INFLUENCE OF ISCHEMIC POSTCONDITIONING ON BCL-2 PROTEIN EXPRESSION OF NEOCORTEX NEURONS IN GLOBAL CEREBRAL ISCHEMIA-REPERFUSION

We investigated the Bcl-2 protein expression in neurons of layers II, III, and V of the cerebral cortex of rats at an early and lasting reperfusion period after a 10-minute complete global cerebral ischemia and after application of ischemic postconditioning (IPostC). Reversible global brain ischemia leads to a shortage of morphologically unaltered neurons in layers II and III of the cortex in which increases in the late reperfusion period and is accompanied by a decrease in the level Bcl-2 protein expression in the cytoplasm of neurons unchanged. IPostC, applied as three episodes of ischemia-reperfusion lasting 15/15 seconds contributed to significant increase in the number of morphologically unchanged neurons in layers II, III, and V of the cortex and to an increase Bcl- 2 protein expression in cytoplasm of morphologically unchanged neurons of these layers. In the layer of in the early reperfusion period, there were no changes in the number of morphologically unchanged neurons, but they found a decrease in the level of Bcl-2 protein expression, which increased after application of IPostC. The obtained results allow to conclude, that the implementation of the neuroprotective effect of IPostC for layers II, III, and V of the cortex during global ischemia-reperfusion brain in rats, is implemented through a mechanism leading to increased Bcl-2 protein expression.

неокортекс, Bcl-2, ишемия-реперфузия, ишемическое посткондиционирование, крысы, neocortex, Bcl-2, ischemia-reperfusion, ischemic postconditioning, rats

1. Постановление Главного государственного санитарного врача Российской Федерации от 29.08.2014 № 51 «Санитарно-эпидемиологические требования к устройству, оборудованию и содержанию экспериментальнобиологических клиник (вивариев)». Зарегистрировано в Минюсте России 31 октября 2014 г. № 34547

2. Ветровой О.В., Рыбникова Е.А., Глущенко Т.С., Самойлов М.О. Влияние гипоксического посткондиционирования на экспрессию противоапоптотического белка Bcl-2 и нейротрофина BNDF в поле СА1 гиппокампа крыс, переживших тяжелую гипоксию. Морфология. 2014; 145. №2. С. 16-20

3. Ding Z.M, Wu B, Zhang W.Q, et al. Neuroprotective Effects of Ischemic Preconditioning and Postconditioning on Global Brain Ischemia in Rats through the Same Effect on Inhibition of Apoptosis. Int J Mol Sci. 2012; 13(5): 60896101.

4. Nemethova M, Danielisova V, Gottlieb M, et al. Ischemic postconditioning in the rat hippocampus: mapping of proteins involved in reversal of delayed neuronal death. Arch Ital Biol. 2010; 148(1): 23-32.

5. Щербак Н.С., Русакова А.Г., Галагудза М.М., Юкина Г.Ю., Баранцевич Е.Р., Томсон В.В., Шляхто Е.В. Изменение экспрессии белка Bcl2 в нейронах полей гиппокампа после применения ишемического посткондиционирования головного мозга. Морфология. 2015; 48(5): 21-27

6. Shcherbak N.S, Galagudza M.M, Kuzmenkov A.N, et al. A new rat model of reversible global cerebral ischemia. Bull Exp Biol Med. 2012; 152: 656-658

7. Щербак Н.С., Овчинников Д.А., Кузьменков А.Н., Галагудза М.М., Митрофанова Л.Б., Баранцевич Е.Р., Шляхто Е.В. Способ моделирования глобальной ишемии головного мозга у мелких лабораторных животных. Патент на изобретение 2464645 25.11.2010. Россия МПК G 09 B 23 28, A 61 B 17 00. - 2010148215/14

8. Щербак Н.С., Кузьменков А.Н., Овчинников Д.А., Галагудза М.М. Интубационная трубка для проведения искусственной вентиляции легких у грызунов. Патент на полезную модель 121389 27.04.12. Россия МПК G 09 B 23 28. - 2012117849/14

9. Paxinos G, Watson Ch. The rat brain in stereotaxic coordinates. N.Y. Academic Press. 1998.

10. Stummer W, Weber K, Tranmer B, et al. Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia. Stroke. 1994; 25: 1862-1869.

11. Linnik M, Miller J, Sprinkle-Cavallo J, et al. Apoptotic DNA fragmentation in the rat cerebral cortex induced by permanent middle cerebral artery occlusion. Brain. Res Mol Brain Res. 1995; 32: 116-124.

12. Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 1982; 239: 57-69.

13. Поташев Д.Д. Влияние шунтирования общих сонных артерий при острой окклюзии на цитоархитектонику неокортекса белых крыс. Морфология. 2006; 129(4): 102

14. Pulsinelli W.A, Buchan A.M. The four-vessel occlusion rat model: method for complete occlusion of vertebral arteries and control of collateral circulation. Stroke. 1988; 19: 913-914.

15. Kiessling M, Stumm G, Xie Y, et al. Differential transcription and translation of immediate early genes in the gerbil hippocampus after transient global ischemia. J Cereb Blood Flow Metab. 1993; 13: 914-924.

16. Xing B, Chen H, Zhang M, et al. Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat. Stroke. 2008; 39(8): 2362-2369.

17. Shimazaki K, Ishida A, Kawai N. Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the gerbil hippocampus. Neurosci Res. 1994; 20(1): 95-99.

18. Zhao H, Ren C, Chen X, Shen J. From rapid to delayed and remote postconditioning: the evolving concept of ischemic postconditioning in brain ischemia. Curr Drug Targets. 2012; 13: 173-187.

19. Merry D.E, Veis D.J, Hickey W.F, Korsmeyer S.J. Bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS. Development. 1994; 120; 2: 301-311.

20. Kane D.J, Ord T, Anton R, Bredesen D.E. Expression of bcl-2 inhibits necrotic neural cell death. J Neurosci Res. 1995; 40: 269-275.

21. Martinou J.C, Dubois-Dauphin M, Staple J.K, et al. Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron. 1994; 13(4): 1017-1030.

22. Cao Y.J, Shibata T, Rainov N.G. Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model. Gene Ther. 2002; 9(6): 415-419.