Neuroprotective effects of pre-treatment with l-carnitine and acetyl-L-carnitine on ischemic injury in vivo and in vitro

Int J Mol Sci. 2012;13(2):2078-2090. doi: 10.3390/ijms13022078. Epub 2012 Feb 15.

Abstract

The therapeutic effect of stroke is hampered by the lack of neuroprotective drugs against ischemic insults beyond the acute phase. Carnitine plays important roles in mitochondrial metabolism and in modulating the ratio of coenzyme A (CoA)/acyl-CoA. Here, we investigate the neuroprotective effects of l-carnitine (LC) and Acetyl-l-carnitine (ALC) pre-treatment on ischemic insults under the same experimental conditions. We used a transient middle cerebral artery occlusion (MCAO) model to evaluate the protective roles of LC and ALC in acute focal cerebral ischemia in vivo and to understand the possible mechanisms using model of PC12 cell cultures in vitro. Results showed that ALC, but not LC, decreased infarction size in SD rats after MCAO in vivo. However, both LC and ALC pretreatment reduced oxygen-glucose deprivation (OGD)-induced cell injury and decreased OGD-induced cell apoptosis and death in vitro; at the same time, both of them increased the activities of super oxide dismutase (SOD) and ATPase, and decreased the concentration of malondialdehyde (MDA) in vitro. Thus, our findings suggested that LC and ALC pre-treatment are highly effective in the prevention of neuronal cell against ischemic injury in vitro, however, only ALC has the protective effect on neuronal cell injury after ischemia in vivo.

Keywords: Acetyl-l-carnitine; ischemia; l-carnitine; neuroprotection; oxygen-glucose deprivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Brain Ischemia / etiology
  • Brain Ischemia / prevention & control*
  • Carnitine / pharmacology*
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Malondialdehyde / metabolism
  • Neuroprotective Agents / pharmacology*
  • Oxygen / pharmacology
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism

Substances

  • Neuroprotective Agents
  • Malondialdehyde
  • Acetylcarnitine
  • Superoxide Dismutase
  • Carnitine
  • Oxygen