Antiedematous activity of cerebrocrastin cerebral ischemia

Abstract

The effect of a course of cerebrocrast, a 1,4-dihydropyridine derivative, on brain edema (as shown by impedometry) and cerebral tissue microvascularization in ischemia caused by ligation of the left common carotid artery and 50% restriction of the bloodflow in the right common carotid artery is studied in Wistar rats. Cerebrocrast is found to appreciably limit the development of brain tissue edema and to improve the status of microvessels by reducing the number of sharply constricted nonfunctioning capillaries and increasing the number of capillaries of 4 ~t and more in diameter. Pronounced antioxidative effects of cerebrocrast in transitory cerebral ischemia are demonstrated. Key Words: cerebrocrast; brain ischemia; brain edema; microcirculation; lipid peroxidationRecent experimental and clinical data indicate that the effect of Ca antagonists belonging to the 1,4-dihydropyridines, which is associated with functional protection of the brain, can be manifested irrespective of their influence on the blood supply to the brain [13,14]. For example, a course of treatment with cerebrocrast (CC), a 1,4-dihydropyridine derivative, administered to alert rats after the induction of brain ischemia was associated with a positive impact on the bioelectrical activity of the cerebral cortex which anticipated the recove l i of the blood supply to the respective brain areas [2]. Bearing in mind the antiedematous effect of these drugs under conditions of ischemic edema of the brain [9,15], we examined the effect of CC on the time course of edematous swelling of the cerebral cortex in alert rats on a model of cerebral ischemia and studied some mechanisms of this effect. MATERIALS AND METHODSExperiments were carried out on male Wistar rats weighing 220 to 270 g. The degree of edematous swelling of brain tissue in alert rats was assessed by the method of impedance recording in our modification. For this purpose, bipolar platinum electrodes were implanted in 18 animals (6 controis and 12 experimental rats) under narcosis (sodium ethaminal in a dose of 50 mg/kg intraperitoneally) 6-7 days before the experiment. Complete impedance and its constituents were recorded with an 1-2 impedometer. The microcirculatory bed was examined in 18 rats (6 sham-operated, 6 controls, and 6 experimental) by the modified calcium adenosine triphosphate method [8]. With reference to the mean diameter of red cells and their deformability [3], capillaries 2+1 ~t in diameter were considered as severely constricted and nonfunctioning.Brain ischemia in control and experimental rats of the above series was reproduced under ether narcosis by complete ligation of the left common carotid artery and restriction of the bloodflow in