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. 2008 Jul 19;24(3):143–149. doi: 10.1007/s12264-008-1108-0

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

Yan-Bo Zhang 1, Sheng-Xing Li 1, Xi-Ping Chen 1, Li Yang 1, Yun-Ge Zhang 1, Ran Liu 1, Lu-Yang Tao 1,✉
PMCID: PMC5552539  PMID: 18500386

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.

Keywords: autophagy, apoptosis, traumatic brain injury, LC3, Beclin1, neurodegeneration

Footnotes

The two authors contributed equally to this work.

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