中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (12): 1926-1927.doi: 10.4103/1673-5374.169619

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

条条大路通Salubrinal:内质网应激、神经保护与胶质瘢痕形成  

  

  • 收稿日期:2015-09-08 出版日期:2015-12-30 发布日期:2015-12-30
  • 基金资助:

    这项工作是由西班牙科学和创新部(SAF2009-11257),西班牙外经济与竞争力部(SAF2012-40126)以及FISCAM-卡斯蒂利亚 - 拉曼恰团体PI2008/19和PI2009/51资助

All roads go to Salubrinal: endoplasmic reticulum stress, neuroprotection and glial scar formation

Lorenzo Romero-Ramírez*, Manuel Nieto-Sampedro, M. Asunción Barreda-Manso   

  1. Hospital Nacional de Parapléjicos, SESCAM, Finca la Peraleda s/n, 45071 Toledo, Spain (Romero-Ramírez L, Nieto-Sampedro M, Barreda-Manso MA)
    Instituto Cajal, CSIC, Avda. Doctor Arce 37, 28002 Madrid, Spain
    (Nieto-Sampedro M, Barreda-Manso MA)
  • Received:2015-09-08 Online:2015-12-30 Published:2015-12-30
  • Contact: Lorenzo Romero-Ramírez, Ph.D.,lromeroramirez@sescam.jccm.es.
  • Supported by:

    This work was supported by grants from the Spanish Ministry of Science and Innovation (SAF2009-11257), the Spanish Ministry of Economy and Competitivity (SAF2012-40126) and grants PI2008/19 and PI2009/51 from the FISCAM-Castilla-La Mancha Community.

摘要:

脑血管病(如脑卒中)引发的中枢神经损伤或机械挫伤(如创伤性脑损伤),通过与血液物质和细胞的直接接触会破坏保护中枢神经系统微环境的血脑屏障。创伤和局部缺血造成的原发神经损伤会随着时间的延长而加剧,发生次级神经元丢失,反应性小胶质细胞和白细胞迁移至损伤位点可产生炎症介质,进而加剧细胞死亡。Salubrinal是一种具有细胞保护作用的小分子,会对内质网应激诱导的细胞死亡产生效果。Salubrinal的神经保护作用已在大鼠脑兴奋毒性神经损伤模型、睡眠呼吸暂停小鼠模型、脑局部缺血/再灌注损伤大鼠模型和创伤性脑损伤小鼠模型中有过报道。Salubrinal治疗通过内质网应激反应减少,降低病理条件下内质网蛋白,减少细胞死亡。此外,Salubrinal对少突胶质细胞也有保护作用,并能够减少脱髓鞘和改善脊髓损伤后小鼠的功能恢复。

Abstract:

CNS injuries caused by cerebrovascular pathologies (e.g. stroke) or mechanical contusions (e.g. traumatic brain injury), disrupt the blood-brain barrier (BBB) that protects the CNS microenvironment from a direct contact with blood substances and cells. The initial neural damage caused by the trauma and the ischemic process is extended in time by a secondary neuronal loss due to the reactive microglial cells and blood leukocytes that migrate to the lesion site and produce inflammatory mediators (e.g. reactive oxygen species) that increase cell death. The severity of the neural damage in patients will determine the extension of the short- and long-term physical, cognitive and emotional impairments associated with these pathologies.Glial cells (mainly astrocytes) and profibrotic mesenchymal cells (meningeal fibroblasts, perivascular fibroblasts and pericytes) react to the injury and migrate to the lesion site, secreting extracellular matrix proteins and inducing a new glia limitans called glial scar. This physical structure reduces the leakage of blood substances and the migration of blood cells to the lesion site, reducing cell death and facilitating the recovery of tissue homeostasis. However, the glial scar is one of the main obstacles to axonal regeneration after injury.