Neuroprotective effects of cortexin and ischemic preconditioning

Abstract

The purpose was to assess neuroprotective effects of cortexin and ischemic preconditioning in rats with occlusion of both carotid arteries. Methods. The Wistar rats were divided into two groups according to their resistance to hypoxia. All rats were raised in barocamera on altitude 11 000 m with speed 50 m/sec and exposition up to agonal breath. Rats resistant to hypoxia more than 10 min were qualified as high resistant (HR), less than 5 min as low resistant (LR) to hypoxia. Ischemic preconditioning was reproduced by the 3-times temporary occlusions of common carotid arteries (5 min each) with 15-min reperfusion interval between occlusions. The chronic ischemia was modeled by means of ligation (permanent occlusion) of both carotid arteries in 1 h (early preconditioning) or 24 h (delayed preconditioning) after preconditioning procedure. Cortexin 1 mg/kg was administered intraperitoneally 7 days after occlusion of carotid arteries. Neurological status was assessed using McGrow’s stroke-index. Results. In postischemic period, the functional and metabolic changes in the brain of HR and LR rats were more significant in conditions of delayed preconditioning. In group of early preconditioning, a number of survival rats on 7th day was more than in delayed preconditioning group. Cortexin administration (1 mg/kg, 7 days) increased quantity of survival rats, especially in delayed preconditioning group. The maximal effect of cortexin was observed in delayed preconditioning group. Also cortexin decreased malonic dialdehyde level and increased superoxide dismutase activity of the brain tissue in all groups of rats. Conclusion. The course administration of polypeptide drug cortexin reduces neurological deficit signs, recovers structure of individual behavior of rats with different resistance to hypoxia and performs antioxidant action in chronic ischemic damage of the brain on the background of early and delayed preconditioning.