129 From air to brain: investigating the pulmonary-neural axis

Abstract Air pollution is increasingly recognised as a potent contributor to the development and exacerbation of diverse neurological and psychiatric conditions. This keynote address explores the fundamental mechanisms through which inhaled particulate pollutants disrupt central nervous system homeostasis. It specifically focuses on the lung to brain axis while highlighting the critical yet often ignored distinction between size dependent physical effects and the chemical impact of soluble particulate matter components. A central theme of this investigation is the interplay between particle size and solubility. While insoluble ultrafine particles may translocate as intact entities via the olfactory and trigeminal nerves the soluble fractions of particulate matter release neurotoxic metals and organic compounds into the systemic circulation. Crucially the inflammatory and oxidative potential of particles varies significantly by source. By evaluating the specific pulmonary response to these diverse sources, we gain vital insight into the downstream systemic and neurological impacts. Inhaled pollutants trigger the production of inflammatory mediators within the pulmonary parenchyma. These cytokines and oxidative stress markers alongside translocated constituents enter the systemic circulation from the pulmonary capillaries. Once systemic these neurotoxicants gain access to the brain by compromising the integrity of the blood-brain barrier. Such systemic infiltration triggers a cascade of microglial activation and oxidative stress. These mechanisms significantly impair neurodevelopment in younger cohorts by disrupting synaptic pruning and myelination. Furthermore, this chronic neuroinflammation is a key driver of cognitive decline and accelerated brain ageing in later life. These interconnected pathways highlight the profound vulnerability of the human brain to environmental toxins and underscore the urgent need to prioritise air quality to protect cognitive health across the entire life course.