Vasoactive and Neuroprotective Effects of c-Jun N-Terminal Kinase Inhibitor in Rats with Chronic Cerebral Hypoperfusion
Zhilyaev, S. Yu.
Platonova, T. F.
Khlebnikov, A. I.
Demchenko, I. T.
Atochin, D. N.
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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 common carotid artery ligation [two-vessel occlusion (2VO) model]. 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 2VO caused a decrease in blood flow in the brain regions with a more pronounced decrease in the cortex (by 48% of the initial level) and with a minimum 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 h for 14 days) was accompanied by an increase in blood flow in all brain regions. A maximum increase in blood flow was observed in the striatum and a 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 related neurological disorders in hypoperfusion brain injury.
copyright Pleiades Publishing Ltd 2023
Zhilyaev, S.Y., Platonova, T.F., Khlebnikov, A.I. et al. Vasoactive and Neuroprotective Effects of c-Jun N-Terminal Kinase Inhibitor in Rats with Chronic Cerebral Hypoperfusion. J Evol Biochem Phys 59, 951–959 (2023). https://doi.org/10.1134/S0022093023030262