الفهرس 
Literature ReviewOnly 14 pages are availabe for public view
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Abstract
Current anticonvulsants are chiefly aimed at suppressing neuronal hyperexcitability to prevent or control the incidence of seizures. However, the role of oxidative stress and inflammation processes in seizures led to the proposition that antioxidant compounds may be considered as promising candidates for limiting the progression of epilepsy. One of the most well-known anticonvulsant is phenytoin (PHT) that has many adverse effects including cognitive impairment. Enhancement of cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway is closely related to the pathogenesis of cognitive impairment and psychiatric disorders. Moreover, vascular endothelial growth factor (VEGF), an endothelial growth factor has a documented role in neurogenesis and neuronal survival and cognitive impairment. Alpha-tocopherol (α-Toc) and Coenzyme Q 10 (CoQ10) are powerful antioxidants, may be able to preserve neuronal tissue and circumvent neurological deficits. The current study is divided into two sections. The first section aimed to determine if CoQ10 (100 mg/kg; p.o.) and/or α-Toc (100 mg/kg; p.o.) once daily for 14 consecutive days have a neuroprotective effects in rats against the observed oxidative stress and inflammation during seizures induced by single dose of 90 mg/kg; i.p. of pentylenetetrazole (PTZ) in rats, and to study their interactions with the conventional antiseizure drug PHT.
Overall, the data revealed that α-Toc and CoQ10 supplementation can ameliorate PTZ-induced seizures and recommended that nuclear factor erythroid 2–related factor 2 (Nrf2) and silencing information regulator 1 (SIRT1) signaling pathways may exemplify strategic molecular targets for seizure therapies. The results of the present study provide novel mechanistic insights regarding the protective effects of antioxidants in hippocampal and cortical tissues and suggest an efficient therapeutic strategy to attenuate seizures. Additionally, concurrent supplementation of CoQ10 and α-Toc may be more effective than either antioxidant alone in decreasing inflammation and oxidative stress in both cortical and hippocampal tissues. The aim of the second section of this study is to investigate the role of this antioxidants alone or combined in the preservation of brain tissue and the maintenance of memory formation in PHT-induced cognitive impairment in rats. The behavioral tests like novel object recognition (NOR) and elevated plus maze (EPM) were assessed after 14 days of treatment. Furthermore, VEGF, BDNF, TrkB, CREB gene expression levels in the hippocampus and prefrontal cortex were estimated using RT-PCR. Both antioxidants alone or combined with PHT showed improvement in behavioral tests compared to PHT. Moreover, our results demonstrate that they can improve cognitive impairment in PHT-treated rats, and the mechanism of treating is related to the VEGF, BDNF-TrkB-CREB signaling pathway. Our study indicated the usefulness α-Toc or CoQ10 as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.