Air Pollution and Brain Damage

Exposure to complex mixtures of air pollutants produces infl ammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemica l expression of nuclear factor-kappa beta (NF-κB) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF-κB and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequent damage included alterations of the blood—brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques , and neurofi brillary tangles. Persistent pulmonary infl ammation and deteriorating olfactory and respiratory barriers may play a role in the neuropathology observed in the brains of these highly exposed canines. Neurodegenerative disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

[1]  H. Pfister,et al.  Differential expression of nitric oxide synthases in bacterial meningitis: role of the inducible isoform for blood-brain barrier breakdown. , 2001, The Journal of infectious diseases.

[2]  R. Devlin,et al.  Canines as sentinel species for assessing chronic exposures to air pollutants: part 2. Cardiac pathology. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[3]  K. Audus,et al.  Nitric oxide and blood-brain barrier integrity. , 2001, Antioxidants & redox signaling.

[4]  Jau-Shyong Hong,et al.  Molecular consequences of activated microglia in the brain: overactivation induces apoptosis , 2001, Journal of neurochemistry.

[5]  Bin Liu,et al.  Molecular consequences of activated microglia in the brain: overactivation induces apoptosis. , 2001 .

[6]  P A Scheff,et al.  Volatile organic compounds, polycyclic aromatic hydrocarbons and elements in the air of ten urban homes. , 2001, Indoor air.

[7]  Nigel J. Cairns,et al.  Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages , 2001, Neuroreport.

[8]  Mark P. Mattson,et al.  NF-κB in neuronal plasticity and neurodegenerative disorders , 2001 .

[9]  R. Gamelli,et al.  Myeloid Commitment Shifts Toward Monocytopoiesis After Thermal Injury and Sepsis , 2001, Annals of surgery.

[10]  J. Poirier,et al.  Apolipoprotein E and Alzheimer's Disease A Role in Amyloid Catabolism , 2000, Annals of the New York Academy of Sciences.

[11]  P. Catalano,et al.  Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines. , 2000, Environmental health perspectives.

[12]  P J Lioy,et al.  Ozone and limonene in indoor air: a source of submicron particle exposure. , 2000, Environmental health perspectives.

[13]  J. Creason,et al.  The 1998 Baltimore Particulate Matter Epidemiology–Exposure Study: Part 1. Comparison of ambient, residential outdoor, indoor and apartment particulate matter monitoring , 2000, Journal of Exposure Analysis and Environmental Epidemiology.

[14]  P. Jaques,et al.  Respiratory dose of inhaled ultrafine particles in healthy adults , 2000, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[15]  R. Sherwin,et al.  Centriacinar region inflammatory disease in young individuals: a comparative study of Miami and Los Angeles residents , 2000, Virchows Archiv.

[16]  H. Sies,et al.  Selective upregulation of inducible nitric oxide synthase (iNOS) by lipopolysaccharide (LPS) and cytokines in microglia: In vitro and in vivo studies , 2000, Glia.

[17]  T. Johnson,et al.  Prediction of hourly microenvironmental concentrations of fine particles based on measurements obtained from the Baltimore scripted activity study , 2000, Journal of Exposure Analysis and Environmental Epidemiology.

[18]  R. Devlin,et al.  Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. , 2000, American journal of respiratory and critical care medicine.

[19]  R. Mohney,et al.  Regional Difference in Susceptibility to Lipopolysaccharide-Induced Neurotoxicity in the Rat Brain: Role of Microglia , 2000, The Journal of Neuroscience.

[20]  Kathryn Ross,et al.  Prevalence of Alzheimer’s Disease and Other Dementing Disorders in an Urban Community of Beijing, China , 2000, Neuroepidemiology.

[21]  H. Tjälve,et al.  Intranasal instillation of aflatoxin B(1) in rats: bioactivation in the nasal mucosa and neuronal transport to the olfactory bulb. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[22]  J. Henriksson,et al.  Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[23]  C. J. Chung,et al.  EXPOSURE TO AIR POLLUTION IS ASSOCIATED WITH LUNG HYPERINFLATION IN HEALTHY CHILDREN AND ADOLESCENTS IN SOUTHWEST MEXICO CITY: A Pilot Study , 2000, Inhalation toxicology.

[24]  Edward W. Johnson,et al.  Immunocytochemical characteristics of cells and fibers in the nasal mucosa of young and adult macaques , 2000, The Anatomical record.

[25]  J. Clemens,et al.  Cerebral ischemia: gene activation, neuronal injury, and the protective role of antioxidants. , 2000, Free radical biology & medicine.

[26]  C. Plata-salamán,et al.  Inflammation and Alzheimer’s disease , 2000, Neurobiology of Aging.

[27]  L. Mucke,et al.  Transforming growth factor (TGF)-β1 modifies Alzheimer's-type pathology in a transgenic mice and humans , 2000, Neurobiology of Aging.

[28]  M. Takiguchi,et al.  Induction of Endothelial Nitric-oxide Synthase in Rat Brain Astrocytes by Systemic Lipopolysaccharide Treatment* , 2000, The Journal of Biological Chemistry.

[29]  Rodney W. Johnson,et al.  Interleukin (IL)-10 inhibits IL-6 production in microglia by preventing activation of NF-kappaB. , 2000, Brain research. Molecular brain research.

[30]  P. Grammas A damaged microcirculation contributes to neuronal cell death in Alzheimer’s disease☆ , 2000, Neurobiology of Aging.

[31]  G Kobal,et al.  Anterior Distribution of Human Olfactory Epithelium , 2000, The Laryngoscope.

[32]  L. Acarín,et al.  STAT3 and NFκB Activation Precedes Glial Reactivity in the Excitotoxically Injured Young Cortex but not in the Corresponding Distal Thalamic Nuclei , 2000, Journal of neuropathology and experimental neurology.

[33]  S. Rivest,et al.  How the Blood Talks to the Brain Parenchyma and the Paraventricular Nucleus of the Hypothalamus During Systemic Inflammatory and Infectious Stimuli (44459) , 2000, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[34]  W. Streit,et al.  Microglial Response to Brain Injury: A Brief Synopsis , 2000, Toxicologic pathology.

[35]  P. Lantos,et al.  β‐Amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer’s disease , 1999 .

[36]  J. Llibre,et al.  [Dementia syndrome and risk factors in adults older than 60 years old residing in Habana]. , 1999, Revista de neurologia.

[37]  R. Garman,et al.  Histopathology of Nasal Olfactory Mucosa from Selected Inhalation Toxicity Studies Conducted with Volatile Chemicals , 1999, Toxicologic pathology.

[38]  J. Sulon,et al.  Inflammatory effect of intratracheal instillation of ultrafine particles in the rabbit: role of C-fiber and mast cells. , 1999, Toxicology and applied pharmacology.

[39]  Laura Fratiglioni,et al.  Worldwide Prevalence and Incidence of Dementia , 1999, Drugs & aging.

[40]  H. Link,et al.  Is there a balance between microglia and astrocytes in regulating Th1/Th2-cell responses and neuropathologies? , 1999, Immunology today.

[41]  J C Chow,et al.  Particulate Air Pollution in Mexico City: A Collaborative Research Project. , 1999, Journal of the Air & Waste Management Association.

[42]  D. Giulian Microglia and the immune pathology of Alzheimer disease. , 1999, American Journal of Human Genetics.

[43]  J. Rhodin,et al.  Animal model of vascular inflammation. , 1999, Journal of submicroscopic cytology and pathology.

[44]  T J Bucci,et al.  The Nomenclature of Cell Death: Recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists , 1999, Toxicologic pathology.

[45]  K. Divine,et al.  Quantitative particle-induced X-ray emission imaging of rat olfactory epithelium applied to the permeability of rat epithelium to inhaled aluminum. , 1999, Chemical research in toxicology.

[46]  I. Adamson,et al.  Cell injury and interstitial inflammation in rat lung after inhalation of ozone and urban particulates. , 1999, American journal of respiratory cell and molecular biology.

[47]  I. Ferrer,et al.  Age-related Changes in the Brain of the Dog , 1999, Veterinary pathology.

[48]  J. Kelley,et al.  Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[49]  John Ngai,et al.  Development of the vertebrate main olfactory system , 1999, Current Opinion in Neurobiology.

[50]  L. Calderón-Garcidueñas,et al.  Nasal epithelium as a sentinel for airborne environmental pollution. , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[51]  R. H. MacTurk,et al.  Age‐Related Changes in the Prevalence of Smell/Taste Problems among the United States Adult Population: Results of the 1994 Disability Supplement to the National Health Interview Survey (NHIS) , 1998, Annals of the New York Academy of Sciences.

[52]  S. Zhong,et al.  Meteorological factors associated with inhomogeneous ozone concentrations within the Mexico City basin , 1998 .

[53]  D. Wartenberg,et al.  Environmental causes for sinonasal cancers in pet dogs, and their usefulness as sentinels of indoor cancer risk. , 1998, Journal of toxicology and environmental health. Part A.

[54]  C. Hock,et al.  Histological Markers in Nasal Mucosa of Patients with Alzheimer’s Disease , 1998, European Neurology.

[55]  Ren-Shen Lee,et al.  Oxidized LDL promotes vascular endothelial cell pinocytosis via a prooxidation mechanism , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[56]  Jau-Shyong Hong,et al.  Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures , 1998, Journal of Neuroimmunology.

[57]  I Maruyama,et al.  Biology of endothelium , 1998, Lupus.

[58]  S. Takemori,et al.  A rare case of acoustic neuroma extending from the cerebellopontine angle to the external auditory canal , 1998, Journal of Clinical Neuroscience.

[59]  Brian J Cummings,et al.  The progression of β-amyloid deposition in the frontal cortex of the aged canine , 1997, Brain Research.

[60]  J. Carter,et al.  Cytokines and particle-induced inflammatory cell recruitment. , 1997, Environmental health perspectives.

[61]  J. Finkelstein,et al.  Particulate-cell interactions and pulmonary cytokine expression. , 1997, Environmental health perspectives.

[62]  P. Weigel,et al.  Production of Neurotoxic Factors by Brain Endothelium in Alzheimer's Disease a , 1997, Annals of the New York Academy of Sciences.

[63]  D. Lynam,et al.  Personal exposure to elements in Mexico City air. , 1997, The Science of the total environment.

[64]  S. Okuyama The first attempt at radioisotopic evaluation of the integrity of the nose-brain barrier. , 1997, Life sciences.

[65]  É. Mezey,et al.  Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Gregory G. Brown,et al.  Occupational exposures to metals as risk factors for Parkinson's disease , 1997, Neurology.

[67]  O. Brändli [Are inhaled dust particles harmful for our lungs?]. , 1996, Schweizerische medizinische Wochenschrift.

[68]  P. S. Gilmour,et al.  Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro. , 1996, Thorax.

[69]  T. Umemura,et al.  Age‐related changes in the olfactory system of dogs , 1996, Neuropathology and applied neurobiology.

[70]  J. Miranda,et al.  A receptor model for atmospheric aerosols from a southwestern site in Mexico City , 1996 .

[71]  J. Wegiel,et al.  Subpopulation of dogs with severe brain parenchymal β amyloidosis distinguished with cluster analysis , 1996, Brain Research.

[72]  T. Corona,et al.  Multiple sclerosis in Mexico: hospital cases at the National Institute of Neurology and Neurosurgery, Mexico City. , 1996, Neurologia.

[73]  Brian J Cummings,et al.  The canine as an animal model of human aging and dementia , 1996, Neurobiology of Aging.

[74]  J. Geddes,et al.  Age-specific onset of β-amyloid in Beagle brains , 1996, Neurobiology of Aging.

[75]  Luz Claudio,et al.  Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients , 1995, Acta Neuropathologica.

[76]  D. Blake,et al.  Urban Leakage of Liquefied Petroleum Gas and Its Impact on Mexico City Air Quality , 1995, Science.

[77]  A D Roses,et al.  Apolipoprotein E and Alzheimer disease. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[78]  Diederick E Grobbee,et al.  Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study , 1995, BMJ.

[79]  S. Gómez-Arroyo,et al.  Mutagenicity assessment of airborne particles in Mexico City , 1995 .

[80]  G. Kreutzberg,et al.  Amyloid precursor protein (APP) as a microglial acute phase protein. , 1994, Neuropathology and applied neurobiology.

[81]  G. Kreutzberg,et al.  Early and rapid de novo synthesis of Alzheimer βA4‐Amyloid precursor protein (APP) in activated microglia , 1993, Glia.

[82]  R B D'Agostino,et al.  Incidence of dementia and probable Alzheimer's disease in a general population , 1993, Neurology.

[83]  T. Molitor,et al.  Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. , 1992, Journal of immunology.

[84]  K. Boje,et al.  Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death , 1992, Brain Research.

[85]  M. Lehman,et al.  Human olfactory biopsy. The influence of age and receptor distribution. , 1992, Archives of otolaryngology--head & neck surgery.

[86]  Kevin T. Morgan Approaches to the Identification and Recording of Nasal Lesions in Toxicology Studies * , 1991, Toxicologic pathology.

[87]  V. Perry,et al.  Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain , 1990, Neuroscience.

[88]  K T Morgan,et al.  Airflow, gas deposition, and lesion distribution in the nasal passages. , 1990, Environmental health perspectives.

[89]  P. Mcgeer,et al.  Reactive microglia are positive for HLA‐DR in the substantia nigra of Parkinson's and Alzheimer's disease brains , 1988, Neurology.

[90]  M. Gimbrone,et al.  Inducible Endothelial Functions in Inflammation and Coagulation , 1987, Seminars in thrombosis and hemostasis.

[91]  S. Boland,et al.  Airborne particles evoke an inflammatory response in human airway epithelium. Activation of transcription factors , 2004, Cell Biology and Toxicology.

[92]  T. Uemura,et al.  Immunohistopathology of variations of human olfactory mucosa , 2004, European Archives of Oto-Rhino-Laryngology.

[93]  R. Devlin,et al.  Ultrastructural nasal pathology in children chronically and sequentially exposed to air pollutants. , 2001, American journal of respiratory cell and molecular biology.

[94]  C. J. Chung,et al.  Canines as sentinel species for assessing chronic exposures to air pollutants: part 1. Respiratory pathology. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[95]  S. Heck,et al.  The female sex hormone oestrogen as neuroprotectant: activities at various levels. , 2000, Novartis Foundation symposium.

[96]  J. C. de la Torre Cerebral hypoperfusion, capillary degeneration, and development of Alzheimer disease. , 2000, Alzheimer disease and associated disorders.

[97]  P. Lantos,et al.  beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease. , 1999, Neuropathology and applied neurobiology.

[98]  F. Aloisi,et al.  The role of microglia and astrocytes in CNS immune surveillance and immunopathology. , 1999, Advances in experimental medicine and biology.

[99]  I. Romieu,et al.  A survey of personal exposures to benzene in Mexico City. , 1999, Archives of environmental health.

[100]  I. Rosas,et al.  Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City. , 1998, American journal of respiratory cell and molecular biology.

[101]  Brian J Cummings,et al.  The progression of beta-amyloid deposition in the frontal cortex of the aged canine. , 1997, Brain research.

[102]  L. Calderón-Garcidueñas,et al.  DNA damage in nasal respiratory epithelium from children exposed to urban pollution , 1997, Environmental and molecular mutagenesis.

[103]  W. Bennett,et al.  Extrathoracic deposition of inhaled, coarse particles (4.5 μm) in children VS adults , 1997 .

[104]  A. Tröster,et al.  Risk factors for dementia in Parkinson's disease: effect of education. , 1996, Neuroepidemiology.

[105]  J. Geddes,et al.  Age-specific onset of beta-amyloid in beagle brains. , 1996, Neurobiology of aging.

[106]  A. Báez,et al.  Measurements of formaldehyde and acetaldehyde in the atmosphere of Mexico City. , 1995, Environmental pollution.

[107]  Brian J Cummings,et al.  Canine cognitive dysfunction as a model for human age-related cognitive decline, dementia and Alzheimer's disease: clinical presentation, cognitive testing, pathology and response to 1-deprenyl therapy. , 1995, Progress in brain research.

[108]  L. Garey,et al.  A light and electron microscopic study of HLA-DR positive cells in the human cerebral cortex and subcortical white matter. , 1995, Journal fur Hirnforschung.

[109]  Y. I. Falcón,et al.  TSP, PM10 and PM10/TSP ratios in the Mexico City Metropolitan area: a temporal and spatial approach. , 1993, Journal of exposure analysis and environmental epidemiology.

[110]  J. Lewis,et al.  Respiratory tract uptake of inhalants and metabolism of xenobiotics. , 1993, Annual review of pharmacology and toxicology.

[111]  T D Bracken,et al.  Exposure assessment for power frequency electric and magnetic fields (EMF) and its application to epidemiologic studies. , 1993, Journal of exposure analysis and environmental epidemiology.

[112]  L. Calderón-Garcidueñas,et al.  Histopathologic changes of the nasal mucosa in southwest Metropolitan Mexico City inhabitants. , 1992, The American journal of pathology.

[113]  A. Bravo,et al.  Analysis of the change in atmospheric urban formaldehyde and photochemistry activity as a result of using methyl-t-butyl-ether (MTBE) as an additive in gasolines of the metropolitan area of Mexico city , 1991 .

[114]  J. Zinkl The leukocytes. , 1981, The Veterinary clinics of North America. Small animal practice.

[115]  Walter Dandy,et al.  The Brain , 1966 .