Liu Nai-Kui, Xu Xiao-Ming
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery & Goodman Campbell Brain and Spine, Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Neural Regen Res. 2012 Sep 15;7(26):2051-62. doi: 10.3969/j.issn.1673-5374.2012.26.007.
Acute spinal cord injury initiates a complex cascade of molecular events termed 'secondary injury', which leads to progressive degeneration ranging from early neuronal apoptosis at the lesion site to delayed degeneration of intact white matter tracts, and, ultimately, expansion of the initial injury. These secondary injury processes include, but are not limited to, inflammation, free radical-induced cell death, glutamate excitotoxicity, phospholipase A2 activation, and induction of extrinsic and intrinsic apoptotic pathways, which are important targets in developing neuroprotective strategies for treatment of spinal cord injury. Recently, a number of studies have shown promising results on neuroprotection and recovery of function in rodent models of spinal cord injury using treatments that target secondary injury processes including inflammation, phospholipase A2 activation, and manipulation of the PTEN-Akt/mTOR signaling pathway. The present review outlines our ongoing research on the molecular mechanisms of neuroprotection in experimental spinal cord injury and briefly summarizes our earlier findings on the therapeutic potential of pharmacological treatments in spinal cord injury.
急性脊髓损伤引发一系列复杂的分子事件,称为“继发性损伤”,这会导致从损伤部位早期神经元凋亡到完整白质束延迟变性的进行性退化,并最终导致初始损伤范围扩大。这些继发性损伤过程包括但不限于炎症、自由基诱导的细胞死亡、谷氨酸兴奋性毒性、磷脂酶A2激活以及外在和内在凋亡途径的诱导,这些都是开发脊髓损伤神经保护治疗策略的重要靶点。最近,一些研究表明,在啮齿动物脊髓损伤模型中,使用针对继发性损伤过程(包括炎症、磷脂酶A2激活以及PTEN-Akt/mTOR信号通路的调控)的治疗方法,在神经保护和功能恢复方面取得了有前景的结果。本综述概述了我们目前在实验性脊髓损伤神经保护分子机制方面的研究,并简要总结了我们早期关于脊髓损伤药物治疗潜在疗效的研究结果。