Edaravone dexborneol exerts anti-epileptic effects on rodent temporal lobe epilepsy by promoting NMDAR deactivation and inhibiting oxidative stress

Abstract

Background

Disease-modifying treatments with anti-epileptic effects are currently unavailable and urgently required for temporal lobe epilepsy (TLE). Combined therapy targeting multiple mechanisms may offer a promising anti-epileptic strategy, given the complex processes underlying epileptogenesis.

Purpose

This study evaluates the effects of Edaravone Dexbroneol, a combination of Edaravone and Dexborneol in 4:1, on rat and mouse TLE models and an in vitro epileptiform activity model.

Methods

The Pilocarpine-induced rat TLE model and the Kainic acid-induced mouse TLE model were used to assess the in vivo effect of Edaravone and/or Dexbornel. Primary neurons were utilized to evaluate the in vitro effect of drugs using calcium imaging, electrophysiological and biochemical analyses, as well as RNA sequencing.

Results

Treatment of Edaravone Dexbornel during the latent period significantly alleviated epileptic seizures in rodents, mitigated cognitive impairment, and inhibited neuronal loss and astrocytic activation. In vitro, Edaravone Dexborneol inhibited the action potentials and protected primary hippocampal neurons from Mg²⁺-free-induced neurite injury. All these effects were significantly more pronounced in the group treated with the Edaravone Dexborneol mixture compared to either drug used individually. Furthermore, Edaravone can significantly inhibit Mg²⁺-free-induced calcium oscillations in primary neurons, probably by promoting the deactivation of NMDA receptors. RNA sequencing and RT-PCR analysis revealed that synergetic regulation of lipid metabolism, oxidative stress, apoptosis, and calcium signaling probably underlay the neuroprotective effect of Edaravone Dexbornel on epileptic neurons.

Conclusion

Edaravone Dexborneol exhibits antiepileptic effects and may fill the gap in disease-modifying treatments for TLE.