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Autophagy is activated and might protect neurons from degeneration after traumatic brain injury

大鼠脑外伤后自噬被激活并在早期对受损神经元起保护作用

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Abstract

Objective

To investigate changes of autophagy after traumatic brain injury (TBI) and its possible role.

Methods

Rat TBI model was established by controlled cortical injury system. Autophagic double membrane structure was detected by transmission electronic microscope. Microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 were also used to investigate the activation of autophagy post-TBI. Double labeling with LC3 and caspase-3, or Beclin 1 and Fluoro-Jade, to show the relationship between autophagy and apoptosis or neuron degeneration after TBI.

Results

An increase of autophagic double membrane structure was observed in early stage (1 h), and the increase lasted for at least 32 d post-TBI. LC3 and Beclin 1 proteins also began to elevate at 1 h time point post-TBI in neurons, 3 d later in astrocytes, and peaked at about 8 d post-TBI. In both cell types, LC3 and Beclin 1 maintained at a high level until 32 d post-TBI. Most LC3 and Beclin 1 positive cells were near the side (including hippocampus), but not in the core of the injury. In addition, in the periphery of the injury site, not all caspase-3 positive (+) cells merged with LC3 (+) cells post-TBI; In hippocampal area, almost all Beclin 1 (+) neurons did not merge with Fluoro-Jade (+) neurons from 1 h to 48 h post-TBI.

Conclusion

Autophagy is activated and might protect neurons from degeneration at early stage post-TBI and play a continuous role afterwards in eliminating aberrant cell components.

摘要

目的

研究大鼠脑外伤后自噬是否被激活并探讨其在脑外伤后神经细胞损伤和修复中的作用。

方法

建立大鼠定量脑外伤模型,于脑外伤后不同时间点处死动物并取脑; 应用透射电镜检测脑组织自噬双层膜结构以及次级溶酶体的形成情况; 应用自噬标记抗体LC3B和Beclin-1对脑外伤后不同时间点的脑组织进行免疫荧光和Westernblot 检测; LC3 和caspase-3 或Beclin 1 和Fluoro-Jade 双标记检测。

结果

脑外伤后1 h 在损伤区周围即检测到双层膜结构,并且一直持续到脑外伤后32 天。脑外伤后1 h,脑组织中LC3 和Beclin-1 表达增加,损伤后3 天内阳性细胞以神经元为主,之后阳性胶质细胞增加,第8 天达到高峰,并可持续至脑外伤后32 天仍维持高表达。大多数阳性细胞分布在损伤区周围(包括海马)而不是损伤区。此外,脑外伤后24 小时以前,在损伤区周围不是所有的LC3 阳性细胞都与caspase-3 阳性细胞重叠。同样脑外伤后6 h 至48 h,Beclin 1 阳性海马神经元与Fluoro-Jade染色不重叠。

结论

脑外伤后自噬被激活,在损伤后早期保护损伤区周围神经细胞免于凋亡和退行性变,并对神经细胞损伤与修复发挥长期作用。

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Authors and Affiliations

  1. Institute of Forensic Medicine, Laboratory of Aging and Nerves Diseases, Soochow University, Suzhou, 215123, China

    Yan-Bo Zhang, Sheng-Xing Li, Xi-Ping Chen, Li Yang, Yun-Ge Zhang, Ran Liu & Lu-Yang Tao

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  1. Yan-Bo Zhang
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  2. Sheng-Xing Li
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  4. Li Yang
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  5. Yun-Ge Zhang
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  6. Ran Liu
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  7. Lu-Yang Tao
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Correspondence to Lu-Yang Tao.

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The two authors contributed equally to this work.

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Zhang, YB., Li, SX., Chen, XP. et al. Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci. Bull. 24, 143–149 (2008). https://doi.org/10.1007/s12264-008-1108-0

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  • DOI: https://doi.org/10.1007/s12264-008-1108-0

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