l-Carnitine and Acetyl-l-carnitine Roles and Neuroprotection in Developing Brain

Abstract

l-Carnitine functions to transport long chain fatty acyl-CoAs into the mitochondria for degradation by β-oxidation. Treatment with l-carnitine can ameliorate metabolic imbalances in many inborn errors of metabolism. In recent years there has been considerable interest in the therapeutic potential of l-carnitine and its acetylated derivative acetyl-l-carnitine (ALCAR) for neuroprotection in a number of disorders including hypoxia-ischemia, traumatic brain injury, Alzheimer’s disease and in conditions leading to central or peripheral nervous system injury. There is compelling evidence from preclinical studies that l-carnitine and ALCAR can improve energy status, decrease oxidative stress and prevent subsequent cell death in models of adult, neonatal and pediatric brain injury. ALCAR can provide an acetyl moiety that can be oxidized for energy, used as a precursor for acetylcholine, or incorporated into glutamate, glutamine and GABA, or into lipids for myelination and cell growth. Administration of ALCAR after brain injury in rat pups improved long-term functional outcomes, including memory. Additional studies are needed to better explore the potential of l-carnitine and ALCAR for protection of developing brain as there is an urgent need for therapies that can improve outcome after neonatal and pediatric brain injury.

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Abbreviations

ALCAR:

Acetyl-l-carnitine

OCTN2:

Organic cation transporter novel 2

CPT I:

Carnitine palmitoyltransferase I

CPT II:

Carnitine palmitoyltransferase II

CAT:

Carnitine acetyltransferase

MRS:

Magnetic resonance spectroscopy

13C-NMR:

13C-nuclear magnetic resonance spectroscopy

OGD:

Oxygen-glucose deprivation

HI:

Hypoxia-ischemia

TBI:

Traumatic brain injury

3-NPA:

3-nitropropionic acid

i.p.:

Intraperitoneal

CSF:

Cerebrospinal fluid

mTOR:

Mammalian target of rapamycin

NGF:

Nerve growth factor

pNFH:

Phosphorylated high-molecular weight neurofilament

rCMRglc:

Cerebral regional metabolic rate of glucose

TBI:

Traumatic brain injury

TCA:

Tricarboxylic acid

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Acknowledgements

The authors would like to gratefully acknowledge and thank Bruna Klippel Ferreira for her excellent effort in preparing Figs. 2 and 3, and Dr. Jaylyn Waddell and Dr. Susanna Scafidi for their very helpful suggestions. Research described from Dr. McKenna’s laboratory was supported in part by NIH Grants 5P01 HD016596 and P01 HD085928. Dr. Ferreira’s research is supported by the “Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro”, Coordination for the Improvement of Higher Education Personnel (CAPES) and National Council for Scientific and Technological Development (CNPq).

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Correspondence to Mary C. McKenna.

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Gustavo C. Ferreira and Mary C. McKenna contributed equally to this work.

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Ferreira, G.C., McKenna, M.C. l-Carnitine and Acetyl-l-carnitine Roles and Neuroprotection in Developing Brain. Neurochem Res 42, 1661–1675 (2017). https://doi.org/10.1007/s11064-017-2288-7

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Keywords

  • l-Carnitine
  • Acetyl-l-carnitine
  • Neuroprotection
  • Neonatal hypoxia-ischemia
  • Pediatric traumatic brain injury
  • Metabolism
  • Inborn errors of metabolism
  • Carnitine shuttle