.
26. McGraw C.P. Experimental cerebral infarction: effects of pentobarbital in Mongolian gerbils // Arch. Neurol. - 1977. - Vol. 34. - Pp. 334-336.
27. Pulsinelli W.A., Brierley J.B. A new model of bilateral hemispheric ischemia in the unanesthetized rat // Stroke. - 1979. - V. 10. - Pp. 267-272.
28. Ryosuke M.D., et al. Effect of danttrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia // Anesthesiology. - 2002. - Vol. 96. - Pp. 705-710.
29. Sacco S.E., Whisnant J.P., Broderick J.P. Epidemiological characteristics of lacunar infarcts in a population // Stroke. - 1991. - V. 22 - Pp. 1236-1241.
30. Smrcka M., Ogilvy C., Koroshetz W. Small aneurysms as a cause of thromboembolic stroke // Bratisl Lek Listy. - 2002. - V. 103(8). - Pp. 250-253.
31. Tamura A., et al. Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion // J. Cereb. Blood Flow Metab. - 1981. - V. 1. - Pp. 53-60.
32. Vaupel P., Mayer A. Hypoxia in cancer: significance and impact on clinical outcome // Cancer Metastasis Reviews. - 2007. - Vol. 26. - Pp. 225-239.
33. Weigand M., et al. Neuronspecific enolase as a marker of fatal outcome in patients with severe sepsis and septic shock // Anesthesiology. - 2000. - Vol. 92. - Pp. 905-907.
34. White B.C., et al. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury // J. Neurol. Sci. - 2000. - Vol. 179. - No. 1-2. - Pp. 1-33.
35. Yamaguchi M., et al. One-stage anterior approach for four-vessel occlusion in rat // Stroke. - 2005. - V. 36. - Pp. 2212-2214.
36. Bogatyreva M.D., Klochikhina O.A., Stakhovskaya L.V. Epidemiologiya insul'ta v Stavropol'skom kraye [Stork epidemiology in Stavropol Krai]. Meditsinskiy vestnik Severnogo Kavkaza [The medical bulletin of the North Caucasus]. 2013. T. 8. No. 1. Pp. 34-38. (In Russian).
37. Gonchar I.A., Stepanova J.I., Prudyvus I.S. Biokhimicheskiye prediktory i markery infarkta golovnogo mozga [Biochemical predictors and markers of ischemic stroke] / Ed. by Prof. V.S. Kamyshnikov. Minsk, Belarusian Medical Academy of Postgraduate Education, 2013. 512 p. (In Russian).
38. Maksimovich N.Ye. Sovremennyye predstavleniya o mekhanizmakh razvitiya ishemicheskikh povrezhdeniy golovnogo mozga i putyakh korrektsii etoy patologii [Modern ideas about the mechanisms of development of ischemic brain damage and ways of correction of this pathology]. Aktual'nyye teoreticheskiye i prikladnyye aspekty patofiziologii: mat-ly Respublikanskoy nauchno-prakt. konf. s mezhd. uchastiyem [Actual theoretical and applied aspects of pathophysiology: materials of the Republican scientific and practical conference with international participation]. Grodno. 2010. Pp. 149-157. (In Russian).
39. Martynova O.V., Tverskoi A.V., Pokrovsky M.V., Martynov M.A., Shkileva I.Yu., Shelyakina E.V., Antsiferov O.V., Mukhina Т.S. Morfologicheskiye izmeneniya neyronov golovnogo mozga krys pri dvukh-, chetyrokhsosudistoy modelyakh ishemicheskogo povrezhdeniya golovnogo mozga krys i ikh korrektsiya tadalafilom v eksperimente [Morphological changes in brain neurons of rats with two-, four-cavity models of ischemic damage to the brain of rats and their correction by tadalafil in the experiment]. Sovremennye problemy nauki i obrazovaniya [Modern problems of science and education]. 2016. No. 6. Pp. 56-61. (In Russian).
40. Molekulyarnaya neyromorfologiya. Neyrodegeneratsiya i otsenka reaktsii nervnykh kletok na povrezhdeniye [Molecular neuromorphology. Neurodegeneration and evaluation of the reaction of nerve cells to damage]. Ed. by Korzhevsky D.E. St. Petersburg. : SpetsLit, 2015. 110 p. (In Russian).
41. Popova E.N. Ul'trastruktura mozga, alkogol' i potomstvo [Ultrastructure of the brain, alcohol and offspring]. Moscow: Nauchnyj mir, 2010, 155 p. (In Russian).
42. Rozvadovskiy V.D., Trenin S.O., Tel'pukhov V.I. Mikrokhirurgicheskaya model' ishemii golovnogo mozga [Microsurgical model of cerebral ischemia]. Zhurnal patologicheskoy fiziologii i obshchey patologii [Journal of Pathological physiology and general pathology]. 1985. No. 2. Pp. 87-92. (In Russian).
43. Rukan T.A., Maksimovich N.E., Zimatkin S.M. Aktivnost' nekotorykh fermentov v neyronakh frontal'noy kory golovnogo mozga v ranniy postishemicheskiy period [Activity of some enzymes in the neurons of the frontal cortex of the brain in the early postischemic period]. Vestnik VGMU [Bulletin of the Voronezh State Medical University]. 2013. No. 2. Pp. 50-54. (In Russian).
44. Rukan T.A., Maksimovich N.E., Zimatkin S.M. Morfofunktsional'nyye izmeneniya neyronov frontal'noy kory golovnogo mozga v usloviyakh yego ishemii-reperfuzi [Morphofunctional changes in the neurons of the frontal cortex of the brain under conditions of its ischemia-reperfusion]. Zhurnal Grodnenskogo gosudarstvennogo medicinskogo universiteta [Journal of the Grodno State Medical University]. 2012. No. 4. Pp. 35-38. (In Russian).
45. Trushel' N.A. Sravnitel'naya kharakteristika stroyeniya sosudov villiziyeva kruga golovnogo mozga u cheloveka i laboratornykh zhivotnykh [Comparative characteristics of the structure of vessels of the Willis circle of the brain in humans and laboratory animals]. Voyennaya meditsina [Military medicine]. 2009. No. 2. Pp. 47-51. (In Russian).
46. Shcherbak N.S., Galagudza M.M., Kuz'menkov A.N. Novyy sposob modelirovaniya obratimoy global'noy ishemii golovnogo mozga [A new way to model reversible global brain ischemia]. Byull. eksp. biol. i med. [Bulletin of Experimental Biology and Medicine]. 2011. Vol. 152, No. 11. Pp. 592-595. (In Russian)
47. Beech J., et al. Further characterisation of a thromboembolic model of stroke in the rat. Brain Res. 2016. V. 895. Pp. 18-24.
48. Carmichael S.T. Rodent models of focal stroke: size, mechanism, and purpose. Neuro. 2005. V. 2. Pp. 396-409.
49. Chu L., Sharma M., Shoamanesh A. Severe cerebral vasospasm and infarction after minor head trauma. Can. J. Neurol. Sci. 2017. V. 44. Pp. 618-620.
50. Clark I., et al. The regulation of matrix metalloproteinases and their inhibitors. Int. J. Biochem. Cell Biol. 2008. Vol. 40. No. 6-7.
51. Dave K., et al. Ischemic preconditioning preserves mitochondrial function after global cerebral ischemia in rat hippocampus. J. Cereb. Blood Flow. Metab. 2001. Vol. 21(12). Рp. 1401-1410.
52. Dittmar M.S., et al. Fischer-344 rats are unsuitable for the MCAO filament model due to their cerebrovascular anatomy. J. Neurosci. Methods. 2006. V. 14. Pp. 78-85.
53. Gallyas F., et al. Supravital microwave experiments support that the formation of "dark" neurons is propelled by phase transition in an intracellular gel system. Brain Res. 2009. Vol. 1270. Pp. 152-156.
54. Gill R., Foster A., Woodruff G. Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. Neurosci. 1987. V. 7. Pp. 3343-3349.
55. Graham S.M., McCullough L.D., Murphy S.J. Animal Models of Ischemic Stroke: Balancing Experimental Aims and Animal Care. Comp. Med. 2004. V. 54. Pp. 486-496.
56. Hao C., et al. Effect of human recombinant prourokinase (rhpro-UK) on thromboembolic stroke in rats. Eur. J. Pharmacol. 2017. V. 56. Pp. 89-101.
57. Hossmann K.-A. Experimental models for the investigation of brain ischemia. Cardiovascular Research. 1998. V. 39. Pp. 106-120.
58. Kcjita Y., et al. Possible role of nitric oxide in autoregulalory response in rat ihtracerebral arterioles. Neurosurgery. 1998. V. 42. Pp. 834-842.
59. Marnane M., Duggan C.A., Sheehan O.C., et al. Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-S-C-O, and causative classification system: direct comparison in the North Dublin Population Stroke Study. Stroke. 2010. V. 41. Pp. 1579-1586.
60. Mayzel-Oreg O., et al. Microsphere-induced embolic stroke: an MRI study. Magn. Reson Med. 2015. V. 51. Pp. 1232-1238.
61. McGraw C.P. Experimental cerebral infarction: effects of pentobarbital in Mongolian gerbils. Arch. Neurol. 1977. Vol. 34. Pp. 334-336.
62. Pulsinelli W.A., Brierley J.B. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke. 1979. V. 10. Pp. 267-272.
63. Ryosuke M.D., et al. Effect of danttrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia. Anesthesiology. 2002. Vol. 96. Pp. 705-710.
64. Sacco S.E., Whisnant J.P., Broderick J.P. Epidemiological characteristics of lacunar infarcts in a population. Stroke. 1991. V. 22 Pp. 1236-1241.
65. Smrcka M., Ogilvy C., Koroshetz W. Small aneurysms as a cause of thromboembolic stroke. Bratisl Lek Listy. 2002. V. 103(8). Pp. 250-253.
66. Tamura A., et al. Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J. Cereb. Blood Flow Metab. 1981. V. 1. Pp. 53-60.
67. Vaupel P., Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Reviews. 2007. Vol. 26. Pp. 225-239.
68. Weigand M., et al. Neuronspecific enolase as a marker of fatal outcome in patients with severe sepsis and septic shock. Anesthesiology. 2000. Vol. 92. Pp. 905-907.
69. White B.C., et al. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J. Neurol. Sci. 2000. Vol. 179. No. 1-2. Pp. 1-33.
70. Yamaguchi M., et al. One-stage anterior approach for four-vessel occlusion in rat. Stroke. 2005. V. 36. Pp. 2212-2214.
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Bon` E.I., Maksimovich N.E. Methods of modeling and morphofunctional markers of cerebral ischemia. Journal Biomed. 2018;(2):59-71. (In Russ.)
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