Stepwise Cerebral Ischemia Causes Disturbances in Mitochondrial Respiration of Neurons in the Cerebral Cortex of Rats

Abstract

Objectives: To conduct a comparative analysis of respiration of mitochondria of brain homogenates of rats with stepwise subtotal cerebral ischemia with different duration between ligations of both common carotid arteries. Methods: The experiments were performed on 24 male mongrel white rats weighing 260 ±20 g. Cerebral ischemia (CI) was simulated under intravenous thiopental anesthesia (40-50 mg/kg). The control group consisted of falsely operated rats of similar sex and weight. To study mitochondrial respiration, the brain was extracted in the cold (0-4°C), dried with filter paper, weighed and homogenized in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH 7.4 (in a ratio of 1:10), using Potter-Evelheim homogenizer with Teflon pestle according to the modified method. To prevent systematic measurement errors, brain samples from the compared control and experimental groups of animals were studied under the same conditions. Results: Stepwise SCI with an interval of 1 and 3 days between bandages of both OCA leads to damage to the neurons of the parietal cortex and hippocampus of rats, which manifests itself in a decrease in their size, deformation of the pericaryons, an increase in the number of shrunken neurons and shadow cells. The most pronounced changes were observed in the subgroup with an interval between dressings of 1 day. These changes were similar to the changes in SCI (p>0.05), except for the absence of cells with pericellular edema in the hippocampus and a smaller number of them in the parietal cortex. SCI with an interval between WASP dressings of 7 days, on the contrary, it is manifested by less pronounced histological changes, especially in the hippocampus. Conclusion: In cerebral ischemia, damage to the inner mitochondrial membrane occurs due to activation of free radical oxidation processes. Damage to the inner mitochondrial membrane, in turn, leads to an increase in its permeability and a decrease in the level of the proton gradient due to the transition of protons along the concentration gradient through the resulting nonspecific pores into the mitochondrial matrix. As a result, the efficiency of ATP synthesis decreases, and more substrates and oxygen are required to maintain the intermembrane potential under these conditions.