Potential of Khaya senegalensis to mitigate epileptogenesis and cognitive dysfunction on kainate-induced post-status epilepticus model

Abstract

Background and aim

To date, there is no treatment to prevent the development of temporal lobe epilepsy, the most common form of drug-resistant epilepsy. A recent study revealed the antiepileptic-like effect of the aqueous extract of Khaya senegalensis. Given the potential of this extract, the antiepileptogenic- and learning and memory-facilitating-like effects of the aqueous extract of Khaya senegalensis were assessed using the kainate-induced post-status epilepticus model.

Methods

Epilepsy was induced by injecting a single dose of kainate (12 mg/kg, i.p.) in rats. Animals that developed 2 hours of status-epilepticus were randomized and treated as follows: a negative control group received distilled water (10 ml/kg, p.o.); two positive control groups received sodium valproate (300 mg/kg, p.o.) or phenobarbital (20 mg/kg, p.o.); and three test groups received the extract (50, 100, 200 mg/kg, p.o.). A sham group was added and received distilled water (10 ml/kg, p.o.). All treatments were performed twice daily until the occurrence of the first spontaneous seizure (stage 4 or 5) in the negative control group, on day 14. After the completion of treatments, memory impairment was assessed using the T-maze. Two weeks following behavioral analysis, the rats that received the most effective dose of the extract on spontaneous recurrent were challenged with pentylenetetrazole (30 mg/kg, i.p.). This is to assess their susceptibility to generalized tonic-clonic seizures (stage 5). Rats were finally euthanized, and pro-inflammatory cytokines, or neurogenesis markers were quantified in the hippocampus.

Results

The extract of Khaya senegalensis significantly prevented spontaneous recurrent seizures on day 14. It also reduced cognitive decline. Furthermore, it significantly decreased pro-inflammatory cytokines levels and increased those of neurotrophic factors.

Conclusions

These findings thus suggest that the extract is endowed with antiepileptogenic- and learning and memory-enhancing-like effects. These effects are likely mediated by anti-inflammatory and neurotrophic pathways. This justifies, therefore, its use to treat empirically epilepsy.