Post-seizure α-tocopherol treatment decreases neuroinflammation and neuronal degeneration induced by status epilepticus in rat hippocampus.
Vitamin E (as α-tocopherol, α-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 α-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 α-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 α-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 α-T in kainic acid-induced epilepsy. Moreover, the findings show that post-seizure treatment with α-T provides an effective secondary prevention against post-seizure inflammation-induced brain damages and possibly against their epileptogenic effects.
Department of Earth, Life and Environmental Sciences, University of Urbino Carlo Bo, 61029, Urbino, Italy, patrizia.ambrogini@uniurb.it.
Patrizia
P
Ambrogini
Andrea
A
Minelli
Claudia
C
Galati
Michele
M
Betti
Davide
D
Lattanzi
Silvia
S
Ciffolilli
Marta
M
Piroddi
Francesco
F
Galli
Riccardo
R
Cuppini
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007608:Kainic Acid; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D024502:alpha-Tocopherol; D007608:Kainic Acid