Post-ischemic alterations in [3H]FK506 binding in the gerbil and rat brains.
We investigated post-ischemic changes in FK506 binding protein (FKBP) in the brain after transient global ischemia in gerbils or transient focal ischemia in rats. [3H]FK506 was used to label FKBP as a immunophilin. In transient global ischemia, [3H]FK506 binding showed a transient reduction in the frontal cortex only 1 h after recirculation. In the striatum, the dorsolateral part exhibited a significant increase in [3H]FK506 binding 5, 24 and 48 h after ischemia. However, the ventromedial part showed a transient elevation in [3H]FK506 binding 24 h after ischemia. Thereafter, the ventromedial part showed no conspicuous change in [3H]FK506 binding up to 7 days after ischemia. The dorsolateral part also showed no significant change in [3H]FK506 binding 7 days after ischemia. In the hippocampus and thalamus, [3H]FK506 binding was unchanged in the stratum radiatum of the hippocampal CA1 sector, hippocampal CA3 sector, dentate gyrus and thalamus up to 7 days after ischemia. However, the stratum oriens of the hippocampal CA1 sector showed a significant reduction in [3H]FK506 binding 48 h and 7 days after ischemia. A histological study showed that transient cerebral ischemia caused a severe damage in the striatum and hippocampal CA1 sector. In a model of transient focal ischemia, a marked increase in [3H]FK506 binding was also found in the striatum and cerebral cortex where severe infarctions were observed. These results demonstrate that post-ischemic change in [3H]FK506 binding between the striatum and hippocampus may be produced by different mechanisms. Furthermore, our findings suggest that immunophilins may play some role in the pathogenesis of ischemic diseases.
Araki
T
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kato
H
H
Shuto
K
K
Itoyama
Y
Y
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005849:Gerbillinae; D006360:Heat-Shock Proteins / Q000032:analysis*; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus