BACKGROUND Plexus injury results in lifelong suffering from flaccid paralysis, sensory loss, and intractable pain. For this clinical problem, regenerative medicine concepts set high expectations. However, it is largely unknown how dorsal root ganglia (DRG) are affected by accidental deafferentation. METHODS Here, we phenotyped DRG of a clinically and MRI-characterised cohort of 13 patients with plexus injury. Avulsed DRG were collected during reconstructive nerve surgery. For control, we used DRG from forensic autopsy. The cellular composition of the DRG was analysed in histopathological slices with multicolour high-resolution immunohistochemistry, tile microscopy, and deep-learning-based bioimage analysis. We then sequenced the bulk RNA of corresponding DRG slices. RESULTS In about half of the patients we found loss of the typical DRG units consisting of neurones and satellite glial cells. The DRG cells were replaced by mesodermal/connective tissue. In the remaining patients, the cellular units were well preserved. Preoperative plexus MRI neurography was not able to distinguish the two types. Patients with 'neuronal preservation' had less maximum pain than patients with 'neuronal loss'. Arm function improved after nerve reconstruction, but severe pain persisted. Transcriptome analysis of preserved DRGs revealed expression of subtype-specific sensory neurone marker genes, but downregulation of neuronal attributes. Furthermore, they showed signs of ongoing inflammation and connective tissue remodelling. CONCLUSIONS Patients with plexus injury separate into two groups with either neuronal preservation or neuronal loss. The former could benefit from anti-inflammatory therapy. For the latter, studies should explore mechanisms of neuronal loss especially for regenerative approaches. CLINICAL TRIAL REGISTRATION DRKS00017266.

中文翻译：

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人背根神经节在臂丛神经损伤传入神经阻滞后保留或完全丢失。


背景 神经丛损伤导致终生遭受弛缓性麻痹、感觉丧失和顽固性疼痛。对于这个临床问题，再生医学概念设定了很高的期望。然而，目前尚不清楚背根神经节 （DRG） 如何受到意外传入神经阻滞的影响。方法 在这里，我们对 13 名神经丛损伤患者的临床和 MRI 特征队列的 DRG 进行了表型分析。在重建神经手术中收集撕脱的 DRG。对于对照，我们使用法医尸检的 DRG。使用多色高分辨率免疫组织化学、平铺显微镜和基于深度学习的生物图像分析在组织病理切片中分析 DRG 的细胞组成。然后我们对相应 DRG 切片的大量 RNA 进行了测序。结果在大约一半的患者中，我们发现由神经元和卫星神经胶质细胞组成的典型 DRG 单位丢失。DRG 细胞被中胚层/结缔组织取代。在其余患者中，细胞单位保存完好。术前神经丛 MRI 神经造影无法区分这两种类型。“神经元保留”患者的最大疼痛程度低于“神经元丢失”患者。神经重建后手臂功能改善，但剧烈疼痛持续存在。保留的 DRG 的转录组分析揭示了亚型特异性感觉神经元标志基因的表达，但神经元属性下调。此外，他们表现出持续炎症和结缔组织重塑的迹象。结论 神经丛损伤患者分为两组，神经元保留或神经元丢失。前者可以从抗炎疗法中受益。 对于后者，研究应探索神经元丢失的机制，尤其是对于再生方法。临床试验注册DRKS00017266。