Research Article Open Access

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

Toshiki Himeda1, Natsumi Hayakawa1, Hiroko Tounai1, Aki Tanaka2, Hiroyuki Kato2 and Tsutomu Araki2
  • 1 The University of Tokushima, Japan
  • 2 International University of Health and Welfare, Japan

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.

American Journal of Biochemistry and Biotechnology
Volume 1 No. 4, 2005, 212-225

DOI: https://doi.org/10.3844/ajbbsp.2005.212.225

Submitted On: 3 March 2006 Published On: 31 December 2005

How to Cite: Himeda, T., Hayakawa, N., Tounai, H., Tanaka, A., Kato, H. & Araki, T. (2005). Immunohistochemical Detection of Apoptosis-Related Proteins in Gerbil Hippocampus Transient Cerebral Ischemia: Neuroprotective Effect of Pitavastatin. American Journal of Biochemistry and Biotechnology, 1(4), 212-225. https://doi.org/10.3844/ajbbsp.2005.212.225

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Keywords

  • Apoptosis
  • Immunohistochemistry
  • TUNEL
  • Pitavastatin
  • Gerbil