HBOT: From Mechanisms to Cognitive Enhancement (Review)

Key Message

This review shows: Intermittent HBOT modulates central cellular pathways (including SIRT1, Nrf2, HIF-1α), improves cerebral blood flow, metabolism, and microstructure, and is linked to cognitive gains in studies on stroke, TBI, MCI/AD, as well as in healthy individuals. (PMC)

Background – Why HBOT for the Brain?

HBOT increases dissolved oxygen beyond 1 ATA, thereby reaching underperfused areas. Beyond its established indications (e.g., CO intoxication, radiation injury), HBOT is increasingly investigated for neurocognitive applications. Mechanistically, HBOT influences oxidative stress, inflammation, mitochondrial function, apoptosis, angiogenesis, and neurogenesis. (PMC)

What Does the Evidence in the Review Say?

After Brain Injury (Stroke, TBI)

• Chronic post-stroke phase: 40–60 sessions (~2 ATA) → significant improvements in memory and executive functions; parallel increases in CBF and metabolism. Effects lasted months in studies.

• TBI (mild/chronic): Evidence of neuroplasticity, improved CBF, and better white/gray matter microstructure; functional gains in cognition and daily living.

Neurodegeneration (MCI/AD, Vascular Dementia)

• MCI/AD: Improved cognitive scores and brain metabolism (PET/FDG, region-specific). Some effects persisted 1–3 months post-HBOT.

• Vascular dementia: Cognitive gains (e.g., MMSE ↑); Humanin (a mitochondrial protective peptide) ↑ → supports mitochondrial mechanisms.

Healthy Individuals & Healthy Aging

• Young & older adults: Improved working/episodic memory, learning curve, and interference resistance. In older adults, effects were coupled with CBF gains.

• Short-term HBOT (e.g., 15 days): Often insufficient; 40–60 sessions yielded more sustainable benefits.

Key Mechanisms (Simplified)

• SIRT1/Nrf2: Antioxidant response & mitochondrial biogenesis → ROS balance and cell protection.

• HIF-1α: Intermittent hyperoxia triggers a hypoxia-like adaptation → angiogenesis, metabolic shifts.

• Wnt/neurogenesis, anti-apoptosis, inflammation modulation: Underpin structural and functional improvements (see full-text figures in review).

Protocol Notes (from Reviewed Studies)

• Common: 40–60 sessions, 5×/week, 2–3 ATA, ~90 min with air breaks.

• Dose–time pattern matters: intermittent & longer-term → adaptive (hormetic) rather than purely oxidative.

Limitations

• Narrative review (no original cohort).

• Heterogeneous protocols and populations → findings not directly transferable.

• More RCTs with sham control, long-term follow-up, and standardized endpoints are needed.

For Practice (Website Takeaways)

• HBOT offers biologically plausible pathways to cognitive enhancement (via CBF, metabolism, microstructure).

• Early intervention (e.g., in MCI/vascular dementia) appears more promising than late AD stages.

• Personalization via biomarkers (CBF, cognitive domains) and protocol fine-tuning recommended. (PMC)