American Journal of Biochemistry and Biotechnology

Immunohistochemical Detection of Apoptosis-Related Proteins in Gerbil Hippocampus Transient Cerebral Ischemia: Neuroprotective Effect of Pitavastatin

Toshiki Himeda, Natsumi Hayakawa, Hiroko Tounai, Aki Tanaka, Hiroyuki Kato and Tsutomu Araki

DOI : 10.3844/ajbbsp.2005.212.225

American Journal of Biochemistry and Biotechnology

Volume 1, Issue 4

Pages 212-225

Abstract

Delayed and selective neuronal damage was caused in the CA1 sector of hippocampus following 5 min of transient cerebral ischemia in gerbils. We investigated the immunohistochemical alterations of apoptosis-related proteins such as bcl-2α, bcl-xs/l, bax, cytochrome c, and active caspase 3 and TUNEL staining in the hippocampus at 1 and 5 hr and 1, 2, 5 and 14 days after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the alterations of apoptosis-related proteins and TUNEL staining in the hippocampus after cerebral ischemia. The alterations of apoptosis-related proteins in the hippocampal CA1 sector were more pronounced than the changes of hippocampal CA3 sector and dentate gyrus after cerebral ischemia. The alterations of apoptosis-related proteins in the hippocampal CA1 sector after cerebral ischemia preceded the neuronal damage in this region. Furthermore, the study with TUNEL staining showed that a marked increase of TUNEL-positive nuclei was evident only in the hippocampal CA1 sector 5 days after cerebral ischemia. Our immunohistochemical study also showed that pitavastatin prevented the alterations of apoptosis-related proteins and the increase of TUNEL-positive nuclei in the hippocampal CA1 sector 5 days after cerebral ischemia. The present study indicates that transient cerebral ischemia in gerbils causes the mitochondrial-dependent apoptosis in the hippocampal CA1 sector. Furthermore, our present study demonstrates that pitavastatin can prevent the alterations of apoptosis-related proteins and the increase of TUNEL-positive nuclei in the hippocampal CA1 sector after cerebral ischemia. Thus our study provides novel therapeutic strategies in clinical stroke.

Copyright

© 2005 Toshiki Himeda, Natsumi Hayakawa, Hiroko Tounai, Aki Tanaka, Hiroyuki Kato and Tsutomu Araki. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.