The impact of military occupational combustion smoke inhalation on neuroinflammation and brain health.

Airborne combustion emissions from military burn pits, wildfires, and urban/industrial sources are increasingly recognized as a component of the neurotoxic exposome, with potential consequences extending beyond cardiopulmonary disease to brain health. These aerosols comprise heterogeneous mixtures of fine and ultrafine particulate matter (PM₂.₅/PM₀.₁), polycyclic aromatic hydrocarbons, volatile organic compounds, metals, and reactive gases whose composition varies with fuel type, combustion efficiency, and atmospheric aging. Evidence from experimental models, epidemiology, and exposed human cohorts supports two principal routes by which inhaled pollutants may influence the central nervous system: (i) the lung-brain axis, where pulmonary oxidative injury and systemic immune activation promote endothelial dysfunction and compromise blood-brain barrier integrity; and (ii) the olfactory (nose-to-brain) pathway, in which ultrafine and lipophilic constituents interact with the olfactory neuroepithelium and are associated with early neuroimmune changes in olfactory-connected brain regions. At the cellular level, these exposures converge on microglial and astrocytic activation, TLR-NF-κB and inflammasome signaling, mitochondrial dysfunction, and lipid peroxidation, processes that can sustain chronic neuroinflammation and plausibly interact with 'second hits' such as traumatic brain injury, psychological stress, heat stress, sleep disruption, and cardiometabolic comorbidity. Veterans and wildland firefighters represent sentinel occupational groups for defining exposure-biomarker-outcome relationships. This review brings together current evidence linking combustion-derived aerosols to neuroinflammatory and neurodegeneration-relevant mechanisms, highlighting source-specific considerations for military operational exposure, and outlines translational strategies for exposure monitoring, multi-omic biomarker discovery (blood and nasal/olfactory sampling), and early risk stratification to enable targeted prevention in vulnerable populations.