Acetyl-l-carnitine increases nerve regeneration and target organ reinnervation – a morphological study

SummaryPeripheral nerve injury frequently results in functional morbidity since standard management fails to adequately address many of the neurobiological hurdles to optimal regeneration. Neuronal survival and regeneration are neurotrophin dependent and require increased aerobic capacity. Acetyl-l-carnitine (ALCAR) facilitates this need and prevents neuronal loss. ALCAR is clinically safe and is shown here to significantly improve nerve regeneration and target organ reinnervation.Two groups of five rats underwent sciatic nerve division followed by immediate repair. One group received parenteral ALCAR (50 mg/kg/day) from time of operation until termination at 12 weeks. A ‘sham treatment’ group received normal saline. A third group was left unoperated and did not receive any treatment.A segment of nerve was harvested between 5 mm proximal and 10 mm distal to the repair in operated groups, and at the corresponding level in the unoperated group. Mean axonal count in normal, non-axotomised nerve was 14,720 (SD 2378). That of the saline group (17,217 SD 1808) was not significantly different from normal nerve (P = 0.0985). Mean number of myelinated axons in the ALCAR group (24,460 SD 3750) was significantly greater than both sham group (P < 0.01) and normal nerve (P = 0.0012). Mean myelin thickness in the saline treated group (0.408 μm SD 0.067 μm) was less than normal nerve (0.770 μm SD 0.143 μm) (P < 0.001). Mean myelin thickness in the ALCAR group (0.627 μm SD 0.052 μm) was greater than the sham (saline) group (P < 0.01) and not statistically different from normal nerve (P = 0.07).ALCAR increased dermal PGP9.5 staining by 210% compared to sham treatment (P < 0.0001) and significantly reduced the mean percentage weight loss in gastrocnemius muscle (ALCAR group 0.203% vs. 0.312% in sham group P = 0.015).ALCAR not only increases the number of regenerating nerve fibres but also morphologically improves the quality of regeneration and target organ reinnervation. Adjuvant ALCAR treatment may improve both sensory and motor outcomes and merits further investigation.