Impact of epileptic seizures on developing brain: a study using forebrain-specific Cdk5 conditional knockout mice

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Neuronal migration disorders are often identified in patients with epilepsy refractory to medical treatment. The prolonged or repeated seizures are known to cause neuronal death; however, the mechanism remains to be elucidated. The objective of this study is to elucidate the impact of epileptic seizures on the developing brain using forebrain-specific Cdk5 knockout (Cdk5cKO) mice which show neuronal migration defects and seizures. The forebrain of the mice showed neurodegenerative changes accompanied by neuronal loss and microglial activation. Treatment with PPAR-gamma agonist pioglitazone ameliorated gliosis and neuronal loss in Cdk5cKO mice, suggesting that inflammation contributes to the pathogenesis of the seizure-induced neuronal death. This study may provide impetus for considering the development of anti-inflammatory therapies that can be used to avoid the progressive decline of neuronal function in patients with neuronal migration disorders and epilepsy.