Dietary supplementation with α-tocopherol reduces neuroinflammation and neuronal degeneration in the rat brain after kainic acid-induced status epilepticus

Abstract

Vitamin E (as α-tocopherol, α-T) is proposed to alleviate glia-mediated inflammation in neurological diseases, but such a role in epilepsy is still elusive. This study investigated the effect of α-T supplementation on glial activation, neuronal cell death and oxidative stress of rat brain exposed to kainate-induced seizures. Animals were fed for 2 weeks with a α-T-enriched diet (estimated intake of 750 mg/kg/day) before undergoing status epilepticus. Compliance to supplementation was demonstrated by the remarkable increase in brain α-T. Four days after seizure, brain α-T returned to baseline and lipid peroxidation markers decreased as compared to non-supplemented rats. Status epilepticus induced a lower up-regulation of astrocytic and microglial antigens (GFAP and MHC II, respectively) and production of pro-inflammatory cytokines (IL-1β and TNF-α) in supplemented than in non-supplemented animals. This anti-inflammatory effect was associated with a lower neuronal cell death. In conclusion, α-T dietary supplementation prevents oxidative stress, neuroglial over-activation and cell death occurring after kainate-induced seizures. This evidence paves the way to an anti-inflammatory and neuroprotective role of α-T interventions in epilepsy.

Metabolomic screening of pre-diagnostic serum samples identifies association between α- and γ-tocopherols and glioblastoma risk

“…As shown in animal studies, tocopherols reduce neuro-inflammatory effects in relation to epilepsy [23]. The anti-inflammatory effects of tocopherols, especially γ-tocopherol, have also been documented in animal studies investigating asthma and allergy [24, 25] and in several clinical studies [26].…”

Antioxidants as a Preventive Treatment for Epileptic Process: A Review of the Current Status

“…Vitamin E type molecules are highly lipophilic. α-Tocopherol has been reported to prevent neurotoxicity and neurological symptoms in rat models of chemically-induced epilepsy [ 124 ]. Convulsive behaviour was attenuated in pentylenetetrazol-, methyl- malonate- and pilocarpine-induced seizures, where brain lipid peroxidation and nitrite content were lowered, while CAT and SOD activities were increased, with resulting lower hippocampal damage and increased survival [ 90 , 125 , 201 ].…”

“…Diverse experimental models show that preliminary injections of α-tocopherol reduce seizure induced oxygen and nitrogen free radicals generation on a time scale of minutes-to-hours [ 124 ]. Short-term dietary α-tocopherol supplementation reduces brain lipid peroxidation evenfour days after KA-induced seizures.…”

“…Together with a high consumption rate of brain α-tocopherol observed in supplemented rats after seizures, this finding indicates that conditions of oxidative stress initiated by SE persist long after the earliest post-ictal phases and that a-tocopherol can play a prolonged antioxidant effect after the triggering event. α-Tocopherol markedly reduces neuronal cell death after SE [ 124 ].…”

Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy

“…Compelling evidence demonstrates that compounds such as alpha-tocopherol, edaravone, alpha-asarone having antioxidant properties can reduce neuroinflammation and neuronal degeneration in various models of epilepsy (Betti et al, 2011;Miyamoto et al, 2008;Shin et al, 2014). Curcumin (diferuloyl methane) is a polyphenolic diketone found in Curcuma longa Linn.…”