Journal of Plastic, Reconstructive & Aesthetic Surgery
Delayed acetyl-l-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury☆
Section snippets
Materials and methods
All work performed in accordance with the terms of the Animal (Scientific Procedures) Act 1986 (project no. 70/4210) and the number of animals used was kept to a minimum.
Under halothane anaesthesia (May & Baker Ltd., UK) (2 ml/min in oxygen), five groups of young adult Sprague–Dawley rats (250–300 g body weight) underwent unilateral left sciatic nerve division at the upper border of quadratus femoris (n = 5 per group). To prevent spontaneous regeneration, both proximal and distal nerve stumps were
Results
No adverse reactions were observed during the study. Table 1 and Fig. 1 summarise the effect of delay between axotomy and start of ALCAR administration on the mean sensory neuron counts in axotomised L4 + L5 DRGs compared to contralateral non-operated controls. Two weeks after axotomy, the mean neuron count in the contralateral non-axotomised control DRGs of the sham-treated group was 32 199 (SD, 400). This was similar to the contralateral controls of all ALCAR-treated groups (one-way ANOVA, P =
Discussion
Our present study demonstrates that systemic administration of ALCAR eliminates axotomy-induced loss of primary sensory neurons when the start of ALCAR treatment is delayed for up to 24 h after axotomy. Quantification of neuronal counts was performed in combined L4 + L5 DRGs as these lumbar ganglia comprise 98% of the entire sciatic nerve pool.30 The time-point of 2 weeks post-axotomy was chosen because our previous studies have shown that at this time the neuronal loss becomes very highly
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2017, Journal of Chemical NeuroanatomyCitation Excerpt :However, the exact mechanism involved in the reduction of sensory neuron loss is still unclear. In particular, it performs this function by facilitating the transport of long chain free fatty acids through the mitochondrial inner membrane (Wilson et al., 2007). Additionally, it exhibits this neuroprotective effect by increasing the transportation and regeneration of acetyl groups, the activity of mitochondrial DNA and the binding of nerve growth factors (Hart et al., 2004).
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2017, Brazilian Journal of OtorhinolaryngologyCitation Excerpt :After injury, regeneration of the facial nerve is problematic. Nerve injury, such as lipid peroxidation of neurovascular cells, can lead to oxidative stress as a result of the production of free radicals.1,2 Various methods have been used to enhance peripheral nerve regeneration.3,4
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2014, Experimental NeurologyCitation Excerpt :Consistent with these central effects, systemic ALCAR administration reduced the loss of sensory neurons after sciatic nerve transection injury in rats, the effect persisting for up to two months following treatment (Hart et al., 2002). Moreover, a delay of administration up to 24 h after injury did not affect the efficacy of the drug in neuron rescue (Wilson et al., 2007). In addition to the neuroprotective effect, ALCAR also accelerates axon regeneration, demonstrated by increased number, diameter, and myelin thickness of regenerated axons (Wilson et al., 2007, 2009, 2010).
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2014, BiomaterialsThe effects of N-acetyl-cysteine and acetyl-l-carnitine on neural survival, neuroinflammation and regeneration following spinal cord injury
2014, NeuroscienceCitation Excerpt :NAC has been approved for clinical use for many years, being used as a mucolytic agent and for treatment of acetaminophen intoxication (Heard, 2008; Sadowska, 2012; Ziment, 1988). We have previously demonstrated that treatment with NAC and ALC can delay the degeneration of sensory neurons in the dorsal root ganglia (DRG) after peripheral nerve injury, and greatly reduce early retrograde death of spinal motorneurons after ventral root avulsion (Hart et al., 2002; Welin et al., 2009; Wilson et al., 2007; Zhang et al., 2005). In our recent short-term study we have shown that NAC and ALC also attenuate degeneration of spinal motoneurons after lumbar SCI, reduce the activity of microglia and macrophages and promote axonal sprouting in the injured segment of the cord (Karalija et al., 2012).
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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.