L-Carnitine Reduces Brain Injury after Hypoxia-Ischemia in Newborn Rats

Mark S. Wainwright*, Marin K. Mannix, Justin Brown, David A. Stumpf

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)688-695
Number of pages8
JournalPediatric research
Volume54
Issue number5
DOIs
StatePublished - Nov 2003

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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