Inflammogenesis of Secondary Spinal Cord Injury.
Inflammogenesis of Secondary Spinal Cord Injury.
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DOI：
10.3389/fncel.2016.00098
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发表时间：
2016
影响因子：
5.3
通讯作者：
Eid AH
中科院分区：
文献类型：
--
作者：
Anwar MA;Al Shehabi TS;Eid AH
脊髓损伤（SCI）和脊髓梗死导致神经系统并发症，最终导致截瘫或四肢瘫痪。这些极度衰弱的状况是导致发病的主要原因。在过去的十年中，我们对脊髓损伤的理解确实有所增加，但仍然很不清楚。脊髓损伤由两个确定的阶段组成：最初的撞击导致原发性损伤，随后是由可能持续数年的不断发展的子阶段组成的延长的继发性损伤。导致这种情况的潜在病理生理机制是复杂的。脉管系统的紊乱是脊髓损伤的一个显著病理特征。特别是，脊髓损伤的一个重要组成部分是缺血再灌注损伤（IRI），它导致内皮功能障碍和血管通透性改变。事实上，与内皮细胞损伤和稳态衰竭一起，缺血再灌注损伤引发了由固有免疫细胞（小胶质细胞和星形胶质细胞）和浸润性白细胞（中性粒细胞和巨噬细胞）激活引起的全面炎症级联反应。这些炎症细胞释放神经毒素（促炎细胞因子和趋化因子、自由基、兴奋性毒性氨基酸、一氧化氮（NO）），所有这些都参与轴突和神经元的缺陷。因此，我们的综述考虑了SCI机制的最新进展，由此可以清楚地看出SCI是一种异质性疾病。因此，这导致了基于多靶点单药治疗或联合治疗的恢复性方法的证据。此外，从现有文献的评估来看，似乎迫切需要针对大量患者群体的多中心随机试验。这些临床研究将为对高危SCI患者进行分层，并选择合适的、最佳的治疗方案进行个性化治疗提供机会。
Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine.