title: Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion.
abstract: Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.
authors: Department of Neurology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors: Fang-Fang
authors: FF
authors: Liu
authors: Department of Respiratory Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors: Chao-Ying
authors: CY
authors: Liu
authors: Department of Pediatrics, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors: Xiao-Ping
authors: XP
authors: Li
authors: Department of Neurology, Affiliated Hospital of Yanbian University, Yanbian, Jilin Province, China.
authors: Sheng-Zhe
authors: SZ
authors: Zheng
authors: Department of Hepatic-Biliary-Pancreatic Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors: Qing-Quan
authors: QQ
authors: Li
authors: Department of Neurology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors: Qun
authors: Q
authors: Liu
authors: Department of Respiratory Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors: Lei
authors: L
authors: Song
keywords: NSFC grant; SMAD3; apoptosis; brain injury; cerebral ischemia; inflammation; nerve regeneration; neural regeneration; neuroprotection; transforming growth factor β1