Protection against ischemic brain damage in rats by immunophilin ligand GPI-1046.
To determine the effect of immunophilin ligand GPI-1046 on ischemic brain injury, 90 min of transient middle cerebral artery occlusion (MCAO) was carried out in rat brains. In contrast to cases treated with vehicle, the infarct volume was reduced greatly and rotamase activity was inhibited significantly at 24 hr of reperfusion by treatment with GPI-1046. Immunoreactivity and the number of cells stained positively for FKBP12, FKBP52, caspase-8, cytochrome c, and caspase-3 were also reduced markedly in the brain after GPI-1046 treatment. The present results suggest that GPI-1046 significantly decreased infarct volume and provided neuroprotective effect on rats after transient focal cerebral ischemia by inhibiting the increase of rotamase activity and of the number of FKBP12-, FKBP52-, caspase-8-, cytochrome c-, and caspase-3-positive cells in the ischemic area.
Li
Feng
F
Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan. lifeng@cc.okayama-u.ac.jp
Omori
Nobuhiko
N
Hayashi
Takeshi
T
Jin
Guang
G
Sato
Keiko
K
Nagano
Isao
I
Shoji
Mikio
M
Abe
Koji
K
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology; D020169:Caspases / Q000187:drug effects; D045304:Cytochromes c / Q000187:drug effects; D020104:Immunophilins / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D022021:Tacrolimus Binding Proteins / Q000187:drug effects*
C104949:GPI 1046; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D045304:Cytochromes c; D020169:Caspases; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins