Myelination, axonal loss and Schwann cell characteristics in axonal polyneuropathy compared to controls

Abstract

Introduction Polyneuropathy is a debilitating condition characterized by distal sensory and motor deficits. Schwann cell dysfunction and axonal loss are integral factors in pathophysiology and disease progression of polyneuropathy. Aims The aim of this study was the assessment of Schwann cell characteristics, nerve fibers and myelination parameters in polyneuropathy patients compared to controls. Methods Nerve tissue was obtained from polyneuropathy patients (n = 10) undergoing diagnostic sural nerve biopsies. Biopsies of healthy peripheral nerves (n = 5) were harvested during elective sural nerve grafting for chronic peripheral nerve lesions. Exclusion criteria for the healthy control group were recent neurological trauma, diabetes, neurological and cardiovascular disease, as well as active malignancies and cytotoxic medication within the last 12 months. The over-all architecture of nerve sections and myelination parameters were histomorphometrically analyzed. Immunofluorescent imaging was used to evaluate Schwann cell phenotypes, senescence markers and myelination parameters. Results Histomorphometric analysis of nerve biopsies showed significant axonal loss in polyneuropathy patients compared to controls, which was in accordance with the neuropathological findings. Immunofluorescent staining of Schwann cells and myelin basic protein indicated a significant impairment of myelination and lower Schwann cell counts compared to controls. Phenotypic alterations and increased numbers of non-myelinating p75-positive Schwann cells were found in polyneuropathy patients. Discussion This study provided quantitative data of axonal loss, reduced myelination and Schwann cell dysfunction of polyneuropathy patients compared to neurologically healthy controls. Phenotypic alterations of Schwann cells were similar to those seen after peripheral nerve injury, highlighting the clinical relevance of Schwann cell dysfunction.

Surgically Induced Demyelination in Rat Sciatic Nerve

“…In comparison to the VEH and 4 d p-SNI rat groups, TEM data indicate atrophic axons, inter axonal space, and myelin loss in 10 d p-SNI rats. According to prior research, electronmicroscopic alterations in a rat's sciatic nerve following differential traction damage were described [40][41][42]. Significant changes in axonal intactness and repair of inter-axonal gaps were observed in the TF-treated p-SNI rats, supporting our neuropathological findings on demyelination followed by recovery and remyelination after TF therapy.…”

Chronic alcohol induced mechanical allodynia by promoting neuroinflammation: A mouse model of alcohol‐evoked neuropathic pain

“…See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Schwann-cell cytoplasm and macrophage (Bosch et al, 1978). The loss of Schwann cells represents a key point in the development of neuropathy symptoms, as Schwann cells actively participate in the development of neuropathic pain (de Logu et al, 2019;Placheta-Györi et al, 2021). In line with this evidence, our data showing a reduction of the protein expression of S100, a marker of Schwann cells, in sciatic nerve tissue in 2BC-N mice compared with 2BC mice indicates neuropathy that developed in these animals.…”

“…To examine whether the observed chronic ethanol-induced mechanical hypersensitivity is associated with the peripheral neuropathy, we assessed demyelination processes in the sciatic nerve represented by the loss of Schwan cells, frequently associated with the peripheral neuropathies (De Logu et al, 2019;Placheta-Györi et al, 2021). The 2BC-N group showed a significant (P = 0.0001; Because the activation of the immune system has been observed in the peripheral neuropathies, we also examine activation of the immune response in the spinal cord in the 2BC-N mice.…”

Pathways and Processes Underpinning Axonal Biology and Pathobiology

“…These PNS glial cells are critical for the proper function of the DRG neurons, and disease states such as diabetes have been shown to alter their function, resulting in neurodegeneration and pain. Indeed, evidence of mild axonal demyelination and remyelination is apparent even when the axon is normal, suggesting that Schwann cell abnormalities may be an early step in DPN pathology, and might be a primary cause of axonal damage (Malik et al, 2005;Gonçalves et al, 2018;Placheta-Györi et al, 2021). Experimental evidence supports a primary role for dysfunctional Schwann cells in the etiology of DPN.…”