Microbiology & Cell Biology
Permanent URI for this communityhttps://scholarworks.montana.edu/handle/1/10
Browse
2 results
Search Results
Item Vasoactive and Neuroprotective Effects of c-Jun N-Terminal Kinase Inhibitor in Rats with Chronic Cerebral Hypoperfusion(Pleiades Publishing Ltd, 2023-05) Zhilyaev, S. Yu.; Platonova, T. F.; Khlebnikov, A. I.; Demchenko, I. T.; Atochin, D. N.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.Item Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction(MDPI AG, 2023-02) Plotnikov, Mark B.; Chernysheva, Galina A.; Smol’yakova, Vera I.; Aliev, Oleg I.; Fomina, Tatyana I.; Sandrikina, Lyubov A.; Sukhodolo, Irina V.; Ivanova, Vera V.; Osipenko, Anton N.; Anfinogenova, Nina D.; Khlebnikov, Andrei I.; Atochin, Dmitriy N.; Schepetkin, Igor A.; Quinn, Mark T.Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11H-indeno [1,2-b]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI.