Nerve conductions studies in experimental models of autoimmune neuritis: A meta-analysis and guideline

Kohle, Felix; Sprenger, Alina; Klein, Ines; Fink, Gereon R.; Lehmann, Helmar C.

doi:10.1016/j.jneuroim.2020.577470

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…To calculate the NCV, the distance between both electrodes was divided by the difference of the latency; 10 F-waves’ persistence and minimum latencies were evoked by stimulating the electrode in the popliteal fossa and recorded for the right hind-paw. 22 Study report is based on the ‘Checklist for performance and reporting NCS in rats’ by Kohle et al 23 Proposed normative values based on meta-analyses by Kohle et al are as follows: NCV 47.24 m/s (43.65–50.84); CMAP sciatic notch 12.16 mV (9.72–14.60); CMAP ankle 17.41 mV (11.87–22.95).…”

Section: Methodsmentioning

confidence: 99%

Dose-dependent immunomodulatory effects of bortezomib in experimental autoimmune neuritis

Klimas

Sgodzai

Motte

et al. 2021

Brain Communications

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Proteasome inhibition with bortezomib has been reported to exert an immunomodulatory action in chronic autoimmune neuropathies. However, bortezomib used for the treatment of multiple myeloma induces a painful toxic polyneuropathy at a higher concentration. Therefore, we addressed this controversial effect and evaluated the neurotoxic and immunomodulatory mode of action of bortezomib in experimental autoimmune neuritis. Bortezomib-induced neuropathy was investigated in Lewis rats using the von Frey-Hair test, electrophysiological, qPCR, and histological analyses of the sciatic nerve as well as dorsal root ganglia outgrowth studies. The immunomodulatory potential of bortezomib was characterized in Lewis rats after experimental autoimmune neuritis induction with P253-78 peptide. Clinical, electrophysiological, histological evaluation, von Frey-Hair test, flow cytometric, and mRNA analyses were used to unravel the underlying mechanisms. We defined the toxic concentration of 0.2 mg/kg bortezomib applied intraperitoneally at days 0, 4, 8, and 12. This dosage induces a painful toxic neuropathy but preserves axonal regeneration in vitro. Bortezomib at a concentration of 0.05 mg/kg significantly ameliorated experimental autoimmune neuritis symptoms, improved experimental autoimmune neuritis-induced hyperalgesia and nerve conduction studies, and reduced immune cell infiltration. Furthermore, proteasome inhibition induced a transcriptional downregulation of Nfkb in the sciatic nerve, while its inhibitor Ikba (also known as Nfkbia) was upregulated. Histological analyses of bone marrow tissue revealed a compensatory increase of CD138+ plasma cells. Our data suggest that low dose bortezomib (0.05 mg/kg intraperitoneally) has an immunomodulatory effect in the context of experimental autoimmune neuritis through proteasome inhibition and downregulation of NFKB. Higher bortezomib concentrations (0.2 mg/kg intraperitoneally) induce sensory neuropathy; however, the regeneration potential remains unaffected. Our data empathizes, that bortezomib may serve as an attractive treatment option for inflammatory neuropathies in lower concentrations.

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Section: Methodsmentioning

confidence: 99%

Dose-dependent immunomodulatory effects of bortezomib in experimental autoimmune neuritis

Klimas

Sgodzai

Motte

et al. 2021

Brain Communications

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“…Nerve conduction studies (NCS) were performed before the immunisation at day 0, day 18 (maximum of the disease course) and day 30 (at the end of the recovery period), before the animals were killed. We followed the checklist for NCS as published [ 22 ] (Additional file 1 : Material S1).…”

Section: Methodsmentioning

confidence: 99%

Kinesin-5 inhibition improves neural regeneration in experimental autoimmune neuritis

Kohle,

Ackfeld,

Hommen

et al. 2023

J Neuroinflammation

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Background Autoimmune neuropathies can result in long-term disability and incomplete recovery, despite adequate first-line therapy. Kinesin-5 inhibition was shown to accelerate neurite outgrowth in different preclinical studies. Here, we evaluated the potential neuro-regenerative effects of the small molecule kinesin-5 inhibitor monastrol in a rodent model of acute autoimmune neuropathies, experimental autoimmune neuritis. Methods Experimental autoimmune neuritis was induced in Lewis rats with the neurogenic P2-peptide. At the beginning of the recovery phase at day 18, the animals were treated with 1 mg/kg monastrol or sham and observed until day 30 post-immunisation. Electrophysiological and histological analysis for markers of inflammation and remyelination of the sciatic nerve were performed. Neuromuscular junctions of the tibialis anterior muscles were analysed for reinnervation. We further treated human induced pluripotent stem cells-derived secondary motor neurons with monastrol in different concentrations and performed a neurite outgrowth assay. Results Treatment with monastrol enhanced functional and histological recovery in experimental autoimmune neuritis. Motor nerve conduction velocity at day 30 in the treated animals was comparable to pre-neuritis values. Monastrol-treated animals showed partially reinnervated or intact neuromuscular junctions. A significant and dose-dependent accelerated neurite outgrowth was observed after kinesin-5 inhibition as a possible mode of action. Conclusion Pharmacological kinesin-5 inhibition improves the functional outcome in experimental autoimmune neuritis through accelerated motor neurite outgrowth and histological recovery. This approach could be of interest to improve the outcome of autoimmune neuropathy patients.

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2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis

Kohle,

Ackfeld,

Klein

et al. 2023

Neuroscience Letters

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Nerve conductions studies in experimental models of autoimmune neuritis: A meta-analysis and guideline

Cited by 4 publications

References 41 publications

Dose-dependent immunomodulatory effects of bortezomib in experimental autoimmune neuritis

Dose-dependent immunomodulatory effects of bortezomib in experimental autoimmune neuritis

Kinesin-5 inhibition improves neural regeneration in experimental autoimmune neuritis

2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis

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