Effects of adrenal dysfunction and high-dose adrenocorticotropic hormone on NMDA-induced spasm seizures in young Wistar rats

Infantile spasms (IS) is a devastating epilepsy syndrome treated with adrenocorticotropic hormone (ACTH). To demonstrate the effects of adrenal dysfunction, adrenalectomy (ADX) and N-methyl-D-aspartate (NMDA)-induced rat model studies of IS were performed. The latency of the seizure in the ADX group decreased and the severity of seizures increased significantly. Hippocampal corticotropin-releasing hormone (CRH) mRNA was overexpressed in ADX rats. After ACTH administration, the latency increased and the severity of seizures decreased significantly. ADX increased seizure susceptibility of the rats to NMDA. Pretreatment with a single high dose of ACTH caused an obvious reduction in susceptibility to NMDA-induced seizures and suppressed CRH mRNA expression. These findings are especially useful for IS patients with adrenal diseases and worthy of further clinical study. (C) 2012 Elsevier B.V. All rights reserved.