Effect of Valproic Acid on Bcl-2, Bim, and Caspase-3 Expression in Rat Hippocampus after Kainic Acid-Induced Seizures

Kim, Meyung Kug; Kim, Kwang Soo; Kim, Min Jeong; Kim, Jong Kuk; Yoo, Bong Goo; Ahn, Ji Hyun; Chang, Hee Kyung

Abstract

PURPOSE
To investigate the regional and temporal patterns of Bcl-2, Bim, and caspase-3 expression in rat hippocampus after kainic acid (KA)-induced seizures, and to determine whether valproic acid (VA) has the neuroprotective effect on hippocampal apoptotic cell death.
METHODS
Thirty five male Sprague-Dawley rats were used. KA (20 mg/kg) was injected once intraperitoneally in the experimental group, and 15 rats were immediately treated with repeated subcutaneous injections of VA. The brain was extracted at 4, 24, and 72 hours after KA injection. Immunohistochemical staining was conducted to assess the degree of Bcl-2, Bim, and caspase-3 expression at each hippocampal region. To investigate the effect of VA on apoptotic cell death, the expression degrees of Bcl-2, Bim, and caspase-3 were compared.
RESULTS
Bcl-2 expression started to increase 4 hours after KA injection at CA3 and CA4 regions, and lasted up to 72 hours. Bim expression was increased at CA2 and CA3 regions 4 and 24 hours after KA injection. Caspase-3 expression was increased at all regions of hippocampus 4 hours after the injection, and lasted up to 72 hours. The expressions of Bcl-2, Bim, and caspase-3 were not different between KA-injected group and KA and VA-injected group.
CONCLUSION
Although the present study was unable to confirm the neuroprotective effect of VA on KA-induced apoptotic cell death, this study showed that KA-induced seizures increased the expression of Bcl-2, Bim, and caspase-3. These results suggest that apoptotic cell death mechanism, such as the activation of cell death-regulating proteins Bcl-2, Bim, and caspase-3, involves in the KA-induced neuronal death.