The Role of the Orexin System in Craniocerebral Trauma-Induced Epilepsy in Mice.

Abstract

Following traumatic brain injury (TBI), an imbalance arises in the central nervous system within the hippocampus region, resulting in the proliferation of mossy cell fibers, causing abnormal membrane discharge. Moreover, disruptions in cellular neurotransmitter secretion induce post-traumatic epilepsy. Extensive experimental and clinical data indicate that the orexin system plays a regulatory role in the hippocampal central nervous system, but the specific regulatory effects are unclear. Therefore, further experimental evaluation of its relevance is needed. This study aims to investigate the effects of orexin receptor agonists (OXA) on the seizure threshold and intensity in controlled cortical impact (CCI) mice, and to understand the role of the orexin system in post-traumatic epilepsy (PTE). Male C57BL/6 mice weighing 18-22 g were randomly divided into three groups: Sham, CCI, and CCI+OXA. The three groups of mice were sequentially constructed with models, implanted with electrodes, and established drug-delivery cannulas. After a 30-day recovery, the Sham and CCI groups were injected with physiological saline through the administration cannulas, while the CCI+OXA group was injected with OXA. Subsequently, all mice underwent electrical stimulation every 30 minutes for a total of 15 times. Epileptic susceptibility, duration, intensity, and cognitive changes were observed. Concurrently, the expression levels and changes of GABAergic neurons in the hippocampus of each group were examined by immunofluorescence. Injecting OXA into hippocampal CA1 reduces the threshold of post-traumatic seizures, prolongs the post-discharge duration, prolongs seizure duration, reduces cognitive ability, and exacerbates the loss of GABAergic neurons in the hippocampal region. Based on the results, we can find that injecting OXA antagonists into the CA1 region of the hippocampus can treat or prevent the occurrence and progression of post-traumatic epilepsy.