Morphological changes in the hippocampus of the rat brain in ischemia and in conditions of combined preconditioning

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Аннотация

BACKGROUND: Preconditioning is effective for increasing the body’s resistance to hypoxia/ischemia. AIM: To evaluate morphological changes in the most hypoxia-sensitive fields of the hippocampus CA1 and CA3 in cerebral ischemia in rats and under conditions of combined preconditioning. MATERIALS AND METHODS: Cerebral ischemia was simulated in rats under anesthesia (8% chloral hydrate solution, 400 mg/kg) by bilateral ligation of the common carotid arteries. The combined preconditioning method included the alternate use of two preconditional factors: pharmacological (amtisol, 25 mg/kg) and hypoxic (hypobaric hypoxia, 410 mmHg; exposure time, 60 min). Morphometric assessment of brain damage was performed a day after modeling ischemia in the CA1 and CA3 fields of the hippocampus. RESULTS: Combined preconditioning has a positive effect on the morphometric parameters of the brain during ischemia, including increasing neuronal survival in the early and late periods of ischemia modeling, preventing the formation of necrotically and apoptotically altered neurons, hyperactivation of microglial cells, and contributing to endotheliocyte preservation. CONCLUSIONS: Combined preconditioning (amtisol + hypobaric hypoxia) has a neuroprotective effect in cerebral ischemia.

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Авторлар туралы

V. Novikov

Smolensk State Medical University

Хат алмасуға жауапты Автор.
Email: nau@sgmu.info
ORCID iD: 0000-0002-0953-7993
SPIN-код: 1685-1028

Professor, Doctor of Medical Sciences, Head of the Department of Pharmacology

Ресей, Krupskaya St., 28, Smolensk, 214019

O. Levchenkova

Smolensk State Medical University

Email: os.levchenkova@gmail.com
ORCID iD: 0000-0002-9595-6982
SPIN-код: 2888-6150

MD, Dr. Sci. (Medicine), Assistant Professor

Ресей, Smolensk

J. Korneva

Smolensk State Medical University

Email: nau@sgmu.info
ORCID iD: 0000-0002-8080-904X
SPIN-код: 5169-7740

MD, Cand. Sci. (Medicine), Assistant Professor

Ресей, Smolensk

Әдебиет тізімі

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  2. Novikov VE, Levchenkova OS, Pozhilova EV. Preconditioning as a method of metabolic adaptation to hypoxia and ischemia. Vestnik of the Smolensk State Medical Academy. 2018;17(1):69–79. EDN: YXHXPI
  3. Hao Y, Xin M, Feng L, et al. Review cerebral ischemic tolerance and preconditioning: methods, mechanisms, clinical applications, and challenges. Front Neurol. 2020;11:812. doi: 10.3389/fneur.2020.00812
  4. Zenko MYu, Rybnikova EA. Pharmacological preconditioning. Integrative physiology. 2020;1(1):32–39. EDN: CDEKPO doi: 10.33910/2687-1270-2020-1-1-32-39
  5. Levchenkova OS, Kulagin KN, Novikov VE. Cerebroprotective action of pharmacological and hypoxic preconditioning in brain ischemia. Vestnik of the Smolensk State Medical Academy. 2017;16(2):15–21. EDN: YPCMXX
  6. Levchenkova OS, Novikov VE. Possibilities of pharmacological preconditioning. Annals of the Russian academy of medical sciences. 2016;71(1):16–24. EDN: VPLXBD doi: 10.15690/vramn626
  7. Novikov VE, Levchenkova OS. Perspectives of use of inducers of the hypoxia adaptation factor in therapy of ischemic diseases. Journal of Ural medical academic science. 2014;(5):132–138. EDN: TKZNBL
  8. Yang Y, Lu F, Huang L, et al. Combined preconditioning with hypoxia and GYKI-52466 protects rats from cerebral ischemic injury by HIF-1a/eNOS pathway. Am J Transl Res. 2017;9(12):5308–5319.
  9. Novikov VE, Levchenkova OS, Klimkina EI, Kulagin KN. Potentiation of the hypoxic preconditioning effect by antihypoxants. Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(1):37–44. EDN: PHNAKT doi: 10.7816/RCF17137-44
  10. Levchenkova OS, Novikov VE, Kulagin KN, Ponamareva NS. Influence of combined pharmacological and hypoxic preconditioning on animal survival and functional activity of CNS during model cerebral ischemia. Experimental and clinical pharmacology. 2016;79(6):3–8. EDN: WCOGFF doi: 10.30906/0869-2092-2016-79-6-3-8
  11. Levchenkova OS, Novikov VE, Parfenov EA, Kulagin KN. Neuroprotective effect of antioxidants and moderate hypoxia as combined preconditioning in cerebral ischemia. Bulletin of Experimental Biology and Medicine. 2016;162(8):173–177. EDN: WHHGMP
  12. Novikov VE, Levchenkova OS. Erythropoietin and vascular endothelial growth factor level in normoxia and in cerebral ischemia under pharmacological and hypoxic preconditioning. Biomedical chemistry. 2020;(4):339–344. EDN: XDXCGU doi: 10.18097/PBMC2020664339
  13. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. Hard Cover Edition: Academic Press, 2007. 456 p.
  14. Novikov VE, Sharov AN. Effect of GABAergic agents on oxidative phosphorylation in brain mitochondria in traumatic brain oedema. Pharmacology and toxicology. 1991;54(6):44–46. (In Russ.)
  15. Pozhilova EV, Novikov VE, Levchenkova OS. Reactive oxygen species in cell physiology and pathology. Vestnik of the Smolensk State Medical Academy. 2015;14(2):13–22. EDN: UHOVFR
  16. Novikov VE, Ponamaryova NS, Shabanov PD. Aminothiol antihypoxants in traumatic brain oedema. Saint Petersburg: Elby-SPb; 2008. 176 p. (In Russ.)
  17. Novikov VE, Kulagin KN, Levchenkova OS, Ponamareva NS. Influence of preconditioning by amtizol and moderate hypoxia on brain mitochondrial function under experimental normoxia/cerebral ischemia conditions. Experimental and clinical pharmacology. 2019;82(12):3–8. EDN: WDPYUW doi: 10.30906/0869-2092-2019-82-12-3-8
  18. Novikov VE, Levchenkova OS, Pozhilova EV. Pharmacological preconditioning: opportunities and prospects. Vestnik of the Smolensk State Medical Academy. 2020;19(2):36–49. EDN: OMTYRF doi: 10.37903/vsgma.2020:2.6
  19. Novikov VE, Pozhilova EV. Pharmacological neuroprotection in cerebrovascular insufficiency: Possible approaches. Psychopharmacology and biological narcology. 2024;15(1):23–32. EDN: ZZEGEE doi: 10.17816/phbn626125
  20. Evseev AV, Mosin OA, Evseeva MA, et al. Antihypoxic effect of almid-containing metal-complex compounds in the experiment. Psychopharmacology and biological narcology. 2024;15(1):53–60. EDN: EAKJEE doi: 10.17816/phbn626030
  21. Levchenkova OS, Novikov VE, Vorobyova VV, Kulagin KN. Activity of ROS-induced processes in the combined preconditioning with amtizol before and after cerebral ischemia in rats. Res Results Pharmacol. 2021;7(2):49–57. doi: 10.3897/rrpharmacology7.66808

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2. Fig. 1. Zones CA1 (a, c, e) and CA3 (b, d, f) fields of the hippocampus of the rat brain with simulated ischemia. The histoarchitecture is unclear, cellularity is sharply reduced, pronounced pericellular edema, foci of destruction in the brain tissue. e, f: in both zones, there are no normal neurons, and almost all neurons are hyperchromatic, wrinkled, reduced in size, lacking processes; single sharply swollen macroglial cells are detected; capillaries are not detected; maximum number of microglial cells. Hematoxylin–eosin staining. Magnification for a, b, c × 200, for d × 100, for e, f × 400

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3. Fig. 2. Zones CA1 (a, c) and CA3 (b, d) of the hippocampus of the rat brain (combined preconditioning with amtizol, early period). The histoarchitecture can be traced, the cellularity is relatively preserved, and there is pronounced perivascular and, in some places, pericellular edema. Both zones: single normal neurons are found (more in the CA3 field); hyperchromic neurons are present. CA1 field: shadow cells and hypochromic neurons are detected; macroglia are partially preserved; capillaries are identified, but their endothelium is absent in places; single microglial cells appear. Hematoxylin–eosin staining. Magnification for a, b × 200, for c, d × 400

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