L-carnitine reduces brain injury after hypoxia-ischemia in newborn rats.
Perinatal hypoxia-ischemia remains a significant cause of neonatal mortality and neurodevelopmental disability. Numerous lines of evidence indicate that cerebral ischemic insults disrupt normal respiratory activity in mitochondria. Carnitine (3-hydroxy-4-N-trimethylammonium-butyrate) has an essential role in fatty acid transport in the mitochondrion and in modulating potentially toxic acyl-CoA levels in the mitochondrial matrix. There are no naturally occurring esterases available to reduce the accumulation of acyl-CoA but this process can be overcome by exogenous carnitine. We used a newborn rat model of perinatal hypoxia-ischemia to test the hypothesis that treatment with l-carnitine would reduce the neuropathologic injury resulting from hypoxia-ischemia in the developing brain. We found that treatment with l-carnitine during hypoxia-ischemia reduces neurologic injury in the immature rat after both a 7- and 28-d recovery period. We saw no neuroprotective effect when l-carnitine was administered after hypoxia-ischemia. Treatment with d-carnitine resulted in an increase in mortality during hypoxia-ischemia. Carnitine is easy to administer, has low toxicity, and is routinely used in neonates as well as children with epilepsy, cardiomyopathy, and inborn errors of metabolism. l-Carnitine merits further investigation as a treatment modality for the asphyxiated newborn or as prophylaxis for the at-risk fetus or newborn.
Wainwright
Mark S
MS
Division of Pediatric Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA. M-Wainwright@Northwestern.edu
Mannix
Marin K
MK
Brown
Justin
J
Stumpf
David A
DA
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002331:Carnitine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013696:Temperature
D002331:Carnitine