Postresuscitation Changes in the Expression of Glial-Derived Neurotrophic Factor (GDNF): Association with Cerebellar Purkinje Cell Damage (An experimental study)
Objective: to determine the significance of the expression of GDNF protein for developing a cerebellar Purkinje cell death process after ischemia-reperfusion. Materials and methods. Rats of both sexes were subjected to 10 minutes of systemic circulatory arrest caused by cardiac vascular fascicle ligation. The status of a highly hypoxia-sensitive neuronal population of cerebellar Purkinje cells was investigated in different postresuscitation periods. The total number of Purkinje cells per mm of their layer length was estimated by a histological analysis of the specimens stained with cresyl violet after the Nissl procedure. An immunocytochemical analysis was made to determine the number of GDNF-positive (weakly and strongly stained) and GDNF-negative neurons per mm of their layer length and the total population density. Results. The histological and immunocytochemical studies of resuscitated male and female rats have determined a trend in the development of a neuron death process in the population of cerebellar Purkinje cells and revealed postresuscitation changes in the level of GDNF protein expression. Homogeneous and unidirectional postresuscitation changes have been ascertained to develop in the Purkinje cell population of the animals of both sexes. The initial rise in the expression of GDNF protein in the neuronal population can prevent the development of a nerve cell death process. The subsequent decrease in GDNF expression is accompanied by neuronal fallout (death). At the same time, GDNF-negative cells may undergo death. There are gender- specific features; the male rats show changes in GDNF expression in the Purkinje cell population and develop neuronal death processes earlier than the female rats. Conclusion. There was an association between the changes in GDNF protein expression and the development of a neuronal death process in the postresuscitation period. The GDNF protein expression was shown to be an important factor influencing the resistance of neurons to death in the postresuscitation period. This determines prospects for using GDNF to elaborate approaches to protecting the brain in ischemia-reperfusion.