Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

• Published in: Neural regeneration research 2015-03, Vol.10 (3), p.438-444
• Main Authors: Liu, Fang-Fang, Liu, Chao-Ying, Li, Xiao-Ping, Zheng, Sheng-Zhe, Li, Qing-Quan, Liu, Qun, Song, Lei
• Format: Article
• Language: English
• Subjects: Alzheimer′s disease; Apoptosis; apparent diffusion coefficient; astrocytes; auranofin; average combined score; blood-nerve barrier; bone marrow mesenchymal stem cells; Brain; brain injury; Care and treatment; Carotid arteries; cell transplantation; Cerebral ischemia; cisplatin; cochlea; Control; dextromethorphan; differentiation; diffusion tensor imaging; electroacupuncture therapy; Evans blue tracer; fiber tractography; fractional anisotropy; Gene therapy; Genetic aspects; glaucoma; hypothermia; inflammation; intraocular pressure; Ischemia; JNK3; laser photocoagulation; lumbar puncture; magnetic guidance; magnetic resonance image; magnetic resonance imaging; microglia; mRNA水平; nanocarrier; nerve regeneration; neural degeneration; neural regeneration; neural stem cells; neurodegeneration; neuroinflammation; neuroprotection; notch signaling pathway; NSFC grant; ocular hypertension; ototoxicity; peripheral nerve injury; Physiological aspects; Polyclonal antibodies; polyethyleneimine-polyethylene glycol; PP2; proliferation; Proteins; real-time quantitative PCR; regeneration; retinal ganglion cell; rosiglitazone; sciatic nerve; Smad proteins; SMAD3; SMAD3基因; Smad蛋白; spinal cord; spinal cord injury; spinal cord transection; spiral ganglion cells; Src kinase; superparamagnetic iron oxide; survival curve; tamoxifen; transforming growth factor β1; trauma; Veins & arteries; western blot assay; X-linked inhibitor of apoptosis protein; 大脑; 大鼠模型; 神经保护作用; 缺血/再灌注损伤; 转化生长因子α
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.153693

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. Phos- phorylated 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 ne- crosis factor-a and interleukin-lβ 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-inflamma- tory and anti-apoptotic pathways.