THE IMMUNOSUPPRESSANT FK506 AMELIORATES ISCHEMIC DAMAGE IN THE RAT-BRAIN

The effect of the immunosuppressant FK506 on ischaemic neuronal damage was studied in a rat model of transient cerebral ischemia induced by occlusion of both common carotid arteries in combination with hypotens ion for 10 min. Neuronal damage was assessed morphologically after 4 d ays of recovery. Treatment with FK506, given at a dose of 2 mg kg(-1) by intraperitoneal injections 30 min prior to ischemia and once daily during recovery, decreased neuronal damage by 52% in the hippocampal C A1 region and by 48% in the temporal cortex. The protection was nor du e to diminished body temperature or a marked reduction of ischaemia-in duced synaptic overflow of glutamate. We propose that FK506 decreases neuronal damage either by inhibiting calcineurin-mediated events or by preserving mitochondrial function.