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@ARTICLE{Kohle:1018545,
author = {Kohle, Felix and Ackfeld, Robin and Klein, Ines and
Svačina, Martin K. R. and Schneider, Christian and van
Beers, Tim and Grandoch, Andrea and Fink, Gereon R. and
Lehmann, Helmar C. and Barham, Mohammed},
title = {2,4-{D}initrophenol does not exert neuro-regenerative
potential in experimental autoimmune neuritis},
journal = {Neuroscience letters},
volume = {814},
issn = {0304-3940},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2023-04873},
pages = {137456 -},
year = {2023},
abstract = {Objective: We evaluated the potential neuro-regenerative
effects of the mitochondrial uncoupler 2,4-Dinitrophenol in
experimental autoimmune neuritis, an animal model for an
acute autoimmune neuropathy.Methods: Experimental autoimmune
neuritis was induced in Lewis rats. Different concentrations
of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg)
were applied during the recovery phase of the neuritis (at
days 18, 22 and 26) and compared to the vehicle. Any effects
were assessed through functional, electrophysiological, and
morphological analysis via electron microscopy of all groups
at day 30. Additional immune-histochemical analysis of
inflammation markers and remyelination of the sciatic nerves
were performed for the dosage of 1 mg/kg and
control.Results: No enhancement of functional or
electrophysiological recovery was observed in all
2,4-Dinitrophenol-treated groups. Cellular inflammation
markers of T cells (CD3+) were comparable to control, and an
increase of macrophages (IbA1+) invasion in the sciatic
nerves was observed. Treatment with 2,4-Dinitrophenol
reduced axonal swelling in myelinated and unmyelinated
fibers with an increased production of brain-derived
neurotrophic factor.Conclusion: Our findings do not support
the hypothesis that repurposing of the mitochondrial
uncoupler 2,4-Dinitrophenol exerts functionally relevant
neuro-regenerative effects in autoimmune neuritis.Keywords:
Autoimmune neuropathy; Brain-derived neurotrophic factor;
Drug repurposing; Guillain-Barré syndrome; Mitochondrial
uncoupler; Neuroregeneration.},
cin = {INM-3},
ddc = {610},
cid = {I:(DE-Juel1)INM-3-20090406},
pnm = {5251 - Multilevel Brain Organization and Variability
(POF4-525)},
pid = {G:(DE-HGF)POF4-5251},
typ = {PUB:(DE-HGF)16},
pubmed = {37648059},
UT = {WOS:001069379900001},
doi = {10.1016/j.neulet.2023.137456},
url = {https://juser.fz-juelich.de/record/1018545},
}