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 structur...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 l 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.展开更多
It has been well established that the recovery ability of central nervous system （CNS） is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the i...It has been well established that the recovery ability of central nervous system （CNS） is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the investigation in this field becomes a ＂hot spot＂. Up to date, accumulating evidence supports the hypothesis that the failure of CNS neurons to regenerate is not due to their intrinsic inability to grow new axons, but due to their growth state and due to lack of a permissive growth environment. Therefore, any successful approaches to facilitate the regeneration of injured CNS axons will likely include multiple steps： keeping neurons alive in a certain growth-state, preventing the formation of a glial scar, overcoming inhibitory molecules present in the myelin debris, and giving direction to the growing axons. This brief review focused on the recent progress in the neuron regeneration of CNS in adult mammals.展开更多
基金This work was supported by the National Natural Science Foundation of China （No. 30571909） the Youth Teacher Foundation of Jiangsu Province （No. BU134701）+1 种基金 Medical Development Foundation of Soochow University （No. EE 134615） We also thank Jin-Sheng YANG for his help in polishing the English language.
文摘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 l 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.
基金supported by the National Natural Science Foundation of China(No.30571909,No.30872666)the Youth Teacher Foundation of Jiangsu Pro-vince(No.BU134701)China,and the Medical Development Foundation of Soochow University(No.EE134615)
文摘It has been well established that the recovery ability of central nervous system （CNS） is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the investigation in this field becomes a ＂hot spot＂. Up to date, accumulating evidence supports the hypothesis that the failure of CNS neurons to regenerate is not due to their intrinsic inability to grow new axons, but due to their growth state and due to lack of a permissive growth environment. Therefore, any successful approaches to facilitate the regeneration of injured CNS axons will likely include multiple steps： keeping neurons alive in a certain growth-state, preventing the formation of a glial scar, overcoming inhibitory molecules present in the myelin debris, and giving direction to the growing axons. This brief review focused on the recent progress in the neuron regeneration of CNS in adult mammals.
