Exploring the Anticonvulsant and Neuropreventive Effects of Ganoderma lucidum Extract in the Pentylenetetrazole-Kindling Model: Analysis of Cognitive Comorbidities Associated with Epilepsy.

Abstract

Oxidative stress associated with neuronal death resulting from excitotoxicity represents a key pathophysiological mechanism contributing to the genesis and progression of neurofunctional alterations in epilepsy. Here, we evaluated the neuroprotective properties of GLE (300 mg/kg; i.g.) in the PTZ-induced Kindling model. Four groups of male Wistar rats were randomly assigned: control, PTZ, GLE-300, and Diazepam, each consisting of 8 rats. During the kindling process, 11 injections of PTZ (35 mg/kg; i.p.) were given every 48 h (21 consecutive days) to create a model of epilepsy. The 5-stage Racine scale was used to assess the severity of seizures. Moris water maze, Y maze test and novel object recognition was used to determine cognitive comorbidities. An assessment of oxidative stress biomarkers in the hippocampus was performed. Histological evaluation was also performed to quantify neuronal death in CA1 and CA3 using nissl staining. Our results show that supplementing animals with GLE attenuates PTZ-induced cognitive impairment and improves memory and learning deficits. In addition, GLE attenuated seizure severity and oxidative stress by decreasing lipid peroxidation and nitric oxide levels, and increasing superoxide dismutase and catalase activities in the hippocampus. Histopathological analysis also confirmed these results. These results indicate that GLE supplementation has therapeutic impacts on cognitive comorbidities and decreases PTZ damage, which may be associated with reduced oxidative stress in the hippocampus.