Aerospace stressors and brain health in military aviators: a glymphatic-neurovascular framework.

Abstract

Military aviation exposes aircrew to interacting physiological and operational stressors that are often studied in isolation. These stressors are experienced by the whole body: pulmonary, cardiovascular, musculoskeletal, endocrine, and immune responses may influence cerebral perfusion, blood-brain barrier function, fatigue, and recovery. Evidence from aviation cohorts, altitude-chamber studies, and adjacent fields suggests that some exposures may converge on neurovascular, blood-brain barrier, perivascular, and inflammatory pathways before overt neurological disease is apparent. This narrative review evaluates the glymphatic system as one potentially important component of that broader injury-and-recovery network, rather than as a sole or established primary mechanism. We synthesize evidence concerning hypobaria and decompression, intermittent hypoxia and hyperoxia, high +Gz, sleep and circadian disruption, operational wakefulness-promoting agents, noise, cosmic ionizing radiation, and context-dependent chemical exposures. Direct human evidence of glymphatic dysfunction in tactical aviators remains absent, and findings from lower-intensity hypobaric exposure and retrospective clinical cohorts are mixed or null. Exposure profiles also differ substantially among fighter, cargo/tanker, helicopter, and remotely piloted aircraft communities. We therefore propose an exposure-resolved research agenda combining longitudinal neuroimaging, circulating biomarkers, electroencephalography, cognitive testing, sleep phenotyping, dosimetry, and controlled single- and combined-stressor experiments. This calibrated glymphatic-neurovascular framework generates testable hypotheses about cumulative brain stress and recovery while preserving alternative explanations involving direct tissue injury, cerebral perfusion, endothelial dysfunction, oxidative stress, systemic and central inflammation, and autonomic regulation.