Effect of Tacrolimus on pyramidal cells of cerebral cortex in experimental brain ischemia model in Wistar rat

Cerebral ischemia is known as a main cause of morbidity and mortality in the world and there was no effective treatment yet. Global cerebral ischemia causes loss of pyramidal cells of brain cortex following global ischemic/reperfusion. Recently، using immunophilin ligands has been considered as a potential and appropriate strategy for neuroprotection. Since it was observed that tacrolimus (FK506)، a useful immunosuppressant used in organ transplantation، provides neuroprotection and prevents neuronal damage،the importance of immunophilins in the development of neuroprotectors has emerged. In this study، we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. In this experimental study، 25 Wistar rats were assigned to control (intact)، ischemia and 3 FK506 treated (1،3،6 mg/kg) groups. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In 3 experimental groups، tacrolimus or FK506 was given as a single dose exactly at the time of reperfusion respectively as 1، 3، 6 mg/kg by intravenous administration (IV). The same doses repeated by intraperitoneally administration (IP) 48 hours after reperfusion. After 4 days، the rats were sacrificed and brain sections were stained by H & E and Nissl. Our findings showed that 20 min ischemia decreased the number of the cortex pyramidal cells. But there were significant differences between number of cortex pyramidal cells in ischemia and FK506 (6mg/kg) groups. Our study suggests that tacrolimus has a neurotrophic effect on pyramidal cells of brain cortex and may candidate for treatment of ischemia brain damage.