Abstract
Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy.
Highlights
Multiple conditions including head trauma, stroke and Alzheimer’s disease can trigger status epilepticus (SE)
We examined and quantified the occurrence of basal dendrites projecting into the dentate hilus from DCX + newly born neurons that incorporated into the SGZ and granule cell layer (GCL) area with one or more major dendrites projecting into the dentate molecular layer (i.e. from relatively mature DCX + newly born neurons, Fig. 5(D,E))
Because reelin is involved in the appropriate migration of DCX + newly born neurons into the SGZ-GCL area and reelin is derived from subclasses of interneurons, we evaluated the number of interneurons expressing reelin in dentate hilus (DH) (Fig. 5(F1–H2))
Summary
Multiple conditions including head trauma, stroke and Alzheimer’s disease can trigger status epilepticus (SE). An ideal neuroprotective strategy for SE should be capable of restraining glutamatergic and GABA-ergic neuron loss, oxidative stress, inflammation and aberrant neurogenesis. In this context, compounds and drugs having neuroprotective and/or antiepileptogenic properties are ideal for preventing SE-induced chronic hippocampal dysfunction typified by SRS, and cognitive and mood impairments. Using a well-established kainate model of SE, we examined the effects of RESV treatment commencing an hour after SE for easing glutamatergic and GABA-ergic neuron loss, oxidative stress, inflammation and abnormal neurogenesis in the hippocampus, using immunohistochemical, biochemical and molecular biological methods and stereological cell counts
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