c-Fos, N-methyl-D-aspartate receptor 2C, GABA-A-α1 immonoreactivity, seizure latency and neuronal injury following single or recurrent neonatal seizures in hippocampus of Wistar rat

Abstract

To evaluate the long-term effects of single or recurrent prolonged neonatal seizures on seizure threshold and neuronal activity in the brain, a novel "twist" seizure was induced by coupling early-life flurothyl-induced seizures with later exposure to pentylenetetrazol. The authors assigned six neonatal rats for each group: the single-seizure group (SS), the recurrent-seizure group (RS) and the control group. At postnatal day 46, seizure threshold was examined using pentylenetetrazol, and then the brain slices were evaluated with thionine staining, in situ end labeling and immunohistochemical studies. The Results showed that the rats in SS and RS groups all had reduced latencies to develop generalized tonic seizures induced by PTZ compared with controls (P < 0.01). Morphologic changes, cell loss and apoptotic cells were observed only in those of RS group. Significant fos and NR2C-immunoreactive positive cells were seen in hippocampus of rats in both SS and RS groups compared with controls (P < 0.01). A significant decrease in the number of GABA-A-α1 immunoreactive positive neurons was detected in hippocampus in rats of SS and RS groups compared with the controls (P < 0.01). We conclude that neonatal rats subjected to prolonged seizures have pronounced long-term effects on seizure threshold and neuronal neurophysiological activity in the brain. Obvious neuronal injury, however, was only seen in rat with recurrent-seizures. Subtle brain damage might occur in rats experiencing single prolonged neonatal seizures. © 2005 Elsevier Ireland Ltd. All rights reserved.