Lehto 2022 Neurochem Res

Lehto A, Koch K, Barnstorf-Brandes J, Viel C, Fuchs M, Klein J (2022) ß-Hydroxybutyrate improves mitochondrial function after transient ischemia in the mouse. https://doi.org/10.1007/s11064-022-03637-6

» Neurochem Res 47:3241-49. PMID: 35674929 Open Access

Lehto Allna, Koch Konrad, Barnstorf-Brandes Johanna, Viel Christian, Fuchs Marius, Klein Jochen (2022) Neurochem Res

Abstract: ß-Hydroxybutyrate (BHB) is a ketone body formed in high amounts during lipolysis and fasting. Ketone bodies and the ketogenic diet were suggested as neuroprotective agents in neurodegenerative disease. In the present work, we induced transient ischemia in mouse brain by unilaterally occluding the middle cerebral artery for 90 min. BHB (30 mg/kg), given immediately after reperfusion, significantly improved the neurological score determined after 24 h. In isolated mitochondria from mouse brain, oxygen consumption by the complexes I, II and IV was reduced immediately after ischemia but recovered slowly over 1 week. The single acute BHB administration after reperfusion improved complex I and II activity after 24 h while no significant effects were seen at later time points. After 24 h, plasma and brain BHB concentrations were strongly increased while mitochondrial intermediates (citrate, succinate) were unchanged in brain tissue. Our data suggest that a single administration of BHB may improve mitochondrial respiration for 1-2 days but not for later time points. Endogenous BHB formation seems to complement the effects of exogenous BHB administration. • Keywords: Complex I, Complex II, Glucose, Microdialysis, Oxidative phosphorylation, Stroke • Bioblast editor: Plangger M

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Neurodegenerative  Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2023-05