Korean J Pediatr.  2012 Jul;55(7):238-248. 10.3345/kjp.2012.55.7.238.

Neuroprotective effects of L-carnitine against oxygen-glucose deprivation in rat primary cortical neurons

Affiliations
  • 1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. yschang@skku.edu
  • 2Samsung Biochemical Research Institute, Seoul, Korea.

Abstract

PURPOSE
Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD).
METHODS
Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO) and propidium iodide (PI) were counted, and lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels were measured. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 microM, 10 microM, and 100 microM) on OGD-induced neurotoxicity.
RESULTS
Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 microM and 100 microM of L-carnitine compared with the untreated OGD group (P<0.05). The application of L-carnitine at 100 microM significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P<0.05).
CONCLUSION
L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

Keyword

L-carnitine; Neuroprotective effect; Oxygen-glucose deprivation; Neurons; Hypoxia-Ischemia

MeSH Terms

Acridine Orange
Acyl Coenzyme A
Animals
Apoptosis
Brain Injuries
Carnitine
Deoxyuracil Nucleotides
Deoxyuridine
Embryonic Structures
Humans
Hypoxia-Ischemia, Brain
Infant
Infant Mortality
L-Lactate Dehydrogenase
Necrosis
Neurons
Neuroprotective Agents
Propidium
Rats
Reactive Oxygen Species
Tetrazolium Salts
Thiazoles
Uridine
Acridine Orange
Acyl Coenzyme A
Carnitine
Deoxyuracil Nucleotides
Deoxyuridine
L-Lactate Dehydrogenase
Neuroprotective Agents
Propidium
Reactive Oxygen Species
Tetrazolium Salts
Thiazoles
Uridine
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