Gastrodin alleviates seizure severity and neuronal excitotoxicities in the rat lithium-pilocarpine model of temporal lobe epilepsy via enhancing GABAergic transmission

Temporal lobe epilepsy remains one of the most drug-resistant focal epilepsy, leading to enormous healthcare burden. Among traditional herb medicine, some ingredients have the potential to treat seizure and alleviate the neuronal excitoxicity. The dried rhizome of Gastrodia elata Blume has been used to treat convulsive disorder, dizziness, dementia and migraine in eastern Asia. To determine whether gastrodin, an active ingredient of Gastrodia elata Blume, can reduce lithium-pilocarpine induced seizure severity and neuronal excitotoxicity and explore the underlying mechanism. We divided the Sprague-Dawley rats into an experimental group (gastrodin group) and a control group (Dimethyl sulfoxide, vehicle group) and performed the behavioral analysis and electroencephalography to determine the effect of gastrodin on the seizure severity induced by lithium-pilocarpine injection. Nissl-stained histopathology elucidated the degree of rat hippocampal neuronal damage as markers of acute and subacute neuronal excitotoxicity. Besides, the Western blotting of dissected hippocampus was carried out to demonstrate the protein expression involving GABAergic transmission and metabolic pathway. Gastrodin reduced the acute seizure severity in lithium-pilocarpine-induced seizure model. In electroencephalography recording, gastrodin exerted inhibitory action on epileptiform discharge. Compared with control group, gastrodin exhibited neuroprotective effect against seizure related hippocampal neuronal damage at acute and subacute stages. The Western blotting showed that gastrodin reversed the degradation of GABAA receptor after pilocarpine-induced seizures. In the experimental seizure model, gastrodin showed anti-seizure and neuroprotective abilities. Enhancing the expression of GABAA receptor plays an important role in its antiepileptic mechanism. The results offer a new insight of developing new antiepileptic drugs from traditional Chinese medicine.