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Common Carotid Artery Occlusion and Double-Nucleated Cellular Structures In The Rat Sensorimotor Cerebral Cortex

https://doi.org/10.15360/1813-9779-2021-2-55-71

Abstract

The aim of the study. To study the double-nucleated cellular structures of the brain sensorimotor cortex (SMC) of sexually mature white rats after a 40-minute occlusion of the common carotid arteries.

Methods. Acute ischemia was simulated in white Wistar rats by 40-minute occlusion of the common carotid arteries (OCCA). We performed comparative morphometric evaluation of cyto-, dendro-, synapto-, and glioar-chitectonics of the neocortex in intact animals (n=5), and 1 (n=5), 3 (n=5), and 7 days (n=5) after OCCA. We used Nissl, hematoxylin and eosin staining, and immunohistochemical reactions for NSE, MAP-2, HSP-70, p38, caspase-3, GFAP, AIF1, and Ki-67. Numerical density of pyramidal neurons, oligodendrocytes (ODCs), mi-croglyocytes (MGCs), presence of dystrophic and necrobiotic neurons with one or more nucleoli, hetero- and dikaryons were assessed. Statistical hypotheses were tested using Statistica 8.0 software.

Results. The percentage of dystrophic and necrobiotic neurons, nerve cells with two nuclei or two or more nucleoli, the total number (proliferation) and percentage of hypertrophic astrocytes, ODCs and MGCs increased significantly after OCCA. The total numerical density of SMC neurons decreased by 26.4% (P=0.001) in layer III and by 18.5% in layer V (Mann-Whitney U Test; P=0.01) after OCCA throughout the observation period. Pathological and compensatory changes were diffusely focal and more pronounced in layer III of the neocortex. The density of bi-nucleated heterokaryons and dikaryons remained unchanged on days 1 and 3 after OCCA vs control and was 3.5 (1.5-4.0)/mm2, and increased to 6.5 (5.0-8.5)/mm2 on day 7 (Mann-Whitney U Test; P=0.002). This increase occurred along with a higher density of ODCs and MGCs than in the control. The maximum number of neurons with two or more nucleoli was also noted in layer III and V during this period.

Conclusion. After 40-minute OCCA in SMC, parallel to the dystrophic and necrobiotic changes of pyramidal neurons and activation of neuroglial cells, there was an increase in the formation of heterokaryons and neurons with amplified nucleolus. These changes were considered as a variant of neuronal response to ischemic damage.

About the Authors

D. B. Avdeev
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Dmitry B. Avdeev.

12 Lenin Str., 644099 Omsk.



V. A. Akulinin
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Victor A. Akulinin.

12 Lenin Str., 644099 Omsk.



S. S. Stepanov
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Sergei S. Stepanov.

12 Lenin Str., 644099 Omsk.



A. Yu. Shoronova
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Anastasia Yu. Shoronova.

12 Lenin Str., 644099 Omsk.



L. M. Makarieva
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Lyubov M. Makarieva.

12 Lenin Str., 644099 Omsk.



A. V. Gorbunova
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Anna V. Gorbunova.

12 Lenin Str., 644099 Omsk.



M. S. Korzhuk
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Mikhail S. Korzhuk.

12 Lenin Str., 644099 Omsk.



M. V. Markelov
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

Marina V. Markelov.

12 Lenin Str., 644099 Omsk.



References

1. Avrushchenko M.S., Ostrova I.V. Postresuscitative Changes of Brain-Derived Neurotrophic Factor (BDNF) Protein Expression: Association With Neuronal Death. Obshchaya Reanimatologiya=General Reanimatology. 2017; 13 (4): 6-21 [In Russ.]. DOI: 10.15360/1813-9779-2017-4-6-21

2. Stepanov S.S., Akulinin V.A., Avdeev D.B., Stepanov A.S., Gorbunova A.V. Structural and functional reorganization of the nucleolar apparatus of neurons of the neocortex, archicortex, and basal ganglia of the brain of white rats after 20-minute occlusion of the common carotid arteries. Zhurnal anatomii i gistopatologii. 2018; 7 (4): 67-74 [In Russ.]. DOI: 10.18499/2225-7357

3. Stepanov A.S., Akulinin V.A., Stepanov S.S., Avdeev D.B. Cellular systems of restoration and utilization of damaged neurons of the brain of white rats after 20-minute occlusion of the common carotid arteries. Rossijskij fiziologicheskij zhurnal im. I.M. Sechenova. 2017; 103 (10): 1135-1147 [In Russ.].

4. Stepanov A.S., Akulinin V.A., Mysik A.V., Stepanov S.S., Avdeev D.B. Neuro-Glio-Vascular Complexes of the Brain After Acute Ischemia. Obshchaya Reanimatologiya=General Reanimatology. 2017; 13 (6): 6-17. [In Russ.]. DOI: 10.15360/1813-9779-2017-6-6-17

5. Oksanen M., Lehtonen, S., Jaronen, M., Goldsteins, G., Hamalainen R.H., Koistinaho J. Astrocyte alterations in neurodegenerative pathologies and their modeling in human induced pluripotent stem cell platforms. Cellular and Molecular Life Sciences. 2019; 76: 27392760. DOI: 10.1007/s00018-019-03111-7

6. Sakharnova T.A., Vedunova M.V., Mukhina I.V. Neurotrophic factor of the brain (BDNF) and its role in the functioning of the central nervous system. Neirokhimiya. 2012; 29 (4): 269-277 [In Russ.].

7. Mitroshina E.V., Abogessimengane B.Zh., Urazov M.D., Khamrauy I., Mishchenko T.A., Astrakhanova T.A., Shchelchkova N.A., Lapshin R.D., Shishkina T.V., Belousova I.I., Mukhina I.V., Vedunova M.V. Adaptive role of glial neurotrophic factor in cerebral ischemia. Sovremennye tekhnologii v meditsine. 2017; 9 (1): 68-77 [In Russ.]. DOI: 10.17691/stm2017.9.1.08

8. Alekseeva O.S., Kirik O.V., Gilerovich E.G., Korzhevsky D.E. Brain microglia: origin, structure and functions. Evolyutsionnoj biokhimii i fiziologii. 2019; 55 (4): 231-241 [In Russ.]. DOI: 10.1134/S0044452919040028

9. Kalinina Yu.A., Gilerovich E.G., Korzhevsky D.E. Astrocytes and their participation in the mechanisms of therapeutic action of multipotent mesenchymal stromal cells in ischemic brain damage. Geny i kletki. 2019; 14 (1): 33-40 [In Russ.]. DOI: 10.23868/201903004

10. Pekny M., Pekna M. Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiol Rev. 2014; 94: 1077-1098. DOI: 10.1152/physrev.00041.2013

11. Cowan M., Petri Jr. W. A. Microglia: Immune regulators of neurodevelopment. Frontiers in immunology. 2018; 9: 2576. DOI: 10.3389/fimmu.2018.02576

12. Chen Z., Zhong, D., Li, G. The role of microglia in viral encephalitis: a review. Journal of Neuroinflammation. 2019; 16: 76. DOI: 10.1186/s12974-019-1443-2

13. Sotnikov O.S., Frumkina L.E., Laktionova A.A., Paramonova N.M., No-vakovskaya S.A. Binuclear neurons: syncytial fusion or amitosis. Uspekhi fiziologicheskih nauk. 2011; 42 (4): 76-89 [In Russ.]. PMID: 22145312

14. Sotnikov O.S., Frumkina L.E., Novakovskaya S.A., Bogolepov N.N. Fusion of brain neurons in rat embryos. Morfologiya. 2011; 139 (2): 18-21 [In Russ.]. PMID: 21866800

15. Kemp K., Wilkins A., Scolding N. Cell fusion in the brain: two cells forward, one cell back. Acta Neuropathol. 2014; 128: 629-638. DOI: 10.1007/s00401-0141303-1

16. Pereira M., Birtele M., Rylander Ottosson D. Direct reprogramming into interneurons: potential for brain repair. Cellular and Molecular Life Sciences. 2019; 76: 3953-3967. DOI: 10.1007/s00018-019-03193-3

17. Sviridkina N.B., Shakova F.M., Komissarova S.V., Dubrovin I.P., Tury-gina S.A., Romanova G.A., Baranova V.M. Morphofunctional study of the effect of antiorthostatic hypokinesia in focal ischemic damage to the cerebral cortex. Patologicheskaya fiziologiya i eksperimental'naya terapiya.2012; 2: 22-26. PMID: 22708403

18. Krishtop V.V., Nikonorova V.G., Rumyantseva T.A. Changes in the cellular composition of the cerebral cortex in rats with different levels of cognitive functions in cerebral hypoperfusion. Vestnik Rossijskogo universiteta druzhby narodov. 2019; 8 (4): 22-29 [In Russ.]. DOI: 10.18499/2225-7357-2019-8-4-22-29

19. Paltsyn A.A., Manukhina E.B., Goryacheva A.V., Downey H.F., Dubrovin I.P., Komissarova S.V., Kubatiev A.A. Intermittent hypoxia stimulates formation of binuclear neurons in brain cortex - A role of cell fusion in neuroprotection? Experimental Biology and Medicine. 2014; 239: 595-600. DOI: 10.1177/1535370214523898

20. Paltsyn A.A., Sviridkina N.B. On brain regeneration (lecture II). Pato-genes; 16 (1): 83-91 [In Russ.]. DOI: 10.25557/2310-0435.2018.01.83-91

21. Morgun A.V., Malinovskaya N.A., Komleva Yu.K., Lopatina O.L., Ku-vacheva N.V., Panina Yu.A., Taranushenko T.E., Solonchuk R.Yu., Salmina A.B. Structural and functional heterogeneity of brain astrocytes: the role in neurodegeneration and neuroinflammation. Byul-leten' sibirskoj meditsiny. 2014; 13 (5): 138-148 [In Russ.]. DOI: 10.20538/1682-0363-2014-5-138-148

22. Sankavaram S.R., Svensson M.A., Olsson T., Brundin L., Johansson C.B. Cell fusion along the anterior-posterior neuroaxis in mice with experimental autoimmune encephalomyelitis. PLoS One. 2015; 10 (7): e0133903. DOI: 10.1371/journal.pone.0133903

23. Giordano-Santini R., Linton C., Hilliard M.A. Cell-cell fusion in the nervous system: Alternative mechanisms of development, injury, and repair. Semin. Cell Dev. Biol. 2016; 60: 146-54. DOI: 10.1016/j.sem-cdb.2016.06.019

24. Kravtsov V., Oren-Suissa M., Podbilewicz B. The fusogen AFF-1 can rejuvenate the regenerative potential of adult dendritic trees by selffusion. Development. 2017; 144 (13): 2364-74. DOI: 10.1242/dev.150037

25. Espejel S., Romero R., Alvarez-Buylla A. Radiation damage increases Purkinje neuron heterokaryons in neonatal cerebellum. Ann. Neurol. 2009; 66: 100-109. DOI: 10.1002/ana.21670

26. Kemp K., Gray E., Wilkins A., Scolding N. Purkinje cell fusion and binucleate heterokaryon formation in multiple sclerosis cerebellum. Brain. 2012; 135: 2962-2972. DOI: 10.1002/ana.21670

27. Yushkov B.G. Cells of the immune system and regulation of regeneration. Byulleten' sibirskoj mediciny. 2017; 16 (4): 94-105. DOI: 10.20538/1682-0363-2017-4-94-105

28. Ackman J.B., Siddiqi F., Walikonis R.S., LoTurco J.J. Fusion of microglia with pyramidal neurons after retroviral infection. J. Neurosci. 2006; 26: 11413-11422. DOI: 10.1523/JNEUROSCI.3340-06.2006

29. Sotnikov O.S. The reticular theory of Camillo Golgi and the rearrangement of electrical synapses into syncytial perforations. Izvestiya RAN. Seriya biologicheskaya. 2019; 2: 127-143 [In Russ.]. DOI: 10.1134/S0002332919020140

30. Avdeev D.B., Akulinin V.A., Stepanov A.S., Gorbunova A.V., Stepanov S.S. Pleiotropic enzymes of apoptosis and synaptic plasticity of the hippocampus of white rats after occlusion of the common carotid arteries. Sibirskij medicinskij zhurnal (Tomsk). 2018; 33 (3): 102-110 [In Russ.]. DOI: 10.29001/2073-8552-2018-33-3-102-110

31. Borovikov V. Statistica. The art of analyzing data on a computer. Publishing House «Piter»; 2003: 2nd ed.: 688 [In Russ.].

32. Giordano-Santinia R., Kaulicha E., Galbraitha K.M., Ritchiea F.K., Wangb W., Lib Z., Hilliarda M.A. Fusogen-mediated neuron-neuron fusion disrupts neural circuit connectivity and alters animal behavior. PNAS. 2020; 117 (37): 23054-23065. DOI: 10.1073/pnas.1919063117

33. Alvarez-Dolado M., Martinez-Losa M. Cell fusion and tissue regeneration. Adv. Exp. Med. Biol. 2011; 713: 161-175. DOI: 10.1007/978-94-007-0763-4_10

34. Kosi N., Alic I., Kolacevic M., Vrsaljko N., Jovanov Milosevic N., Sobol M., Philimonenko A., Hozak P., Gajovic S., Pochet R., Mitrecic D. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain. Brain Res. 2015; 1597: 65-76. DOI: 10.1016/j.brainres.2014.11.040

35. Damisah E.C., Hill R.A., Rai A., Chen F., Ghosh S., Grutzendler J. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Science Advances. 2020; 6 (26): eaba3239. DOI: 10.1126/sciadv.aba3239


Review

For citations:


Avdeev D.B., Akulinin V.A., Stepanov S.S., Shoronova A.Yu., Makarieva L.M., Gorbunova A.V., Korzhuk M.S., Markelov M.V. Common Carotid Artery Occlusion and Double-Nucleated Cellular Structures In The Rat Sensorimotor Cerebral Cortex. General Reanimatology. 2021;17(2):55-71. https://doi.org/10.15360/1813-9779-2021-2-55-71

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ISSN 1813-9779 (Print)
ISSN 2411-7110 (Online)