中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (8): 1260-1266.doi: 10.4103/1673-5374.189190

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

创伤性脑损伤半暗带内质网应激介导的细胞凋亡加重继发性脑损伤

  

  • 出版日期:2016-08-31 发布日期:2016-08-31
  • 基金资助:
    河北省自然科学基金项目(H2014206383),河北省高层次人才资助项目(A201401041)

Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury

Guo-zhu Sun1, *, Fen-fei Gao2, Zong-mao Zhao1, Hai Sun3, Wei Xu1, Li-wei Wu1, Yong-chang He1   

  1. 1 Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China 2 Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong Province, China 3 Division of Neurological Surgery, Barrow Neurological Institute, St Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
  • Online:2016-08-31 Published:2016-08-31
  • Contact: Guo-zhu Sun, M.D., Ph.D., sungzh705@163.com.
  • Supported by:
    This study was supported by the Natural Science Foundation of Hebei Province of China, No. H2014206383; and Foundation for High-Level Personnel Projects in Hebei Province of China, No. A201401041.

摘要:

神经细胞凋亡包括膜介导细胞凋亡、线粒体介导细胞凋亡和内质网介导细胞凋亡,在创伤性脑损伤半暗带研究中内质网介导的细胞凋亡通路鲜见报道,在创伤性半暗带内质网应激能否激活caspase-12介导的内质网凋亡通路尚不完全清楚。实验应用液压冲击法建立创伤性脑损伤大鼠模型,观察发现大鼠创伤半暗带中caspase-12和caspase-3蛋白以及内质网应激标志物葡萄糖调节蛋白在损伤后6h表达即增多,24h达到峰值,同时在创伤半暗带TUNEL阳性细胞亦达到高峰。提示创伤性脑损伤激活了半暗带caspase-12介导的内质网细胞凋亡通路,可介导继发性脑损伤。 

orcid: 0000-0001-6380-8793 (Guo-zhu Sun)

关键词: 神经再生, 内质网应激, 细胞凋亡, caspase-12, caspase-3, 创伤半暗带, 外伤性脑损伤

Abstract: Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated, mitochondrial, and endoplasmic reticulum stress pathways. Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury, and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra. Here, we established rat models of ?uid percussion-induced traumatic brain injury and found that protein expression of caspase-12, caspase-3 and the endoplasmic reticulum stress marker 78 kDa glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours. Furthermore, numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury. These fndings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra, and may play an important role in the pathophysiology of secondary brain injury.

Key words: nerve regeneration, endoplasmic reticulum stress, apoptosis, caspase-12, caspase-3, traumatic penumbra, traumatic brain injury; neural regeneration