H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

Area of Science:

• Neuroscience
• Physiology
• Molecular Biology

Background:

• Hypobaric hypoxia (HH) is a known risk factor for cognitive impairment.
• The precise mechanisms underlying HH-induced neuro-physiological changes are not fully understood.

Purpose of the Study:

• To investigate the pathological brain responses to HH using a rat model.
• To elucidate the role of glio-vascular homeostasis and hydrogen sulfide (H2S) in HH-induced cognitive dysfunction.

Main Methods:

• Systems-level analysis of hippocampal transcriptome signatures.
• Statistical co-expression network analysis.
• Neuro-physiological assessments including cerebral blood flow and functional hyperemia.
• Ultra-structural, immuno-histological, and barrier function studies.
• Measurement of H2S levels in the brain.

Main Results:

• HH perturbs glio-vascular homeostasis, affecting vasomodulatory, hemostatic, and proteolytic processes.
• Chronic HH leads to a significant reduction in brain H2S levels.
• Lowered H2S levels impair hypoxic autoregulation and functional hyperemia.
• Augmenting H2S levels preserves glio-vascular homeostasis and neuro-physiological functions, including spatial memory.
• H2S augmentation reduces HH-induced neuronal apoptosis in the hippocampus.

Conclusions:

• HH-induced glio-vascular dysfunction is a key factor in cognitive impairment.
• Reduced brain H2S levels play a causal role in early HH-induced glio-vascular dysfunction and cognitive deficits.
• H2S represents a potential therapeutic target for mitigating the adverse effects of HH on the brain.