Melatonin alleviates retinal injury induced by vigabatrin and partially enhances its antiepileptic effects

Structural optimization and combinational use with additive agents might help expand the clinical use of vigabatrin (VGB). Aiming to investigate the combinational effect of melatonin (MLT) on the antiepileptic action and retinal damage of VGB, a rat epilepsy model was induced by intraperitoneal injection of kainic acid (KA) and evaluated via both Racine grading and electroencephalogram (EEG). MLT (5, 10, 20 mg/kg) and VGB (50, 150 mg/kg) were administered intragastrically for 4 weeks, alone or together. The behavioral performance was measured during the remission of seizures via a series of tasks including the open field test (OFT), beam walking test (BW), Y-maze, and novel object recognition test (NOR). The morphological changes of the hippocampus and retina were observed using HE, Nissl, or immunofluorescence staining. Furthermore, the expression of proteins associated with synaptic plasticity and the Wnt/β-catenin/GSK3β signaling pathway were assessed. The results showed that intraperitoneal injection of KA could induce not only seizure, but also long-term behavioral impairments of sense, motion, and learning and memory in rats. Moreover, VGB could alleviate the neuroinflammation and balance the expression of synaptic plasticity and Wnt/β-catenin/GSK3β pathway proteins of epileptic rats. A combination of MLT couldn't enhance the effect of VGB in prolonging the seizure latency but presented an additive effect in alleviating the seizures grading V and improving the behavioral performance in the BW. Crucially, the combination of MLT considerably reduced the retinal cell damage caused by VGB. These results suggested that MLT could be a beneficial combination for VGB in the treatment of epilepsy, which might provide fresh insight into the clinical application of VGB and MLT.

Antiepileptic; Epilepsy; Melatonin; Retinal damage; Synaptic plasticity; Vigabatrin.