Vasoactive and Neuroprotective Action of с-Jun-N-Terminal Kinases Inhibitor in Rats with Chronic Brain Hypoperfusion

S. Yu. Zhilyaev; Жиляев С. Ю.; T. F. Platonova; Платонова Т. Ф.; A. I. Khlebnikov; Хлебников А. И.; I. A. Schepetkin; Щепёткин И. А.; I. T. Demchenko; Демченко И. Т.; D. N. Atochin; Аточин Д. Н.

doi:10.31857/S0869813923060079

Vasoactive and Neuroprotective Action of с-Jun-N-Terminal Kinases Inhibitor in Rats with Chronic Brain Hypoperfusion

Authors: Zhilyaev S.Y.¹, Platonova T.F.¹, Khlebnikov A.I.², Schepetkin I.A.²^,3, Demchenko I.T.¹, Atochin D.N.²^,4
Affiliations:
1. Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences
2. Tomsk Polytechnic University
3. Department of Microbiology and Cell Biology, Montana State University
4. Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School
Issue: Vol 109, No 6 (2023)
Pages: 749-759
Section: EXPERIMENTAL ARTICLES
URL: https://kazanmedjournal.ru/0869-8139/article/view/651558
DOI: https://doi.org/10.31857/S0869813923060079
EDN: https://elibrary.ru/WHDHHT
ID: 651558

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Abstract

The aim of this study was to evaluate the vasoactive and neuroprotective effects of c-Jun-N-terminal kinase inhibitor IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) in chronic cerebral hypoperfusion caused by irreversible bilateral ligation of carotid arteries. Cerebral blood flow was measured quantitatively (hydrogen clearance method) simultaneously in the parietal cortex, hippocampus, substantia nigra, and striatum of the brain of awake rats. It was found that ligation of the carotid arteries caused a decrease in blood flow in the brain structures with a more pronounced decrease in the cortex (by 48% of the initial level) and with the smallest drop in the substantia nigra (by 25% of the initial level). The reduced level of blood flow persisted for 14 days of measurements. The responses of the cerebral vessels to hypercapnic probes (5% CO₂) were lost during the 2-week hypoperfusion period, and the neurological status of the animals did not improve. The administration of IQ-1 (50 mg/kg, intraperitoneally, every 48 hours for 14 days) was accompanied by an increase in blood flow in all brain structures. The maximum increase in blood flow was observed in the striatum and the minimum in the substantia nigra. After the administration of IQ-1, the sensitivity of the cerebral vessels to the hypercapnic stimulus was restored and the neurological state of the animals significantly improved by the end of the second week of cerebral hypoperfusion. The results show that the use of the JNK inhibitor can reduce cerebrovascular disorders and associated neurological disorders in hypoperfusion brain injury.

Keywords

c-Jun-N-terminal kinase inhibitors, chronic cerebral hypoperfusion, cerebral blood flow, neuroprotection, hypercapnic probe, striatum, substantia nigra

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