Acetyl-L-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury.
In the present study, we evaluated the therapeutic efficacy of acetyl-l-carnitine (ALC) administration on mitochondrial dysfunction following tenth thoracic level contusion spinal cord injury (SCI) in rats. Initial results from experiments in vitro with naïve mitochondria showed that, in the absence of pyruvate, ALC can be used as an alternative substrate for mitochondrial respiration. Additionally, when added in vitro to mitochondria isolated from 24 h injured cords, ALC restored respiration rates to normal levels. For administration studies in vivo, injured rats were given i.p. injections of saline (vehicle) or ALC (300 mg/kg) at 15, 30 or 60 min post-injury, followed by one booster after 6 h. Mitochondria were isolated 24 h post-injury and assessed for respiration rates, activities of NADH dehydrogenase, cytochrome c oxidase and pyruvate dehydrogenase. SCI significantly (p < 0.05) decreased respiration rates and activities of all enzyme complexes, but ALC treatment significantly (p < 0.05) maintained mitochondrial respiration and enzyme activities compared with vehicle treatment. Critically, ALC administration in vivo at 15 min and 6 h post-injury versus vehicle, followed once daily for 7 days, significantly (p < 0.05) spared gray matter. In summary, ALC treatment maintains mitochondrial bioenergetics following contusion SCI and, thus, holds great potential as a neuroprotective therapy for acute SCI.
Patel
Samir P
SP
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, Kentucky 40536-0509, USA.
Sullivan
Patrick G
PG
Lyttle
Travis S
TS
Rabchevsky
Alexander G
AG
D000108:Acetylcarnitine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D018696:Neuroprotective Agents; D000108:Acetylcarnitine; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV