Neuroprotective Treatment With FK506 Reduces Hippocampal Damage and Prevents Learning and Memory Deficits After Transient Global Ischemia in Rat

Behavioral studies on animals demonstrated that hippocampal damage could produce learning and memory impairments particularly spatial learning. It has been shown that ischemic damage restricted to only 50% of the CA1 cells of the hippocampus exceed the threshold for production of a behavioral impairment. In this study we seek to evaluate the effect of FK506 (tacrolimus) on spatial learning of rats subjected to 20-min global transient ischemia/reperfusion. In experimental group1, FK506 (1mg/kg) was given intravenously (IV) 20 minutes before ischemia and in experimental group2 rats were treated with the same dose of tacrolimus (IV) at the beginning of reperfusion. Morris water maze tests were performed 1 week after ischemia for 4 days. Brain tissue proceeded to TUNEL staining. Our data showed; 1) No statistically significant differences were seen between the experimental group1 and the control (intact) group thus, this suggests that treatment of ischemia with tacrolimus can improve spatial learning and memory. 2) Tacrolimus treatment ameliorated the increase of TUNEL–positive cells induced by cerebral ischemia indicating the neuro-protective properties of FK506. These results suggest that tacrolimus may reduce cognitive impairment and may be a good candidate for treatment of ischemic brain damage.