ß-Hydroxybutyrate Improves Mitochondrial Function After Transient Ischemia in the Mouse

Area of Science:

• Neuroscience
• Metabolic research
• Mitochondrial biology

Background:

• Ketone bodies, like beta-hydroxybutyrate (BHB), and ketogenic diets show potential neuroprotective effects in neurodegenerative diseases.
• Ischemic stroke remains a leading cause of death and disability, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the neuroprotective effects of a single beta-hydroxybutyrate (BHB) administration following transient focal cerebral ischemia in a mouse model.
• To assess the impact of BHB on mitochondrial function and neurological recovery after ischemic stroke.

Main Methods:

• Transient focal cerebral ischemia was induced in mice by middle cerebral artery occlusion for 90 minutes.
• Beta-hydroxybutyrate (BHB) was administered intraperitoneally (30 mg/kg) immediately after reperfusion.
• Neurological scores were evaluated 24 hours post-ischemia. Mitochondrial oxygen consumption and activity of respiratory complexes (I, II, IV) were measured in brain tissue.

Main Results:

• BHB administration significantly improved neurological scores 24 hours after ischemia.
• Mitochondrial oxygen consumption, particularly for complexes I and II, was enhanced by BHB treatment at 24 hours post-ischemia.
• Elevated plasma and brain BHB levels were observed 24 hours post-administration, without altering key mitochondrial intermediates.

Conclusions:

• A single dose of BHB demonstrates acute neuroprotective effects and improves mitochondrial respiration following ischemic stroke in mice.
• The beneficial effects of BHB on mitochondrial function appear transient, lasting approximately 1-2 days.
• Endogenous BHB production may play a complementary role to exogenous administration in stroke recovery.