Rufinamide Mitigates Seizures and Behavioural Deficits via BDNF/TrkB Modulation and Oxidative Stress Reduction in Pentylenetetrazole-Kindled Mice

Abstract

Background

Rufinamide (RUF) is a 3rd generation antiseizure medication (ASM) with a triazole ring that blocks voltage-gated sodium channels (VGSCs) and is most commonly used to treat Lennox–Gastaut syndrome. Thus, the present study examined the effect of RUF on EEG activity, behavioural testing, oxidative stress, and mRNA expression in PTZ-kindled mice.

Methods

Male BALB/c mice were administered rufinamide (30, 60, and 90 mg/kg) for 21 days along with 11 injections of PTZ (40 mg/kg) given every other day. EEG recordings were monitored and a series of behavioural tests after RUF treatment were done to assess the post-kindling associated anxiety and memory impairment. We also assessed the oxidative alterations, variation in real-time BDNF/TrkB mRNA expression as well as neuroinflammatory markers in isolated mice brains.

Results

Analysis of results showed that RUF at the dose of 90 mg/kg maximally suppressed the progression of full-bloom seizures and decreased cortical epileptic spike discharge. Moreover, RUF showed significant anxiolytic action and prevented PTZ-induced cognitive decline in a dose-dependent manner. Because of its anti-inflammatory and antioxidant properties, RUF decreased lipid peroxidation, AChE activity, raised glutathione and superoxide dismutase levels in the mice brain. RUF suppressed the PTZ-induced upregulation of BDNF/TrkB signalling and significantly reduced pro-inflammatory cytokines.

Conclusion

It is possible that the effects of RUF that have been seen are the consequence of decreased oxidative stress, BDNF/TrkB downregulation, and reduced expression of neuroinflammatory markers, which in turn reduce ictogenesis and improve the neuropsychiatric consequences associated with epilepsy.