Unbiased analysis of the dorsal root ganglion after peripheral nerve injury: no neuronal loss, no gliosis, but satellite glial cell plasticity

Schulte, Annemarie; Lohner, Hannah; Degenbeck, Johannes; Segebarth, Dennis; Rittner, Heike L.; Blum, Robert; Aue, Annemarie

doi:10.1097/j.pain.0000000000002758

Cited by 17 publications

(22 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Avulsed DRG were collected during nerve reconstruction surgery and analyzed by immunohistochemistry, large-scale tile microscopy, human DRG-adapted deep learning-based algorithms, 23 and new concepts for quantitative assessment of the different cell types close to the neuron-satellite-glia unit. 11 Our data document that patients suffering from plexus injury can be categorized into two groups: patients with total loss or patients with complete preservation of the multicellular DRG entity.…”

Section: Introductionmentioning

confidence: 79%

“…Pixel resolution was 0.454 μm. Objective bioimage analysis was performed using deepflash2 31 as described recently, 11, 23 with some modifications. Image feature annotation was performed on 10 exemplary sections marked by neurofilament (NF) by three experts using the QuPath software (Bankhead et al 2017, RRID:SCR_018257).…”

Section: Methodsmentioning

confidence: 99%

“…These injuries lead to adaptions in the DRG cell composition and cellular plasticity in the whole DRG. [11][12][13][14] Loss of sensory neurons seems to depend on the severity of injury. 14 Satellite glial cells (SGC), a cell type that forms a functional entity with the sensory neuron soma, react within hours after nerve injury and contribute to pain by enhancing neuronal excitability.…”

Section: Introductionmentioning

confidence: 99%

“…15 Typical plasticity responses of SGCs, e.g. after ventral root avulsion or spared nerve injury, 11, 16 include an increased expression of the glial fibrillary acidic protein (GFAP) or apolipoprotein J (APOJ). 13, 15, 17 Furthermore, macrophages become activated, invade, or proliferate locally in the DRG close to the neuron-SGC entity.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human dorsal root ganglia after plexus injury: either preservation or loss of the multicellular unit

Schulte

Degenbeck

Aue

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Objective: Plexus injury results in lifelong suffering of flaccid paralysis, sensory loss, and intractable pain. For this clinical problem, regenerative medicine concepts, such as cell replacement for restoring dorsal root ganglion (DRG) function, set high expectations. However, it is completely unclear which DRG cell types are affected by plexus injury. Methods: We investigated the cellular composition of human DRG in a clinically characterized cohort of patients with plexus injury. Avulsed DRG of 13 patients were collected during reconstructive nerve surgery. Then, we analyzed the cellular composition of the DRG with a human-adapted objective deep learning-based analysis of large-scale microscopy images. Results: Surprisingly, in about half of the patients, the injury-affected DRG no longer contained DRG cells. The complete entity of neurons, satellite glial cells, and microglia was lost and replaced by mesodermal/connective tissue. In the other half of patients, the cellular entity of the DRG was well preserved. We found no loss of neurons, no gliosis, and macrophages close to single sensory neuron/satellite glial cell entities. Patients with "neuronal preservation" had less pain than patients with "neuronal loss". Interpretation: The findings classify plexus injury patients in two categories: type I (neuronal preservation) and type II (neuronal loss). We call for early, post-accidental interventions to protect the entire DRG and improved MRI diagnostics to detect "neuronal loss". Regenerative medicine to restore DRG function will need at least two translational directions: reafferentation of existing DRG units for type I injuries; or replacement of the entire DRG structure for type II patients.

show abstract

Section: Introductionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human dorsal root ganglia after plexus injury: either preservation or loss of the multicellular unit

Schulte

Degenbeck

Aue

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…SGCs, which share biological properties with astrocytes in the CNS ( Ceruti, 2021 ), are activated during neuroinflammation in the PNS ( Matsuda et al, 2019 ). Previous studies have reported that nerve injury or persistent inflammation not only causes neuronal changes leading to peripheral sensitization but also results in activation of SGCs in the DRG ( Blum et al, 2014 ; Schulte et al, 2022 ). It is generally known that SGCs overactivation contributes to peripheral neuroinflammation and pathological pain via SGC-neuron interactions.…”

Section: Discussionmentioning

confidence: 99%

Satellite glial cells drive the transition from acute to chronic pain in a rat model of hyperalgesic priming

Yi²,

Xi³

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Chronic pain is one of the most common clinical syndromes affecting patients’ quality of life. Regulating the transition from acute to chronic pain is a novel therapeutic strategy for chronic pain that presents a major clinical challenge. However, the mechanism underlying pain transitions remains poorly understood. A rat hyperalgesic priming (HP) model, which mimics pain transition, was established decades ago. Here, this HP model and RNA sequencing (RNA-seq) were used to study the potential role of neuroinflammation in pain transition. In this study, HP model rats developed prolonged hyperalgesia in the hind paw after carrageenan (Car) and PGE2 injection, accompanied by obvious satellite glial cell (SGC) activation in the dorsal root ganglion (DRG), as indicated by upregulation of GFAP. RNA-Seq identified a total of differentially expressed genes in the ipsilateral DRG in HP model rats. The expression of several representative genes was confirmed by real-time quantitative PCR (qPCR). Functional analysis of the differentially expressed genes indicated that genes related to the inflammatory and neuroinflammatory response showed the most significant changes in expression. We further found that the expression of the chemokine CXCL1 was significantly upregulated in the rat DRG. Pharmacological blockade of CXCL1 reduced protein kinase C epsilon overproduction as well as hyperalgesia in HP rats but did not prevent the upregulation of GFAP in the DRG. These results reveal that neuroinflammatory responses are involved in pain transition and may be the source of chronic pain. The chemokine CXCL1 in the DRG is a pivotal contributor to chronic pain and pain transition in HP model rats. Thus, our study provides a putative novel target for the development of effective therapeutics to prevent pain transition.

show abstract

Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia

Zhu,

Zheng,

Gong

et al. 2024

Mol Neurobiol

View full text Add to dashboard Cite

Unbiased analysis of the dorsal root ganglion after peripheral nerve injury: no neuronal loss, no gliosis, but satellite glial cell plasticity

Abstract: Supplemental Digital Content is Available in the Text.Deep learning-based analysis of large-scale bioimages of the dorsal root ganglion after nerve injury reveals satellite glial cell plasticity but no loss of sensory neurons.

Cited by 17 publications

References 68 publications

Human dorsal root ganglia after plexus injury: either preservation or loss of the multicellular unit

Human dorsal root ganglia after plexus injury: either preservation or loss of the multicellular unit

Satellite glial cells drive the transition from acute to chronic pain in a rat model of hyperalgesic priming

Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia

Contact Info

Product

Resources

About