Blockade of the mitochondrial permeability transition pore diminishes infarct size in the rat after transient middle cerebral artery occlusion.
The mitochondrial permeability transition pore is an inducer of cell death. During the reperfusion phase after cerebral ischemia, calcium accumulates in mitochondria, and a burst of free radical formation occurs, conditions that favor the activation of the mitochondrial permeability transition pore. Here the authors demonstrate that a blocker of the mitochondrial permeability transition pore, the nonimmunosuppressive cyclosporin A analogue N-methyl-Val-4-cyclosporin A (10 mg/kg intraperitoneally), administered during reperfusion and at 24 hours of reperfusion, diminishes infarct size in a rat model of transient focal ischemia of 2 hours' duration. The mitochondrial permeability transition pore may be an important target for drugs against stroke.
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University Hospital, Sweden.
S
S
Matsumoto
H
H
Friberg
M
M
Ferrand-Drake
T
T
Wieloch
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002536:Cerebral Arteries / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003524:Cyclosporins / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
D003524:Cyclosporins; D004791:Enzyme Inhibitors