PDF(Pubmed)
Abstract：
Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual\'s outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-κB dependent in VGluT2+ INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.
摘要：
脊髓损伤（SCI）是一种毁灭性的疾病，每年全球有250,000至500,000个新病例。呼吸道感染,例如，肺炎和流感是SCI后死亡的主要原因。不幸的是,对于改变的神经免疫交流如何影响个体感染的结果，人们了解甚少。在人类和啮齿动物中，SCI导致脊髓交感神经反射（SSR）回路的适应性不良变化，这对交感神经功能至关重要。免疫功能受损的原因可能与有害的神经炎症有关，有害于稳态神经元功能。异常可塑性，和超级电路。可溶性肿瘤坏死因子（sTNF）是一种促炎细胞因子，在SCI后在CNS中升高，并在损伤后几个月内保持升高。通过药理学减弱SCI后CNS中的sTNF，我们能够证明免疫功能得到改善。此外，当我们调查可能与神经免疫通讯改变有关的特定细胞群时,我们报道了兴奋性INs上过度的TNFR1活性会促进免疫功能障碍.此外，该观察结果在VGluT2+INs中是NF-kB依赖性的。我们的数据是中枢神经系统内目标的第一份报告，TNFR1有助于T9-SCI后SCI诱导的免疫功能障碍，是未来治疗的潜在途径。
