Air pollution and detrimental effects on children's brain. The need for a multidisciplinary approach to the issue complexity and challenges

Abstract

Millions of children in polluted cities are showing brain detrimental effects. Urban children exhibit brain structural and volumetric abnormalities, systemic inflammation, olfactory, auditory, vestibular and cognitive deficits v low-pollution controls. Neuroinflammation and blood-brain-barrier (BBB) breakdown target the olfactory bulb, prefrontal cortex and brainstem, but are diffusely present throughout the brain. Urban adolescent Apolipoprotein E4 carriers significantly accelerate Alzheimer pathology. Neurocognitive effects of air pollution are substantial, apparent across all populations, and potentially clinically relevant as early evidence of evolving neurodegenerative changes. The diffuse nature of the neuroinflammation and neurodegeneration forces to employ a weight of evidence approach incorporating current clinical, cognitive, neurophysiological, radiological and epidemiological research. Pediatric air pollution research requires extensive multidisciplinary collaborations to accomplish a critical goal: to protect exposed children through multidimensional interventions having both broad impact and reach. Protecting children and teens from neural effects of air pollution should be of pressing importance for public health.

Keywords: Alzheimer; Parkinson; air pollution; brain volumetric changes; cognition; cytokines; urban children; white matter hyperintensities.

Figure 1

Main mechanisms involved in brain damage associated with PM include the breakdown of nasal and olfactory pathways (A) and the alveolo-capillary pathway (B). All critical stages and effects of the biological pathways linked with (A) and (B) are shown in Figure 2. Through these pathways, PM produces systemic inflammation and travels around the body to ultimately cause pathological alterations including neuroinflammation, breakdown of the BBB, neuronal and glial damage, changes in white matter structure and volume, decline in cognitive abilities, auditory and vestibular impairment, and further deficits. (A) Nasal biopsy of 10 year-old Mexico City (MC) boy showing fine PM in the cytoplasm of epithelial cells stained with 1 μm toluidine blue. (B) Passage of PM through the alveolar capillary barrier in a Metropolitan MC young resident.

Figure 2

Biological pathways associating PM exposure with the breakdown of nasal and olfactory pathways (A) and upper/lower respiratory tract inflammation along the passage of PM through the alveolo-capillary barrier (B) are shown. Localization in the brain (see B-6) is coded by the color of the outline frames of the panels: Yellow = prefrontal cortex; Red = Olfactory bulb; Green = Brainstem; Black and Arrows = stages along the pathways. Neuroinflammation is the common denominator. In (A), nasal breakdown allows PM to directly access the brain. (A) pathway shows accumulated PM particles in the olfactory bulb. (A-1.1) Fourteen year-old MC boy with abundant particulate material in neurons in the glomerular region. (A-1.2) Accumulation of beta β amyloid, a hallmark of Alzheimer’s disease (AD). (A-2) Inflammation and degenerative changes are significant in the brainstem. For example, accumulation of α synuclein in dopaminergic pigmented neurons in an 11 year-old MC girl is a hallmark of Parkinson’s disease. In (B), the extensive respiratory tract inflammation and the passage of ultrafine PM through the alveolar capillary barrier allows PM to access the body resulting in systemic inflammation. The increased production of endothelin 1, a potent vasoconstrictor results in vasoconstriction and cerebral hypoperfusion. The BBB (see especially B-4) is damaged and triggering of autoimmune responses directly damages neural components. (B-3.1) Frontal cortex in a 15 year-old boy. Abnormal tau protein-a marker of AD- both in the neuronal body and in neurites. (B-3.2) Frontal cortex in a 17 year-old boy. A diffuse amyloid plaque –a marker of AD–(red product) is seen surrounded by glial cells. (B-4) Frontal white matter blood vessel in a 20 year-old MC male shows BBB breakdown. (B-5.1) Young 15 month-old MC dog, frontal white matter abnormal arteriole. (B-5.2) Entorhinal area perivascular inflammation in a 22 year-old female from MC. (B-6) Sagittal view of MRI of a male MC resident aged 10.