Changes in the Cellular Composition of the Cerebral Cortex in Rats with Different Levels of Cognitive Function in Cerebral Hypoperfusion Combined with Short-Term Physical Activity

The aim of the study was to detect the features of neurodystrophic changes in neurons and glia of the motor cortex of the brain in rats with different levels of cognitive functions and stress resistance with bilateral ligation of the common carotid arteries combined with short-term physical activity.

Material and methods. The study included 136 Wistar rats. All animals were divided into two subgroups depending on the results of testing in the Morris water maze: with a high and a low level of abilities for spatial environment learning. Animals of the experimental group were exposed to daily free swimming for 15 minutes, starting on the 7th and ending on the 35th days of the study. The rats were withdrawn from the experiment in 8, 14, 21, 35, 60, and 90 days after bilateral ligation of both carotid arteries. Histological sections of the precentral gyrus of the brain were stained according to Nissl and hematoxylin-eosin.

Results. On the 8th day of the experiment (1 day of short-term physical activity), the hemomicrocirculatory bed of the cerebral cortex was characterized by a decrease in venous hyperemia, and a decrease of tissue edema signs around the hemocapillaries, a characteristic feature of isolated cerebral hypoperfusion. Neurons with signs of hyperfunction and rod-shaped inclusions in the nuclei (Roncoronni bodies) were detected on the 14th, 21st, 28th days. Hemocapillaries formed compact groups of cells. Further, neurodystrophic changes were less pronounced in comparison with isolated cerebral hypoperfusion, this was accompanied by a decrease in venous hyperemia, preservation of perivasal cell groups up to the 60th day of the experiment. Roncoroni bodies disappeared on the 90th day of observation.

Conclusion. The effect of short-term physical activity on the development of cerebral hypoperfusion resulted in an increase in the number of neurons without irreversible changes, a decrease in neurodegenerative changes, and also reduced the severity of gliosis. The adaptive effect of short-term physical activity was more pronounced in animals with a high level of cognitive abilities, which was accompanied by a more significant decrease in the number of dead cells of the cerebral cortex. Day 28 was a critical point when gliosis and neuronal death were combined with the appearance of Roncoronni bodies and perikarion hypertrophy of some pyramidal neurons, as well as the concentration of gliocytes around hemocapillaries. The latter appears to be a sort of adaptation, since it is accompanied by a decrease in mortality in animals with a high level of cognitive abilities.

1. Vasil'ev YuG, Chuchkov VM. Neiro-glio-sosudistye otnosheniya v tsentral'noi nervnoi sisteme (morfologicheskoe issledovanie s elementami morfometricheskogo i matematicheskogo analiza). Izhevsk: ANK; 2003 (in Russian).

2. Grzybowski AM. Correlation analysis. Human Ecology. 2008;9 (in Russian).

3. Durov RA. Personnel potential of industrial development of Russia. Humanities and social Sciences. 2013;(3):2–8 (in Russian).

4. Zadnipryany IV, Sataieva TP. Application of antihypoxants in the correction of antenatal hypoxia based on its morphological and functional data. Crimea State Medical University named after S.I. Georgievskiy. 2013;1(1):13–21 (in Russian).

5. Ivlieva AL, Petritskaya EN, Rogatkin DA, Demin VA. Methodical features of the application of morris water maze for estimation of cognitive functions in animals. Russian journal of physiology. 2016;102(1):3–17 (in Russian).

6. Chrishtop VV, Nikonorova VG, Rumyantseva TА. Changes in the Cellular Composition of the Cerebral Cortex in Rats with Different Levels of Cognitive Functions Under Cerebral Hypoperfusion. Journal of Anatomy and Histopathology. 2019;8(4):22–9.doi.org/10.18499/2225-7357-2019-8-4-22-29 (in Russian).

7. Chrishtop VV, Pakhrova OA, Rumyantseva TA. Dynamics of permanent cerebral hypoxia of rats depending on individual features of higher nervous activity and sex. Medical News of North Caucasus. 2018;13(4):654–9. doi:10.14300/mnnc.2018.13129 (in Russian)

8. Monid MV, Droblenkov AV. Sosin DV., Shabanov PD. Reactive morphological changes of the rat brain anterior cingulate cortex after acute hypoxia. Vestnik Smolenskoy Gosudarstvennoy Medicinskoy Akademii. 2013;12(4):31–4] (in Russian).

9. Sergeev AV. Immunomorfologicheskaya i morfometricheskaya kharakteristika tormoznykh i vozbuzhdayushchikh neironov kory golovnogo mozga cheloveka v norme i pri khronicheskoi ishemii: avtoref. dis... kand. med. nauk. Novosibirsk; 2014 (in Russian).

10. Stepanov AS, Akulinin VA, Mysik AV, Stepanov SS, Avdeev DB. Neuro-Glio-Vascular Complexes of the Brain After Acute Ischemia. n General Reanimatology. 2017;13(6):6–17. doi:10.15360/1813-9779-2017-6-6-17 (in Russian).

11. Aytac E, Oktay Seymen H, Uzun H, Dikmen G, Altug T. Effects of iloprost on visual evoked potentials and brain tissue oxidative stress after bilateral common carotid artery occlusion. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2006 Jun;74(6):373–8. doi: 10.1016/j.plefa.2006.03.006

12. Bolduc V, Thorin-Trescases N, Thorin E. Endothelium-dependent control of cerebrovascular functions through age: exercise for healthy cerebrovascular aging. American Journal of Physiology-Heart and Circulatory Physiology. 2013 Sep 1;305(5):H620–33. doi: 10.1152/ajpheart.00624.2012

13. Cechetti F, Pagnussat AS, Worm PV, Elsner VR, Ben J, da Costa MS, et al. Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment. Brain Research Bulletin. 2012 Jan;87(1):109–16. doi: 10.1016/j.brainresbull.2011.10.006

14. Choi B-R, Lee SR, Han J-S, Woo S-K, Kim KM, Choi D-H, et al. Synergistic Memory Impairment Through the Interaction of Chronic Cerebral Hypoperfusion and Amlyloid Toxicity in a Rat Model. Stroke. 2011 Sep;42(9):2595–604. doi: 10.1161/strokeaha.111.620179

15. Choi D-H, Lee K-H, Kim J-H, Seo J-H, Kim HY, Shin CY, et al. NADPH Oxidase 1, a Novel Molecular Source of ROS in Hippocampal Neuronal Death in Vascular Dementia. Antioxidants & Redox Signaling. 2014 Aug;21(4):533–50. doi: 10.1089/ars.2012.5129

16. Chrishtop VV, Tomilova IK, Rumyantseva TA, Mikhaylenko EV, Avila-Rodriguez MF, Mikhaleva LM, et al. The Effect of Short-Term Physical Activity on the Oxidative Stress in Rats with Different Stress Resistance Profiles in Cerebral Hypoperfusion. Molecular Neurobiology. 2020 May 26;57(7):3014–26. doi: 10.1007/s12035-020-01930-5

17. Ding Y-H, Li J, Zhou Y, Rafols J, Clark J, Ding Y. Cerebral Angiogenesis and Expression of Angiogenic Factors in Aging Rats after Exercise. Current Neurovascular Research. 2006 Feb 1;3(1):15–23. doi: 10.2174/156720206775541787

18. Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, et al. Semax, an analog of ACTH(4–10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research. 2006 Oct 30;1117(1):54–60. doi: 10.1016/j.brainres.2006.07.108

19. Farkas E, Luiten PGM, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion- related neurodegenerative diseases. Brain Research Reviews. 2007 Apr;54(1):162–80. doi: 10.1016/j.brainresrev.2007.01.003

20. Kwon KJ, Kim MK, Lee EJ, Kim JN, Choi B-R, Kim SY, et al. Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia. Journal of the Neurological Sciences. 2014 Dec;347(1–2):66–77. doi: 10.1016/j.jns.2014.09.021

21. Liu J, Jin D-Z, Xiao L, Zhu X-Z. Paeoniflorin attenuates chronic cerebral hypoperfusioninduced learning dysfunction and brain damage in rats. Brain Research. 2006 May;1089(1):162–70. doi: 10.1016/j.brainres.2006.02.115

22. Ogoh S, Ainslie PN. Regulatory Mechanisms of Cerebral Blood Flow During Exercise. Exercise and Sport Sciences Reviews. 2009 Jul;37(3):123– 9. doi: 10.1097/JES.0b013e3181aa64d7

23. Ohtaki H, Fujimoto T, Sato T, Kishimoto K, Fujimoto M, Moriya M, et al. Progressive expression of vascular endothelial growth factor (VEGF) and angiogenesis after chronic ischemic hypoperfusion in rat. Acta neurochirurgica. Supplement. 2006; 96: 283–287. doi: 10.1007/3-211-30714-1_61

24. Ozkaya YG, Agar A, Yargiçoglu P, Hacioglu G, Bilmen-Sarikçioglu S, Ozen I, et al. The effect of exercise on brain antioxidant status of diabetic rats. Diabetes and Metabolism. 2002;28(5):377–84.

25. Querido JS, Sheel AW. Regulation of Cerebral Blood Flow During Exercise. Sports Medicine. 2007;37(9):765–82. doi: 10.2165/00007256-200737090-00002

26. Radak Z, Toldy A, Szabo Z, Siamilis S, Nyakas C, Silye G, et al. The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochemistry International. 2006 Sep;49(4):387–92. doi: 10.1016/j.neuint.2006.02.004

27. Schoenfeld R, Schiffelholz T, Beyer C, Leplow B, Foreman N. Variants of the Morris water maze task to comparatively assess human and rodent place navigation. Neurobiology of Learning and Memory. 2017 Mar;139:117–27. doi: 10.1016/j.nlm.2016.12.022

28. Servais S, Couturier K, Koubi H, Rouanet JL, Desplanches D, Sornay-Mayet MH, et al. Effect of voluntary exercise on H2O2 release by subsarcolemmal, and intermyofibrillar mitochondria. Free Radical Biology and Medicine. 2003;35(1):24–32. doi: 10.1016/s0891-5849(03)00177-1

29. Turtzo L, Lescher J, Janes L, Dean DD, Budde MD, Frank JA. Macrophagic and microglial responses after focal traumatic brain injury in the female rat. Journal of Neuroinflammation. 2014;11(1):82. doi: 10.1186/1742-2094-11-82