Microglial-Neurovascular Interactions and Neuronal Function at High Altitude
Abstract
Millions of people worldwide live at high altitude without evolutionary adaptation, and millions more travel to and stay at high altitudes for work or recreational activities that result in chronic exposure to this austere environment. Chronic high altitude exposure is characterized by hypobaric hypoxia, where a low pressure low oxygen environment reduces the availability of oxygen for respiration and distribution throughout the body. Compromised tissue oxygenation has long lasting effects even after return to normoxic conditions, causing a range of physiological disturbances including cognitive dysfunction. During the acute stages of exposure, the body and the central and peripheral nervous systems undergo short term acclimatization processes relying on increased heart rate, respiration and vasodilation to improve oxygen delivery. Prolonged stays at high altitude are associated with enhanced brain angiogenesis, blood-brain barrier disruption, and altered metabolic profiles in the brain and periphery, as well as presence of inflammatory markers leading to memory deficits and cognitive decline. Previous preclinical research in the laboratory identified increased phagocytic activity of microglia in mice after chronic 12 week simulated high altitude exposure, as well as an increase in brain vasculature and evidence of blood-brain barrier leakage. There was also an effect of high altitude on brain glucose metabolism, altered hippocampal transcriptional profiles, and behavioral deficits relating to hippocampal mediated learning and memory. Functional impairments following shorter (3 week) high altitude exposure are hypothesized to be influenced by region-specific neurovascular and inflammatory interactions, and the studies presented here explore those connections.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 29, 2022
- Accession Number
- AD1186385
Entities
People
- Kathleen Anne Guzek Whiting
Organizations
- Uniformed Services University of the Health Sciences