
Contents
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The Blood–Brain Barrier The Blood–Brain Barrier
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Cellular Associations at the BBB Cellular Associations at the BBB
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ECs ECs
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Astrocytes Astrocytes
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Pericytes Pericytes
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Molecules at the BBB Molecules at the BBB
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Tight Junctions Tight Junctions
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Leukocyte Adhesion Molecules Leukocyte Adhesion Molecules
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Transporters Transporters
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Other Components Other Components
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Functions of the BBB Functions of the BBB
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Regulation of Ion Concentration Regulation of Ion Concentration
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Entry of Macromolecules Entry of Macromolecules
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Regulation of Neurotransmitters Regulation of Neurotransmitters
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Elimination of Neurotoxins Elimination of Neurotoxins
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Transport of Nutrients to the Brain Transport of Nutrients to the Brain
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Ketogenic Diet Ketogenic Diet
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Regulation of Cerebral Ketone Uptake Regulation of Cerebral Ketone Uptake
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Anti-inflammatory Effects of KBs Anti-inflammatory Effects of KBs
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Neuroprotective Effects of KBs Neuroprotective Effects of KBs
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Effects of KBs on the BBB Effects of KBs on the BBB
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Concluding Remarks Concluding Remarks
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References References
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29 Effects of the Ketogenic Diet on the Blood–Brain Barrier
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Published:March 2022
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Abstract
The ketogenic diet (KD) is considered a valuable nonpharmacologic approach for treating multiple neurologic disorders, for attenuating the neurologic sequelae of brain injury, and for reducing seizure burden. The mechanisms by which the KD works are largely unknown. Glucose is virtually the sole energy source for the brain. However, during times of starvation, the liver produces ketone bodies (KBs), which can supply up to 70% of the brain’s energy needs. Acetoacetate and β-hydroxybutyrate (βHB) are the most abundant KBs, whereas acetone, present in small quantities, is not commonly utilized as an energy source. Ketones are also advantageous in neuroinflammatory conditions because they decrease the production of free radicals. Studies suggest a significant increase in cerebral ketone uptake after brain injury. KBs are always present in the blood, and their levels increase after high-fat dietary intake, prolonged exercise, or extended fasting. Thus, one can predict an effect on the brain capillary endothelium from high levels of ketones in the blood. Prolonged exposure of blood–brain barrier (BBB) endothelial cells to KBs induces expression of monocarboxylate transporters and enhances the cerebral uptake rate of KBs. In addition, cell migration and expression of gap junction proteins are upregulated by KBs. Altogether, reports suggest that the beneficial effects of the KD may depend on increased brain uptake of KBs to match metabolic demand as well as repair of the disrupted BBB. As the effects of KBs on the BBB and transport mechanisms across the BBB are better understood, it will be possible to develop alternative strategies to optimize therapeutic benefits for brain disorders where the BBB is compromised.
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