Clinical studies have shown that individuals with spinal cord injury (SCI) are particularly susceptible to infectious diseases, resulting in a syndrome called SCI-induced immunodeficiency syndrome (SCI-IDS), which is the leading cause of death after SCI. It is believed that SCI-IDS is associated with exaggerated activation of sympathetic preganglionic neurons (SPNs). After SCI, disruption of bulbospinal projections from the medulla oblongata C1 neurons to the SPNs results in the loss of sympathetic inhibitory modulation from the brain and brainstem and the occurrence of abnormally high levels of spinal sympathetic reflexes (SSR), named sympathetic hyperreflexia. As the post-injury survival time lengthens, mass recruitment and anomalous sprouting of excitatory interneurons within the spinal cord result in increased SSR excitability, resulting in an excess sympathetic output that disrupts the immune response. Therefore, we first analyze the structural underpinnings of the spinal cord-sympathetic nervous system-immune system after SCI, then demonstrate the progress in highlighting mechanisms of SCI-IDS focusing on norepinephrine (NE)/Beta 2-adrenergic receptor (β2-AR) signal pathways, and summarize recent preclinical studies examining potential means such as regulating SSR and inhibiting β2-AR signal pathways to improve immune function after SCI. Finally, we present research perspectives such as to promote the effective regeneration of C1 neurons to rebuild the connection of C1 neurons with SPNs, to regulate excitable or inhibitory interneurons, and specifically to target β2-AR signal pathways to re-establish neuroimmune balance. These will help us design effective strategies to reverse post-SCI sympathetic hyperreflexia and improve the overall quality of life for individuals with SCI.

中文翻译：

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脊髓损伤引起的免疫缺陷综合征（SCI-IDS）的主要机制：交感神经反射亢进

临床研究表明，脊髓损伤（SCI）个体特别容易感染传染病，导致一种称为SCI诱导的免疫缺陷综合征（SCI-IDS）的综合征，这是SCI后死亡的主要原因。据信 SCI-IDS 与交感神经节前神经元 (SPN) 的过度激活有关。SCI 后，从延髓 C1 神经元到 SPN 的球脊髓投射中断，导致大脑和脑干的交感抑制调节丧失，并出现异常高水平的脊髓交感反射 (SSR)，称为交感反射亢进。随着损伤后生存时间的延长，脊髓内兴奋性中间神经元的大量募集和异常萌芽导致 SSR 兴奋性增加，导致交感神经输出过多，破坏免疫反应。因此，我们首先分析 SCI 后脊髓-交感神经系统-免疫系统的结构基础，然后展示以去甲肾上腺素 (NE)/β2-肾上腺素能受体 (β2-AR) 为重点的 SCI-IDS 机制的进展。信号通路，并总结了最近的临床前研究，探讨了调节 SSR 和抑制 β2-AR 信号通路等潜在手段来改善 SCI 后的免疫功能。最后，我们提出了促进C1神经元有效再生、重建C1神经元与SPN的连接、调节兴奋性或抑制性中间神经元、特别是靶向β2-AR信号通路以重建神经免疫平衡等研究观点。这些将帮助我们设计有效的策略来逆转 SCI 后交感神经反射亢进并改善 SCI 患者的整体生活质量。