The immunosuppressant FK506 ameliorates ischaemic 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 hypotension for 10 min. Neuronal damage was assessed morphologically after 4 days 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 CA1 region and by 48% in the temporal cortex. The protection was not due to diminished body temperature or a marked reduction of ischaemia-induced synaptic overflow of glutamate. We propose that FK506 decreases neuronal damage either by inhibiting calcineurin-mediated events or by preserving mitochondrial function.
Laboratory for Experimental Brain Research, University of Lund, Lund University Hospital, Sweden. tadeusz.wieloch@eforsk.lu.se
M
M
Drake
H
H
Friberg
F
F
Boris-Möller
K
K
Sakata
T
T
Wieloch
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000494:pharmacology*
D018698:Glutamic Acid; D016559:Tacrolimus