Anticonvulsant and Neuroprotective Effects of Dexmedetomidine on Pilocarpine-Induced Status Epilepticus in Rats Using a Metabolomics Approach

BACKGROUND: Status epilepticus (SE) is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment and early neuroprotection. Dexmedetomidine (DEX) is mainly used for its sedative, analgesic, anxiolytic, and neuroprotective effects with light respiratory depression. The purpose of this study was to comprehensively analyze the metabolic events associated with anticonvulsion and neuroprotection of DEX on pilocarpine-induced status epilepticus rats by LC-MS/MS-based on metabolomics methods combined with histopathology. MATERIAL/METHODS: In this research, rats were divided into 3 groups: a normal group, an SE group, and an SE+DEX group. Hippocampus of rats from each group were collected for further LC-MS/MS-based metabolomic analysis. We collected brains for HE staining and Nissl staining. Multivariate analysis and KEGG enrichment analysis were performed. RESULTS: Results of metabolic profiles of the hippocampus tissues of rats proved that dexmedetomidine relieved rats suffering from the status epilepticus by restoring the damaged neuromodulatory metabolism and neurotransmitters, reducing the disturbance in energy, improving oxidative stress, and alleviating nucleic acid metabolism and amino acid in pilocarpine-induced status epilepticus rats. CONCLUSIONS: This integral metabolomics research provides an extremely effective method to access the therapeutic effects of DEX. This research will further development of new treats for status epilepticus and provide new insights into the anticonvulsive and neuroprotective effects of DEX on status epilepticus.