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

作　　者：Zhi-Sheng Wu Wen-Li Huang Shu-Jie Gong 

机构地区：[1]Department of Neurology,The First Affiliated Hospital of Quanzhou,Fujian Medical University,Quanzhou,Fujian 362000,China.

出　　处：《Chinese Medical Journal》2019年第21期2628-2635,共8页中华医学杂志（英文版）

摘　　要：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 oneway 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.Conc

关 键 词：EPILEPSY Status epilepticus BRAIN injuries Oxidative stress Neurons Inflammation 

分 类 号：R73[医药卫生—肿瘤]