Post-Seizure [alpha]-Tocopherol Treatment Decreases Neuroinflammation and Neuronal Degeneration Induced by Status Epilepticus in Rat Hippocampus

Issue Title: Unveiling the significance of lipid signaling in neurodegeneration and neuroprotection Vitamin E (as [alpha]-tocopherol, [alpha]-T) was shown to have beneficial effects in epilepsy, mainly ascribed to its antioxidant properties. Besides radical-induced neurotoxicity, neuroinflammation is also involved in the pathophysiology of epilepsy, since neuroglial activation and cytokine production exacerbate seizure-induced neurotoxicity and contribute to epileptogenesis. We previously showed that [alpha]-T oral supplementation before inducing status epilepticus, markedly reduces astrocytic and microglial activation, neuronal cell death and oxidative stress in the hippocampus, as observed 4 days after seizure. In order to evaluate the possibility that such a neuroprotective and anti-inflammatory effect may also provide a strategy for an acute intervention in epilepsy, in this study, seizures were induced by single intaperitoneal injection of kainic acid and, starting from 3 h after status epilepticus, rats were treated with an intraperitoneal bolus of [alpha]-T (250 mg/kg b.w.; once a day) for 4 days, that was the time after which morphological and biochemical analyses were performed on hippocampus. Post-seizure [alpha]-T administration significantly reduced astrocytosis and microglia activation, and decreased neuron degeneration and spine loss; these effects were associated with the presence of a lowered lipid peroxidation in hippocampus. These results confirm and further emphasize the anti-inflammatory and neuroprotective role of [alpha]-T in kainic acid-induced epilepsy. Moreover, the findings show that post-seizure treatment with [alpha]-T provides an effective secondary prevention against post-seizure inflammation-induced brain damages and possibly against their epileptogenic effects.[PUBLICATION ABSTRACT]