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Effect of adenovirus-mediated overexpression of PTEN on brain oxidative damage and neuroinflammation in a rat kindling model of epilepsy

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Author:: No author available

Journal Title:: Chinese Medical Journal

Issue:: 21

DOI:: 10.1097/CM9.0000000000000496

Key Word:: Epilepsy;Status epilepticus;Brain injuries;Oxidative stress;Neurons;Inflammation

Abstract： Background:Epilepsy is a chronic and severe neurological disorder.Phosphatase and tensin homolog deleted on chromosome ten (PTEN)-deficient mice exhibit learning and memory deficits and spontaneous epilepsy.The aim of this study was to investigate the role of PTEN in brain oxidative damage and neuroinflammation in a rat model of epilepsy.Methods:An adenovirus (Ad)-PTEN vector was constructed,and status epilepticus (SE) was induced in 41 model rats using lithium chloride-pilocarpine.Thirty-six SE rats were then allocated into the Ad-PTEN,Ad-LacZ,and SE groups,those were administered intracerebroventricular injections of Ad-PTEN,Ad-enhanced green fluorescent protein,and phosphate buffer saline,respectively.The normal group was comprised of healthy Sprague-Dawley rats.Nissl staining was conducted to evaluate neuronal damage,and immunohistochemistry was conducted to observe the morphology of cells in the hippocampal CA1 region and the distribution of ionized calcium-binding adaptor molecule 1 (Iba1) and ED1 (rat homologue of human CD68).Levels of apoptosis-related proteins,inflammatory-related factors,and oxidative stress-related markers (reactive oxygen species [ROS],glutathione [GSH],superoxide dismutase [SOD],and malondialdehyde [MDA]) were measured.Comparisons between multiple groups were conducted using one-way analysis of variance (ANOVA),and pairwise comparisons after ANOVA were conducted using the Tukey multiple comparisons test.Results:After SE induction,PTEN expression in the rat brain exhibited a four-fold decrease (P =0.000) and the expression of both Iba1 and ED1 increased.Furthermore,significant neuronal loss,oxidative damage,and neuroinflammation were observed in the SE rat brain.After intracerebroventricular injection of Ad-PTEN,PTEN expression exhibited a three-fold increase (P=0.003),and the expression of both Iba1 and ED1 decreased.Additionally,neurons were restored and neuronal apoptosis was inhibited.Furthermore,ROS and MDA levels decreased,GSH level and SOD activity increased,and neuroinflammation was reduced.Conclusion:Our study demonstrated that brain oxidative damage and neuroinflammation in SE rats were ameliorated by intracerebroventricular injection of Ad-PTEN.

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