Study Of The Relationship Between Status Epilepticus-Induced Hippocampal Neuronal Death In Rats And Change Of Glutamate Receptors MRNA Expression

Objective To examine hippocampal neuronal death induced by status epilepticus and to test the role of the change of glutamate receptor-1, glutamate receptor-2 mRNA expression in mechanisms of hippocampal neuronal death.Methods Seizures were induced in adult, male Sprague-Dawley rats (175~200g) by injection of KA (15mg/kg, i.p.). Animals were monitored behaviorally for seizures for 6h after injection. Only rats displaying status epilepticus, defined as continual seizures for at least Ih, were used in this study. Normal control group were induced in same rats as seizure group by injection of Saline (3ml/kg, i.p.). Then animals were sacrificed at 6h, 12h, 16h, 20h, 24h, and Iw after injection of KA or 24h, Iw after injection of Saline. Brains were removed and wrapped. Neuronal damage was evaluated with Nissl-stains. Glutamate receptor-1 and glutamate receptor-2 mRNA expression were assessed by in situ hybridization in order to examine the relationship glutamate receptor mRNA expression and the deladyed hippocampal neuronal death.Results Nissl-stained sections at the level of the hippocampus revealed some neuronal degeneration and loss in the CA1, CA3 pyramidal cell only at 24h after status epilepticus, rats showed moderate to severe neuronal loss in the CA1, CA3 pyramidal cell at 1 week after status epilepticus. There was no histological detectable degeneration in the granule cell layer of the dentate gyrus after status epilepticus. In situ hybridization showed status epilepticus induced down-regulation GluR2 (but not GluRl) mRNA in CA1, CA3 before neuronal degeneration (i.e. before 24h after injection of KA). The expression of GluRl and GluR2 mRNA was both decreased at 24h after injection of KA and unchanged in the dentate gyrus after status epilepticus.Conclusion Our study show KA-induced status epilepticus lead to selective and delayed hippocampal neuronal death. Down-regulateon of glutamate receptor 2 mRNA could lead to formation of GluR2-lacking, Ca2+-permeable AMPA receptors and increased toxicity of endogenous glutamate, which may be involved in the mechanisms of thedelayed neuronal death.