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Post-Ischemic Alterations in [3H]FK506 Binding in the Gerbil and Rat Brains

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurology, Tohoku University School of Medicine, Sendai, Japan

    T. Araki, H. Kato & Y. Itoyama

  2. Pharmacological Research Laboratory, Research Laboratories, Tokyo Tanabe Co. Ltd., Tokyo, Japan

    T. Araki & K. Shuto

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  1. T. Araki
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  2. H. Kato
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  3. K. Shuto
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  4. Y. Itoyama
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Araki, T., Kato, H., Shuto, K. et al. Post-Ischemic Alterations in [3H]FK506 Binding in the Gerbil and Rat Brains. Metab Brain Dis 13, 9–19 (1998). https://doi.org/10.1023/A:1020622827351

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