Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment.
Peripheral nerve trauma remains a major cause of morbidity, largely due to the death of approximately 40% of innervating sensory neurons, and to slow regeneration after repair. Acetyl-L-carnitine (ALCAR) is a physiological peptide that virtually eliminates sensory neuronal death, and may improve regeneration after primary nerve repair. This study determines the effect of ALCAR upon regeneration after secondary nerve repair, thereby isolating its effect upon neuronal regenerative capacity. Two months after unilateral sciatic nerve division 1 cm nerve graft repairs were performed (n=5), and treatment with 50 mg/kg/day ALCAR was commenced for 6 weeks until harvest. Regeneration area and distance were determined by quantitative immunohistochemistry. ALCAR treatment significant increased immunostaining for both nerve fibres (total area 264% increase, P<0.001; percentage area 229% increase, P<0.001), and Schwann cells (total area 111% increase, P<0.05; percentage area 86% increase, P<0.05), when compared to no treatment. Regeneration into the distal stump was greatly enhanced (total area 2,242% increase, P=0.008; percentage area 3,034% increase, P=0.008). ALCAR significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma, in addition to its known neuroprotective effects.
McKay Hart
Andrew
A
Blond-McIndoe Centre, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
Wiberg
Mikael
M
Terenghi
Giorgio
G
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects; D019771:Axotomy; D002452:Cell Count; D004195:Disease Models, Animal; D007120:Immunochemistry; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects* / Q000254:growth & development / Q000293:injuries; D013997:Time Factors
D016900:Neurofilament Proteins; D018697:Nootropic Agents; D009418:S100 Proteins; D000108:Acetylcarnitine