AUTHOR=Tong Xiangzhen , Zhang Zizhu , Zhu Jianping , Li Shuji , Qu Shaogang , Qin Bing , Guo Yanwu , Chen Rongqing 

TITLE=A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.821917

DOI=10.3389/fneur.2022.821917

ISSN=1664-2295

ABSTRACT=Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors of epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics. In this study, we hypothesized that AEDs used to control acute SE might affect the feasibility for the chronic development of epileptogenesis after SE. So we sought to compare the epileptogenic effects of SE terminated by three AEDs, i.e., diazepam, midazolam and pentobarbital which are widely used first-line anti-SE AEDs. For this purpose, we used a mouse model of SE induced by intraperitoneal (i.p.) injection of LiCl-pilocarpine. The pilocarpine-induced SE was terminated with diazepam, midazolam or pentobarbital. Then we compared short-term and long-term effects of SE with different AED treatments by examining SE-associated mortality, behavioral spontaneous recurrent seizures (SRS), and using magnetic resonance imaging (MRI) and immunohistochemistry to evaluate pathological and cellular alterations of mice in the different treatment groups. We found that, while i.p. injections of diazepam (5 mg/kg), midazolam (10 mg/kg) and pentobarbital (37.5 mg/kg) were able to terminate acute pilocarpine-SE effectively, pentobarbital treatment showed less neuroprotective action against lethality in the short phase following SE. Long-term evaluation following SE revealed that SE treated by midazolam resulted in relatively less behavioral SRS, less hippocampal atrophy and milder neuronal loss and gliosis. Our data reveal an obvious advantage of midazolam vs. diazepam or pentobarbital in protecting brain from epileptogenesis. Therefore, if midazolam provides as strong action to quench SE as other AEDs in clinics, midazolam should be the first choice of anti-SE AEDs as it provides additional benefit against epileptogenesis.