Delayed acetyl-L-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury.
Protection of sensory neurons after peripheral nerve injury is clinically crucial since inadequate sensory recovery is seriously affected by the death of up to 40% of sensory neurons. Immediate acetyl-L-carnitine (ALCAR) treatment eliminates this cell loss, but may not always be clinically feasible, hence we studied the effect of delaying the initiation of ALCAR treatment. Five groups of rats (n=5 per group) underwent unilateral sciatic nerve axotomy. ALCAR treatment (50 mg/kg/day) was initiated immediately, or after delays of 6 h, 24 h or 7 days after injury. A sham-treated group served as control. L4 and L5 dorsal root ganglia were harvested bilaterally 2 weeks after injury and stereological sensory neuron counts were obtained. Immediate sham treatment provided no neuroprotection (25% loss). Cell loss was eliminated when ALCAR was commenced within<or=24 h of axotomy. No statistically significant neuroprotective effect (18% loss) was evident compared to sham when ALCAR administration was initiated 7 days post-axotomy. When commenced within a clinically applicable time frame ALCAR treatment remains highly neuroprotective, potentially improving clinical outcome following peripheral nerve trauma.
Wilson
Andrew D H
AD
Blond McIndoe Research Laboratory, Plastic and Reconstructive Surgery Research, University of Manchester, Manchester, UK, and Department of Surgical and Perioperative Science, Section for Hand & Plastic Surgery, University Hospital, Umeå, Sweden.
Hart
Andrew
A
Brännström
Thomas
T
Wiberg
Mikael
M
Terenghi
Giorgio
G
D000108:Acetylcarnitine / Q000008:administration & dosage*; D000818:Animals; D019771:Axotomy / Q000379:methods; D002452:Cell Count; D005727:Ganglia, Spinal / Q000503:physiopathology / Q000601:surgery; D007274:Injections, Intraperitoneal; D008159:Lumbar Vertebrae; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries*; D013997:Time Factors
D018696:Neuroprotective Agents; D000108:Acetylcarnitine