Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
World Neurosurg. 2019 Dec;132:138-147. doi: 10.1016/j.wneu.2019.08.108. Epub 2019 Aug 27.
The infliction of a traumatic spinal cord injury (SCI) propagates damage that occurs in 2 stages. The first phase of trauma develops from the initial mechanical insult. The second phase involves the degradation of nervous tissue but is likely not affected by the initial insult. Thus, therapeutic targets with a high specificity for these secondary injury processes have been of increasing interest. We reviewed the pathophysiologic cascades of inflammation after SCI and potential therapeutic targets.
The PubMed and EMBASE databases were queried using appropriate medical subject headings for studies involving tumor necrosis factor (TNF)-α), nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, and/or Fas ligand (FasL) targets. The relevant studies found were graded into 3 levels (i.e., A, B, C) according to the quality of evidence.
We have summarized the basis of the neurological damage for TNF-α, NF-κB, iNOS, IL-1β, and FasL after SCI. A total of 17 studies were rated, each of which had reported histological, biochemical, physiological, and behavioral outcomes according to the treatment that had focused on TNF-α, NF-κB, iNOS, IL-1β, and FasL.
The TNF-α, iNOS, NF-κB, IL-1β, and FasL will become active within minutes after SCI. The adverse effects from the activity of these receptors include inflammation and other important neurological damage. Each of these targets can be modulated by specific agents with differing degrees of efficacy according to the reported data.
外伤性脊髓损伤(SCI)的发生会引发两个阶段的损伤。创伤的第一个阶段是由最初的机械损伤引起的。第二个阶段涉及神经组织的退化,但可能不受初始损伤的影响。因此,针对这些继发性损伤过程的治疗靶点具有越来越高的特异性。我们回顾了 SCI 后炎症的病理生理级联反应和潜在的治疗靶点。
使用适当的医学主题词在 PubMed 和 EMBASE 数据库中查询涉及肿瘤坏死因子(TNF)-α)、核因子(NF)-κB、诱导型一氧化氮合酶(iNOS)、白细胞介素(IL)-1β和/或 Fas 配体(FasL)靶点的研究。根据证据质量,将找到的相关研究分为 3 个等级(即 A、B、C)。
我们总结了 TNF-α、NF-κB、iNOS、IL-1β和 FasL 在 SCI 后引起神经损伤的基础。共有 17 项研究被评为,每项研究根据针对 TNF-α、NF-κB、iNOS、IL-1β和 FasL 的治疗,报告了组织学、生化、生理和行为学结果。
TNF-α、iNOS、NF-κB、IL-1β和 FasL 在 SCI 后几分钟内就会变得活跃。这些受体的活性引起的不良反应包括炎症和其他重要的神经损伤。根据报告的数据,这些靶点中的每一个都可以通过特异性的、效力不同的药物进行调节。