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Ischemic preconditioning with a ketogenic diet improves brain ischemic tolerance through increased extracellular adenosine levels and hypoxia-inducible factors.
- Source :
-
Brain research [Brain Res] 2017 Jul 15; Vol. 1667, pp. 11-18. Date of Electronic Publication: 2017 Apr 18. - Publication Year :
- 2017
-
Abstract
- Ischemic tolerance reduces brain damage and neurological dysfunction after brain ischemia. A ketogenic diet (KD) has disease-modifying effects in several neurodegenerative disorders. In this study, we fed mice with a KD for three weeks and performed reversible middle cerebral artery occlusion (MCAO) in the animals. KD-fed mice had a significantly reduced infarct volume, increased regional cerebral blood flow (rCBF) and extracellular adenosine levels in both the ischemic and the reperfusion phases. In vitro and in vivo experiments revealed that the KD-induced neuroprotection was mediated through the adenosine A1 receptor. The KD increased Akt and ERK1/2 phosphorylation via A1R activation. Besides, the KD also upregulated robustly HIF-1α/HIF-2α and HIF regulated genes, such as VEGF and EPO. A three-week preconditioning period with a KD improved ischemic tolerance in mice with MCAO. The underlying mechanisms might include elevated extracellular adenosine levels, and increased Akt and ERK1/2 phosphorylation via A1 adenosine receptor activation, together with upregulated HIFs and HIF-regulated genes.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors metabolism
Brain blood supply
Brain pathology
Brain Ischemia pathology
Cell Line, Tumor
Cerebrovascular Circulation physiology
Disease Models, Animal
Extracellular Space metabolism
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
MAP Kinase Signaling System physiology
Male
Mice, Inbred BALB C
Neuroprotection physiology
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
Random Allocation
Receptor, Adenosine A1 metabolism
Vascular Endothelial Growth Factor A metabolism
Adenosine metabolism
Brain metabolism
Brain Ischemia metabolism
Brain Ischemia therapy
Diet, Ketogenic
Ischemic Preconditioning
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1667
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 28427869
- Full Text :
- https://doi.org/10.1016/j.brainres.2017.04.010