BDNF/Cyclin D1 Signaling System and Cognitive Performance After Perampanel and Lacosamide Treatment Singly or in Combination in an Experimental Model of Temporal Lobe Epilepsy

Epilepsy is a common brain function disorder. The present study aims to evaluate the long-term effect of perampanel (PRM) and lacosamide (LCM), administered singly in a high-dose or in a low-dose combination of both, on comorbid anxiety, cognitive impairment, BDNF, and Cyclin D1 hippocampal expression in an experimental model of temporal lobe epilepsy with lithium-pilocarpine. PRM (3 mg/kg, p.o.)/LCM (30 mg/kg, p.o.) or PRM+LCM (0.5 mg/kg + 3 mg/kg, p.o.) treatments were administered three hours after the lithium-pilocarpine-induced status epilepticus and continued for up to ten weeks in adult Wistar rats. Our study demonstrated that perampanel and lacosamide administered singly in high doses improved epilepsy-associated cognitive impairment through ameliorating anxiety and facilitating passive learning and memory, with spatial and recognition memory measured in the elevated plus maze, step-through, Y-maze, and object recognition tests, respectively. In addition, the combination of both drugs in low doses demonstrated similar anxiolytic and cognitive-improving effects compared to the singly administered drugs. Moreover, the three experimental groups enhanced the hippocampal expression of the neurotrophic factor BDNF and mitigated the increased levels of the apoptotic factor Cyclin D1. These beneficial effects could be essential mechanisms through which administered anticonvulsants preserve neuronal survival and homeostasis in the CNS and especially in the hippocampus.