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Local low dose curcumin treatment improves functional recovery and remyelination in a rat model of sciatic nerve crush through inhibition of oxidative stress
M. Caillaud, B. Chantemargue, L. Richard, L. Vignaud, F. Favreau, PA. Faye, P. Vignoles, F. Sturtz, P. Trouillas, JM. Vallat, A. Desmoulière, F. Billet,
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antioxidants pharmacology MeSH
- Crush Injuries drug therapy pathology physiopathology MeSH
- NF-E2-Related Factor 2 metabolism MeSH
- Muscle, Skeletal drug effects pathology physiopathology MeSH
- Cells, Cultured MeSH
- Curcumin pharmacology MeSH
- Random Allocation MeSH
- Neural Conduction drug effects MeSH
- Sciatic Nerve drug effects injuries pathology physiopathology MeSH
- Neuroprotective Agents pharmacology MeSH
- Recovery of Function drug effects physiology MeSH
- Oxidative Stress drug effects MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Sprague-Dawley MeSH
- Remyelination drug effects physiology MeSH
- Molecular Dynamics Simulation MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Traumatic injuries to peripheral nerves are frequent, however, specific pharmacological treatments are currently lacking. Curcumin has antioxidant, anti-inflammatory and neuroprotective properties but high oral doses are required for therapeutic use, particularly due to its low bioavailability. The aim of the present study was to investigate the effects of local and continuous treatment using low curcumin doses on functional recovery and nerve regeneration after rat sciatic nerve crush (SNC). Curcumin was administered by osmotic pumps with a catheter delivering the drug at the injury site (0.2 mg/day for 4 weeks). Functionally, early improvements in mechanical sensitivity, finger spacing of the injured paw, skilful walking and grip strength were observed in curcumin-treated animals. The curcumin treatment increased expression of compact myelin proteins (MPZ and PMP22), myelin sheath thickness and, correspondingly, increased motor and sensitive nerve conduction velocity. Microscopic analysis of gastrocnemius muscle indicated a curcumin-induced decrease in neurogenic lesions. Curcumin treatment reduced the production of reactive oxygen species (ROS) (which were notably produced by macrophages), lipid peroxidation and increased expression of transcription factor Nrf2. In silico analyses indicated that curcumin combines all the characteristics required to be an efficient lipid peroxidation inhibitor at the heart of biological membranes, hence protecting their degradation due to ROS. This antioxidant capacity is likely to contribute to the beneficial effects of curcumin after SNC injury. These results demonstrate that, when administrated locally, low doses of curcumin represent a promising therapy for peripheral nerve regeneration.
Department of Biochemistry University Hospital of Limoges Limoges France
RCPTM Department of Physical Chemistry Faculty of Sciences Palacký University Olomouc Czech Republic
UMR INSERM 1094 NET Faculties of Medicine and Pharmacy University of Limoges Limoges France
UMR INSERM 1248 IPPRITT Faculties of Medicine and Pharmacy University of Limoges Limoges France
References provided by Crossref.org
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