Cardarin Effect on the Formation of Histopathological and Behavioral Abnormalities in the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Epilepsy is a severe neuropsychological disease accompaniedby the development of spontaneous recurrent seizures (SRS) and associatedbehavioral disorders that are difficult to treat. In recent years, theneuroprotective properties of agonists of peroxisome proliferator-activatedreceptors (PPAR α, β/δ, γ), nuclear transcription factors involvedin the regulation of lipid and carbohydrate metabolism, as well asinflammatory signaling pathways involved in the pathogenesis ofepilepsy, have been actively investigated. The neuroprotective propertiesof PPARγ agonists have been repeatedly described in models of epilepsy;the effects of PPARβ/δ agonists in these models have not been sufficiently investigated.The aim of this work was to study the effects of administering thePPARβ/δ agonist cardarin (GW501516) on the formation of histopathologicaland behavioral abnormalities in the lithium-pilocarpine model oftemporal lobe epilepsy (TLE). The lithium-pilocarpine model is oneof the best experimental models of chronic temporal lobe epilepsy.In this study, epilepsy was induced by administration of pilocarpineto male Wistar rats at the age of 7 weeks, one day after LiCl injection. Cardarin(2.5 mg/kg) was administered daily for 7 days after pilocarpine,with the first injection one day after pilocarpine injection. Behavioraltesting was performed 2–3 months after induction of the model in thefollowing tests: Open Field Test, Social Interaction, Novel ObjectsExploration, Y-Maze Spontaneous Alternation and Morris Water Maze.Brain sampling for histological studies (assessment of neuronaldeath, Nissl staining) was performed after the end of behavioraltesting, 95 days after TLE induction. It was shown that untreatedrats with TLE exhibited significant hippocampal neuron death andbehavioral impairment: increased motor activity, anxiety, memorydisorders, research and communicative behavior. Cardarin did notaffect the survival rate of hippocampal neurons, but reduced themanifestation of almost all the above-mentioned behavioral disorders,except for hyperactivity. Thus, this study demonstrated the promisinguse of PPARβ/δ agonists to attenuate the development of behavioraldisorders characteristic of epilepsy.