Mild Hypothermia Promotes Pericontusion Neuronal Sprouting via Suppressing Suppressor of Cytokine Signaling 3 Expression after Moderate Traumatic Brain Injury
Mild Hypothermia Promotes Pericontusion Neuronal Sprouting via Suppressing Suppressor of Cytokine Signaling 3 Expression after Moderate Traumatic Brain Injury
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轻度低温通过抑制中度创伤性脑损伤后细胞因子信号传导抑制剂 3 的表达促进挫伤周围神经元出芽
DOI：
10.1089/neu.2016.4759
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发表时间：
2017
影响因子：
4.2
通讯作者：
Jiang Ji-Yao
中科院分区：
文献类型：
--
作者：
Zhao Cheng-Cheng;Wang Chuan-Fang;Li Wei-Ping;Lin Yong;Tang Qi-Lin;Feng Jun-Feng;Mao Qing;Gao Guo-Yi;Jiang Ji-Yao
亚低温治疗是治疗创伤性脑损伤的候选方法。然而，亚低温在脑外伤后神经元萌发中的作用仍不清楚。采用大鼠液压冲击伤(FPI)模型，观察亚低温对大鼠脑损伤后周围区神经元萌发的影响。雄性SD大鼠于伤后7d处死，分别行亚低温(33℃)或常温(37℃)处理3 h。免疫荧光和Western印迹分析证实生长相关蛋白-43(GAP-43)表达增加证实了神经元的萌发。采用实时定量聚合酶链式反应(RT-PCR)技术检测神经突起生长抑制因子A(NogoA)、磷酸酶与张力蛋白同源基因(PTEN)、细胞因子信号转导抑制因子3(SOCS3)等基因的表达水平。结果表明，与常温颅脑损伤组相比，亚低温治疗后7d，同侧大脑皮质GAP-43的表达水平显著升高，而IL-6和SOCS3的表达水平显著降低。这些数据表明，创伤后亚低温促进了脑外伤后结缔组织周围神经元的萌发。此外，低温诱导神经元萌发的机制可能部分与SOCS3水平降低有关。
Mild therapeutic hypothermia is a candidate for the treatment of traumatic brain injury (TBI). However, the role of mild hypothermia in neuronal sprouting after TBI remains obscure. We used a fluid percussion injury (FPI) model to assess the effect of mild hypothermia on pericontusion neuronal sprouting after TBI in rats. Male Sprague–Dawley rats underwent FPI or sham surgery, followed by mild hypothermia treatment (33°C) or normothermia treatment (37°C) for 3 h. All the rats were euthanized at 7 days after FPI. Neuronal sprouting that was confirmed by an increase in growth associated protein-43 (GAP-43) expression was evaluated using immunofluorescence and Western blot assays. The expression levels of several intrinsic and extrinsic sprouting-associated genes such as neurite outgrowth inhibitor A (NogoA), phosphatase and tensin homolog (PTEN), and suppressor of cytokine signaling 3 (SOCS3) were analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Our results revealed that mild hypothermia significantly increased the expression level of GAP-43 and dramatically suppressed the expression level of interleukin-6 (IL-6) and SOCS3 at 7 days after FPI in the ipsilateral cortex compared with that of the normothermia TBI group. These data suggest that post-traumatic mild hypothermia promotes pericontusion neuronal sprouting after TBI. Moreover, the mechanism of hypothermia-induced neuronal sprouting might be partially associated with decreased levels of SOCS3.