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Neuroprotective Effects of Acetyl-L-Carnitine Against Oxygen-Glucose Deprivation-Induced Neural Stem Cell Death

Abstract

Deprivation of oxygen and glucose is the main cause of neuronal cell death during cerebral infarction and can result in severe morbidity and mortality. In general, the neuroprotective therapies that are applied after ischemic stroke have been unsuccessful, despite many investigations. Acetyl-L-carnitine (ALCAR) plays an important role in mitochondrial metabolism and in modulating the coenzyme A (CoA)/acyl-CoA ratio. We investigated the protective effects of ALCAR against oxygen-glucose deprivation (OGD) in neural stem cells (NSCs). We measured cell viability, proliferation, apoptosis, and intracellular signaling protein levels after treatment with varying concentrations of ALCAR under OGD for 8 h. ALCAR protected NSCs against OGD by reducing apoptosis and restoring proliferation. Its protective effects are associated with increases in the expression of survival-related proteins, such as phosphorylated Akt (pAkt), phosphorylated glycogen synthase kinase 3b (pGSK3b), B cell lymphoma 2 (Bcl-2), and Ki-67 in NSCs that were injured by OGD. ALCAR also reduced the expression of death-related proteins, such as Bax, cytosolic cytochrome C, cleaved caspase-9, and cleaved caspase-3. We concluded that ALCAR exhibits neuroprotective effects against OGD-induced damage to NSCs by enhancing the expression of survival signals and decreasing that of death signals.

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Acknowledgments

This work was supported by a grant from the Korea Research Foundation (2015R1A2A2A04004865) and a grant from the NanoBio R&D Program of the Korea Science and Engineering Foundation, funded by the Ministry of Education, Science and Technology (2007-04717).

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Correspondence to Seong-Ho Koh.

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Seong Wan Bak and Hojin Choi contributed equally to this work.

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Bak, S.W., Choi, H., Park, HH. et al. Neuroprotective Effects of Acetyl-L-Carnitine Against Oxygen-Glucose Deprivation-Induced Neural Stem Cell Death. Mol Neurobiol 53, 6644–6652 (2016). https://doi.org/10.1007/s12035-015-9563-x

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  • DOI: https://doi.org/10.1007/s12035-015-9563-x

Keywords

  • Stroke
  • Oxygen glucose deprivation
  • Acetyl-L-carnitine
  • Phosphatidylinositol 3-kinase