Summary
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 ≤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.
Keywords
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References
- Trophism, tropism, and specificity in nerve regeneration.J Reconstr Microsurg. 1994; 10: 345-354
- Experimental nerve reconnection: importance of initial repair.Microsurgery. 1989; 10: 56-70
- Sensory recovery after hand replantation: a clinical, morphological and neurophysical study in humans.Scand J Plast Reconstr Surg Hand Surg. 2003; 37: 163-173
- The cellular and molecular basis of peripheral nerve regeneration.Mol Neurobiol. 1997; 14: 67-116
- Primary sensory neurons and satellite cells after peripheral axotomy in the adult rat: timecourse of cell death and elimination.Exp Brain Res. 2002; 142: 308-318
- Nerve growth factor binding in aged rat central nervous system: effect of acetyl-l-carnitine.J Neurosci Res. 1988; 20: 491-496
- Carnitine acyltransferase: a review of its biology, enzymology and bioorganic chemistry.Bioorg Chem. 1988; 16: 307-334
- The role of carnitine in intracellular metabolism.J Clin Chem Clin Biochem. 1990; 28: 297-301
- Protective actions of l-carnitine and acetyl-l-carnitine on the neurotoxicity evoked by mitochondrial uncoupling or inhibitors.Pharmacol Res. 1995; 32: 383-389
- Culture of dorsal root ganglion neurons from aged rats: effects of acetyl-l-carnitine and NGF.Int J Dev Neurosci. 1992; 10: 321-329
- Acetyl-l-carnitine enhances the response of PC12 cells to nerve growth factor.Brain Res Dev Brain Res. 1991; 59: 221-230
- Primary sensory neuronal rescue with systemic acetyl-l-carnitine following peripheral axotomy. A dose–response analysis.Br J Plast Surg. 2003; 56: 732-739
- Systemic acetyl-l-carnitine eliminates sensory neuronal loss after peripheral axotomy: a new clinical approach in the management of peripheral nerve trauma.Exp Brain Res. 2002; 145: 182-189
- Peripheral nerve regeneration and neurotrophic factors.J Anat. 1999; 194: 1-14
- Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy.AIDS. 23-7-2004; 18: 1549-1560
- Idiopathic facial paralysis: new therapeutic prospects with acetyl-l-carnitine.Int J Clin Pharmacol Res. 1992; 12: 299-304
- Long-term acetyl-l-carnitine treatment in Alzheimer's disease.Neurology. 1991; 41: 1726-1732
- Acetyl-l-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study.Drugs R D. 2002; 3: 223-231
- l-Acetylcarnitine in the treatment of patients with peripheral neuropathies.Clin Drug Invest. 1995; 10: 317-322
- l-Acetylcarnitine as a new therapeutic approach for peripheral neuropathies with pain.Int J Clin Pharmacol Res. 1995; 15: 9-15
- Pharmacokinetics of IV and oral acetyl-l-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type.Eur J Clin Pharmacol. 1992; 42: 89-93
- Operating on hand-injured patients within six hours – can it be done?.British Association of Plastic Surgeons, 2003 (Summer Meeting)
- Audit of emergency throughput in a regional plastic surgery unit.Ann R Coll Surg Engl. 1994; 76: 161-163
- Hand lacerations. An audit of clinical examination.J Hand Surg [Br]. 1998; 23: 482-484
- Frozen-section fluorescence microscopy and stereology in the quantification of neuronal death within dorsal root ganglia.J Mol Histol. 2004; 35: 565-580
- Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias.Trends Neurosci. 1999; 22: 51-61
- Design-based stereological methods for counting neurons.Prog Brain Res. 2002; 135: 43-51
- Some new, simple and efficient stereological methods and their use in pathological research and diagnosis.APMIS. 1988; 96: 379-394
- The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis.APMIS. 1988; 96: 857-881
- Sensory neurons of the rat sciatic nerve.Exp Neurol. 1991; 114: 82-103
- Neuronal loss in lumbar dorsal root ganglia after proximal compared to distal sciatic nerve resection: a quantitative study in the rat.Brain Res. 23-1-1989; 478: 193-195
- Calibration of methods for determining numbers of dorsal root ganglion cells.J Neurosci Methods. 1990; 35: 187-194
- High dose l-carnitine improves immunologic and metabolic parameters in AIDS patients.Immunopharmacol Immunotoxicol. 1993; 15: 1-12
- Tolerability and efficacy of l-acetylcarnitine in patients with peripheral neuropathies. A short-term, open multicentre study.Clin Drug Invest. 1998; 15: 73-79
- Glucose and leucine uptake in the hypoglossal nucleus after hypoglossal nerve transection with and without prevented regeneration in the Sprague–Dawley rat.Neurosci Lett. 6-6-1986; 67: 73-77
- Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress.Proc Natl Acad Sci U S A. 2002; 99: 1870-1875
- Acetyl-l-carnitine protects against amyloid-beta neurotoxicity: roles of oxidative buffering and ATP levels.Neurochem Res. 2002; 27: 501-505
- Protection from oxygen radical damage in human diploid fibroblasts by acetyl-l-carnitine.Dementia. 1992; 3: 58-60
- Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-l-carnitine treatment.Neurosci Lett. 16-12-2002; 334: 181-185
Article info
Publication history
Published online: July 24, 2006
Accepted:
April 20,
2006
Received:
January 10,
2006
Footnotes
☆This work has been presented as detailed below:
- Acetyl-l-carnitine eliminates sensory neuron loss after peripheral nerve injury: dose–response relationship and effect of delay in administration. Wilson ADH, Brannstrom T, Wiberg M, Terenghi G. Peripheral Nerve Society, Banff, Canada, 2003.
- Delayed acetyl-l-carnitine administration & neuronal survival after peripheral nerve injury. Mr ADH Wilson, Dr T Brannstrom, Prof M Wiberg, Prof G Terenghi. B.A.P.S. Summer Conference, Newport, July 2003.
Identification
Copyright
© 2006 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Inc. All rights reserved.
