Model-Dependent Attenuation of Seizures by Cinnabar

Epilepsy is one of the most prevalent and severe neurological disorders, and it is inadequately controlled with currently available medications. While cinnabar (mercury(II) sulfide)-a traditional Chinese medicine-has historical application in epilepsy treatment, its therapeutic efficacy and underlying mechanisms are unclear. In this study, we find that cinnabar exerts model-dependent antiseizure efficacy in mice. Specifically, it significantly attenuates acute seizures, enhances the termination of diazepam-resistant status epilepticus, and reduces spontaneous seizures in the kainic acid (KA)-induced seizure model. Conversely, no therapeutic effect was found in the maximal electroshock-, pentylenetetrazole-, or kindling-induced seizure model. Fiber photometry revealed that cinnabar normalizes KA-induced hippocampal neurotransmission imbalances by simultaneously decreasing glutamate hyperactivity and γ-aminobutyric acid hypoactivity. Furthermore, cinnabar has neuroprotective effects and alleviates comorbid anxiety-like behaviors, while showing no alterations in motor function. Our findings suggest cinnabar's potential as a therapeutic agent for seizure management, via a mechanism associated with the reversal of the hippocampal excitatory/inhibitory imbalance.