Human dorsal root ganglia are either preserved or completely lost after deafferentation by brachial plexus injury

Abstract

BackgroundPlexus 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. MethodsHere, 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. ResultsIn 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. ConclusionsPatients 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 registrationDRKS00017266.