背景:创伤性脑损伤(TBI)后,海马区中枢神经系统出现失衡,导致苔藓细胞纤维的增殖,导致膜放电异常。此外,细胞神经递质分泌的破坏会导致创伤后癫痫。大量的实验和临床资料表明,食欲素系统在海马中枢神经系统中起调节作用,但具体的调节作用尚不清楚。因此,需要对其相关性进行进一步的实验评估。
目的:本研究旨在研究食欲素受体激动剂(OXA)对控制性皮质撞击(CCI)小鼠癫痫发作阈值和强度的影响,并了解食欲素系统在创伤后癫痫(PTE)中的作用。
方法:将体重18-22g的C57BL/6雄性小鼠随机分为三组:假,CCI和CCI+OXA。三组小鼠依次构建模型,植入电极,并建立了药物输送套管。经过30天的康复,Sham组和CCI组通过给药套管注射生理盐水,而CCI+OXA组注射OXA。随后,所有小鼠每30分钟接受电刺激,共15次.癫痫易感性,持续时间,强度,并观察到认知变化。同时,免疫荧光法检测各组海马GABA能神经元的表达水平及变化。
结果:将OXA注入海马CA1可降低创伤后癫痫发作的阈值,延长出院后的持续时间,延长癫痫发作持续时间,降低认知能力,并加剧海马区GABA能神经元的丢失。
结论:根据结果,我们可以发现,在海马CA1区注射OXA拮抗剂可以治疗或预防创伤后癫痫的发生和进展。
BACKGROUND: 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.
OBJECTIVE: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.