title: White matter hyperintensities, systemic inflammation, brain growth, and cognitive functions in children exposed to air pollution.
abstract: Air pollution exposures are linked to neuroinflammation and neuropathology in young urbanites. Forty percent of exposed children and young adults exhibit frontal tau hyperphosphorylation and 51% have amyloid-β diffuse plaques compared to 0% in low pollution controls. In older adults, white matter hyperintensities (WMH) are associated with cognitive deficits while inflammatory markers correlate with greater atrophy than expected for age. We investigated patterns of WMH, magnetic resonance imaging (MRI) volume growth, blood inflammatory mediators, and cognition in matched children from two urban cohorts: one severely and one minimally exposed to air pollution. Baseline and one year follow-up measurements of cognitive abilities, brain MRI volumes, and blood were collected in 20 Mexico City (MC) children (10 with WMH+, and 10 without WMH-) and 10 matched controls (WMH-). MC WMH- children display the profile of classical pro-inflammatory defensive responses: high interleukin 12, production of powerful pro-inflammatory cytokines, and low concentrations of key cytokines and chemokines associated with neuroprotection. MC WMH+ children exhibit a response involved in resolution of inflammation, immunoregulation, and tissue remodeling. The MC WMH+ group responded to the air pollution-associated brain volumetric alterations with white and grey matter volume increases in temporal, parietal, and frontal regions and better cognitive performance compared to MC WMH-. We conclude that complex modulation of cytokines and chemokines influences children's central nervous system structural and volumetric responses and cognitive correlates resulting from environmental pollution exposures. Identification of biomarkers associating systemic inflammation to brain growth is critical for detecting children at higher risk for cognitive deficits and neurodegeneration, thereby warranting early implementation of neuroprotective measures.
authors.affiliation: Instituto Nacional de Pediatría, Mexico City, Mexico. lilian.calderon-garciduenas@umontana.edu
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.forename: Antonieta
authors.initials: A
authors.lastname: Mora-Tiscareño
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.forename: Gilberto
authors.initials: G
authors.lastname: Gómez-Garza
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.forename: Esperanza
authors.initials: E
authors.lastname: Carlos
authors.forename: Edelmira
authors.initials: E
authors.lastname: Solorio-López
authors.forename: Humberto
authors.initials: H
authors.lastname: Medina-Cortina
authors.forename: Michael
authors.initials: M
authors.lastname: Kavanaugh
authors.forename: Amedeo
authors.initials: A
authors.lastname: D'Angiulli
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D002648:Child; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D002658:Developmental Disabilities / Q000139:chemically induced*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D021621:Imaging, Three-Dimensional; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007958:Leukocyte Count; D056784:Leukoencephalopathies / Q000139:chemically induced* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests
chemical_list: D016207:Cytokines