Diazepam administration after prolonged status epilepticus reduces neurodegeneration in the amygdala but not in the hippocampus during epileptogenesis
An episode of status epilepticus (SE), if left untreated, can lead to death, or brain damage with long-term neurological consequences, including the development of epilepsy. The most common first-line treatment of SE is administration of benzodiazepines (BZs). However, the efficacy of BZs in terminating seizures is reduced with time after the onset of SE; this is accompanied by a reduced efficacy in protecting the hippocampus against neuronal damage, and is associated with impaired function and internalization of hippocampal GABAA receptors. In the present study, using Fluoro-Jade C staining, we found that administration of diazepam to rats at 3 h after the onset of kainic acid-induced SE, at a dose sufficient to terminate SE, had no protective effect on the hippocampus, but produced a significant reduction in neuronal degeneration in the amygdala, piriform cortex, and endopiriform nucleus, examined on days 7–9 after SE. Thus, in contrast to the hippocampus, the amygdala and other limbic structures are responsive to neuroprotection by BZs after prolonged SE, suggesting that GABAA receptors are not significantly altered in these structures during SE.
KeywordsAmygdala Hippocampus Benzodiazepines Status epilepticus Neurodegeneration Epileptogenesis
This work was funded by the National Institutes of Health CounterACT Program through the National Institute of Neurological Disorders and Stroke (award # U01 NS058162-01). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the federal government. This work was also supported by the Defense Threat Reduction Agency-Joint Science and Technology Office, Medical S&T Division (grant 1.E0021_07_US_C).
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