Abstract
Exposure to ambient air pollution has been consistently associated with respiratory and cardiovascular disease. However, the neurological effects of air pollution have received little attention. It is suggested that the components of air pollution, such as particulate matter (PM) and specifically ultrafine particulate matter (UFP), may have the potential to extend beyond pulmonary organs to the central nervous system (CNS) and, ultimately, the brain. The transport mechanisms are not clear, although at least four possible routes have been proposed implicating PM and UFP in neurological disease processes. A limited number of studies have been undertaken to assess the role of PM and UFP in CNS diseases, including migraine, headache, stroke, Alzheimer’s disease, and Parkinson’s disease. Considering the high prevalence of such CNS diseases, along with the frequent and increasing exposure to ambient air pollution, it is important to highlight possible associations with regards to preventative, monitoring, and control measures. This article aimed to review the literature in relation to translocation routes of PM and UFP and their potential role in neurological disease processes.
About the authors
Clare Loane (BSc, MSc) is a psychologist by background, receiving her education from the University of Surrey and University College London. She is involved in a number of neuroimaging studies using fMRI and PET focusing on the pathophysiology and functional anatomy of neurodegenerative disease. She is currently completing her PhD in Neuroscience at Imperial College London.
Dr. Christodoulos Pilinis, Professor, is the Dean of the School of Environment of the University of the Aegean and the Director of the Water and Air Quality Laboratory of the Department of the Environment of the same University. He has 25 years of experience in atmospheric aerosol related research, both in Europe and the USA. He has published several papers focused on the processes that affect the size distribution and chemical composition of atmospheric aerosols. He is also interested in investigating how air quality affects visibility degradation and the climate.
Themistokles Lekkas is Professor (e) of Environmental Engineering of the Environmental Science Department, University of Aegean. He is a graduate of Chemical Engineering from the NTU of Athens and holds a MSc (Mark of Distinction) and a PhD from the Imperial College, London. He has extensive industrial experience and has held various managerial positions and is the founder of the Global Nest Journal. Professor Lekkas has conducted extensive research and has published research papers in the areas of water filtration, fluidization, disinfection by-products, priority substances, emerging pollution and solid waste management.
Marios Politis (MD, MSc, DIC, PhD) is a Clinical Lecturer in Neurology within the Department of Medicine at Imperial College London. He graduated in Medicine from the University of Athens, Greece. He obtained an MSc degree and the Diploma of Imperial College in Integrative Neuroscience. He holds a PhD in Clinical Neuroscience from Imperial College London and has worked in clinical research for the past 10 years. He has achieved a number of awards and distinctions and has contributed to the teaching and training of undergraduate and postgraduate students. He is an active member of American Academy of Neurology, Movement Disorder Society, British Neuroscience Association, European Multiple System Atrophy Study Group and a Fellow of Royal Society of Medicine. His research interests include the use of functional imaging in Movement Disorders and Multiple Sclerosis as a method of investigating aetiology, pathophysiology, and effects and complications of neuroprotective and neurorestorative therapies.
References
Akmoto, H. (2003). Global air quality and pollution. Science 5, 1716–1719.10.1126/science.1092666Search in Google Scholar
Andersen, Z.J., Olsen, T.S., Andersen, K.K., Loft, S., Ketzel, M., and Raaschou-Nielsen, O. (2010). Association between short-term exposure to ultrafine particles and hospital admissions for stroke in Copenhagen, Denmark. Eur. Heart J. 31, 2034–2040.10.1093/eurheartj/ehq188Search in Google Scholar
Arulmozhi, D.K., Veeranjaneyulu, A., and Bodhankar, S.L. (2005). Migraine: current concepts and emerging therapies. Vascul. Pharmacol. 43, 176–187.10.1016/j.vph.2005.07.001Search in Google Scholar
Bernal-Pacheco, O. and Román, G.C. (2007). Environmental vascular risk factors: new perspectives for stroke prevention. Neurol. Sci. 262, 60–70.10.1016/j.jns.2007.06.026Search in Google Scholar
Block, M.L. and Hong, J.S. (2005). Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog. Neurobiol. 76, 77–98.10.1016/j.pneurobio.2005.06.004Search in Google Scholar
Block, M.L., Wu, X., Pei, Z., Li, G., Wang, T., Qin, L., Wilson, B., Yang, J., Hong, J.S., and Veronesi B. (2004). Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase. FASEB J. 18, 1618–1620.10.1096/fj.04-1945fjeSearch in Google Scholar
Block, M.L., Zecca, L., and Hong, J.S. (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8, 57–69.10.1038/nrn2038Search in Google Scholar
Bodian, D. and Howe, H.A. (1941). The rate of progression of polio myelitis virus in nerves. Bull. Johns Hopkins Hosp. 69, 79–85.Search in Google Scholar
Brook, R.D. (2008). Air pollution: what is bad for the arteries might be bad for the veins. Arch. Intern. Med. 168, 909–911.10.1001/archinte.168.9.909Search in Google Scholar
Brook, R.D., Franklin, B., Cascio, W., Hong, Y., Howard, G., Lipsett, M., Luepke, R., Mittleman, M., Samet, J., Smith, S.C., et al. (2004). Expert Panel on Population and Prevention Science of the American Heart Association. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 109, 2655–2671.10.1161/01.CIR.0000128587.30041.C8Search in Google Scholar
Brunekreef, B. and Holgate, S.T. (2002). Air pollution and health. Lancet 19, 1233–1242.10.1016/S0140-6736(02)11274-8Search in Google Scholar
Calderón-Garcidueñas, L., Azzarelli, B., Acuna, H., Garcia, R., Gambling, T.M., Osnaya, N., Monroy, S., Del Tizapantzi, M.R., Carson, J.L., Villarreal-Calderon, A., et al. (2002). Air pollution and brain damage. Toxicol. Pathol. 30, 373–389.10.1080/01926230252929954Search in Google Scholar PubMed
Calderón-Garcidueñas, L., Reed, W., Maronpot, R.R., Henríquez-Roldán, C., Delgado-Chavez, R., Calderón-Garcidueñas, A., Dragustinovis, I., Franco-Lira, M., Aragón-Flores, M., Solt, A.C., et al. (2004). Brain inflammation and Alzheimer’s-like pathology in individuals exposed to severe air pollution. Toxicol. Pathol. 32, 650–658.10.1080/01926230490520232Search in Google Scholar PubMed
Calderón-Garcidueñas, L., Solt, A.C., Henríquez-Roldán, C., Torres-Jardón, R., Nuse, B., Herritt, L., Villarreal-Calderón R., Osnaya N., Stone I., García R., et al. (2008a). Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid β-42 and α-synuclein in children and young adults. Toxicol. Pathol. 36, 289–310.10.1177/0192623307313011Search in Google Scholar PubMed
Calderón-Garcidueñas, L., Mora-Tiscareño, A., Ontiveros, E., Gómez-Garza, G., Barragán-Mejía, G., Broadway, J., Chapman, S., Valencia-Salazar, G., Jewells, V., Maronpot, R.R., et al. (2008b). Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn. 68, 117–127.10.1016/j.bandc.2008.04.008Search in Google Scholar PubMed
Calderón-Garcidueñas, L., Franco-Lira, M., Henríquez-Roldán, C., Osnaya, N., González-Maciel, A., Reynoso-Robles, R., Villarreal-Calderon, R., Herritt, L., Brooks, D., Keefe, S., et al. (2010). Urban air pollution: influences on olfactory function and pathology in exposed children and young adults. Exp. Toxicol. Pathol. 62, 91–102.10.1016/j.etp.2009.02.117Search in Google Scholar PubMed PubMed Central
Carson, A.P., Rose, K.M., Sanford, C.P., Ephross, S.A., Stang, P.E., Hunt, K.J., Brown, C.A., and Szklo, M. (2004). Lifetime prevalence of migraine and other headaches lasting 4 or more hours: the Atherosclerosis Risk in Communities (ARIC) study. Headache 44, 20–28.10.1111/j.1526-4610.2004.04005.xSearch in Google Scholar PubMed
Cedervall, T., Lynch, I., Foy, M., Berggård, T., Donnelly, S.C., Cagney, G., Linse, S., and Dawson, K.A. (2007). Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. Chem. Int. Ed. Engl. 46, 5754–5756.10.1002/anie.200700465Search in Google Scholar PubMed
Colvin, V.L. and Kulinowski, K.M. (2007). Nanoparticles as catalysts for protein fibrillation. Proc. Natl. Acad. Sci. USA 104, 8679–8680.10.1073/pnas.0703194104Search in Google Scholar PubMed PubMed Central
Czerniawska, A. (1970). Experimental investigations on the penetration of 198Au from nasal mucous membrane into cerebrospinal fluid. Acta Otolaryngol. 70, 58–61.10.3109/00016487009181859Search in Google Scholar PubMed
Dales, R.E., Cakmak, S., and Vidal, C.B. (2009). Air pollution and hospitalization for headache in Chile. Am. J. Epidemiol. 170, 1057–1066.10.1093/aje/kwp217Search in Google Scholar PubMed PubMed Central
De Lorenzo, A.J.D. (1970). The olfactory neuron and the blood-brain barrier. Taste and smell in vertebrates. CIBA Foundation Symposium Series. G.E.W. Wolstenholme and J. Knight, eds. (London: J & A Churchill), pp. 151–176.10.1002/9780470715369.ch9Search in Google Scholar
Doty, R.L. (2008). The olfactory vector hypothesis of neurodegenerative disease: is it viable? Ann. Neurol. 63, 7–15.10.1002/ana.21327Search in Google Scholar
Edwards, R.D., Liu, Y., He, G., Yin, Z., Sinton, J., Peabody, J., and Smith, K.R. (2007). Household CO and PM measured as part of a review of China’s National Improved Stove Program. Indoor Air 17, 189–203.10.1111/j.1600-0668.2007.00465.xSearch in Google Scholar
Ehrenberg, M. and McGrath, J.L. (2005). Binding between particles and proteins in extracts: implications for microrheology and toxicity. Acta Biomater. 1, 305–315.10.1016/j.actbio.2005.02.002Search in Google Scholar
Elder, A. and Oberdörster, G. (2006). Translocation and effects of ultrafine particles outside of the lung. Clin. Occup. Environ. Med. 5, 785–796.Search in Google Scholar
Faber, H.K. (1938). The early lesions of poliomyelitis after intranasal inoculation. J. Pediatr. 13, 10–37.10.1016/S0022-3476(38)80126-8Search in Google Scholar
Freire, C., Ramos, R., Puertas, R., Lopez-Espinosa, M.J., Julvez, J., Aguilera, I., Cruz, F., Fernandez, M.F., Sunyer, J., and Olea, N. (2010). Association of traffic-related air pollution with cognitive development in children. J. Epidemiol. Community. Health 64, 223–228.10.1136/jech.2008.084574Search in Google Scholar
Geiser, M., Schurch, S., and Gehr, P. (2003). Influence of surface chemistry and topography of particles on their immersion into the lung’s surface-lining layer. J. Appl. Physiol. 94, 1793–1801.10.1152/japplphysiol.00514.2002Search in Google Scholar
Gerlofs-Nijland, M.E., van Berlo, D., Cassee, F.R., Schins, R.P., Wang, K., and Campbell, A. (2010). Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain. Part. Fibre Toxicol. 17, 7–12.10.1186/1743-8977-7-12Search in Google Scholar
Gluckman, P.D. and Hanson, M.A. (2004). Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr. Res. 56, 311–317.10.1203/01.PDR.0000135998.08025.FBSearch in Google Scholar
Grandjean, P. and Landrigan, P.J. (2006). Developmental neurotoxicity of industrial chemicals. Lancet 368, 2167–2178.10.1016/S0140-6736(06)69665-7Search in Google Scholar
Headache classification subcommittee of the International Headache Society. (2004). The International Classification of Headache Disorders. 2nd edition. Cephalalgia 24(Suppl 1), 9–160.Search in Google Scholar
Henriksson, J. and Tjälve, H. (2000). Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes. Toxicol. Sci. 55, 392–398.10.1093/toxsci/55.2.392Search in Google Scholar PubMed
Henrotin, J.B., Besancenot, J.P., Bejot, Y., and Giroud, M. (2007). Short-term effects of ozone air pollution on ischaemic stroke occurrence: a case-crossover analysis from a 10-year population-based study in Dijon, France. Occup. Environ. Med. 64, 439–445.10.1136/oem.2006.029306Search in Google Scholar PubMed PubMed Central
Howe, H.A. and Bodian, D. (1941). Poliomyelitis in the chimpanzee: a clinical-pathological study. Bull. Johns Hopkins Hosp. 2, 149–182.Search in Google Scholar
Hunter, D.D. and Undem, B.J. (1999). Identification and substance P content of vagal afferent neurons innervating the epithelium of the guinea pig trachea. Am. J. Respir. Crit. Care Med. 159, 1943–1948.10.1164/ajrccm.159.6.9808078Search in Google Scholar PubMed
Joubert, J., Cumming, T.B., and McLean, A.J. (2007). Diversity of risk factors for stroke: the putative roles and mechanisms of depression and air pollution. J. Neurol. Sci. 262, 71–76.10.1016/j.jns.2007.06.027Search in Google Scholar PubMed
Kettunen, J., Lanki, T., Tiittanen, P., Aalto, P.P., Koskentalo, T., Kulmala, M., Salomaa, V., and Pekkanen, J. (2007). Associations of fine and ultrafine particulate air pollution with stroke mortality in an area of low air pollution levels. J. Stroke 38, 918–922.10.1161/01.STR.0000257999.49706.3bSearch in Google Scholar PubMed
Kreuter, J., Hekmatara, T., Dreis, S., Vogel, T., Gelperina, S., and Langer, K. (2007). Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain. J. Control Release 118, 54–58.10.1016/j.jconrel.2006.12.012Search in Google Scholar PubMed
Landrigan, P.J. and Tamburlini, G. (2005). Children’s health and the environment: a transatlantic dialogue. Environ. Health Perspect. 113, 646–647.10.1289/ehp.113-a646Search in Google Scholar
Ling, Z., Zhu, Y., Tong, C., Snyder, J.A., Lipton, J.W., and Carvey, P.M. (2006). Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally. Exp. Neurol. 199, 499–512.10.1016/j.expneurol.2006.01.010Search in Google Scholar PubMed
Lipton, R.B., Stewart, W.F., Diamond, S., Diamond, M.L., and Reed, M. (2001). Prevalence and burden of migraine in the United States: Data from the American Migraine Study II. Headache 41, 646–657.10.1046/j.1526-4610.2001.041007646.xSearch in Google Scholar PubMed
Lisabeth, L.D., Escobar, J.D., Dvonch, J.T., Sánchez, B.N., Majersik, J.J., Brown, D.L., Smith, M.A., and Morgenstern, L.B. (2008). Ambient air pollution and risk for ischemic stroke and transient ischemic attack. Ann. Neurol. 64, 53–59.10.1002/ana.21403Search in Google Scholar PubMed PubMed Central
Liu, L., Guo, K., Lu, J., Venkatraman, S.S., Luo, D., Ng, K.C., Ling, E.A., Moochhala, S., and Yang, Y.Y. (2008). Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG-TAT for drug delivery across the blood-brain barrier. Biomaterials 29, 1509–1517.10.1016/j.biomaterials.2007.11.014Search in Google Scholar PubMed
Lokken, P.R., Wellenius, G.A., Coull, B.A., Burger, M.R., Schlaug, G., Suh, H.H., and Mittleman, M.A. (2008). Air pollution and risk of stroke: underestimation of effect due to misclassification of time of event onset. Epidemiology 20, 137–142.10.1097/EDE.0b013e31818ef34aSearch in Google Scholar PubMed PubMed Central
Lynch, I., Cedervall, T., Lundqvist, M., Cabaleiro-Lago, C., Linse, S., and Dawson, K.A. (2007). The nanoparticle-protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century. Adv. Colloid Interface Sci. 134–135, 167–174.10.1016/j.cis.2007.04.021Search in Google Scholar PubMed
Manousakis, G., Jensen, M.B., Chacon, M.R., Sattin, J.A., and Levine, R.L. (2009). The interface between stroke and infectious disease: infectious diseases leading to stroke and infections complicating stroke. Curr. Neurol. Neurosci. Rep. 9, 28–34.10.1007/s11910-009-0005-xSearch in Google Scholar PubMed
McGeer, P.L., Itagaki, S., Boyes, B.E., and McGeer, E.G. (1988). Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38, 1285–1291.10.1212/WNL.38.8.1285Search in Google Scholar PubMed
Migliore, L. and Coppedè, F. (2009). Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat. Res. 674, 73–78.10.1016/j.mrgentox.2008.09.013Search in Google Scholar PubMed
Mukamal, K.J., Wellenius, G.A., Suh, H.H., and Mittleman, M.A. (2009). Weather and air pollution as triggers of severe headaches. Neurology 72, 922–927.10.1212/01.wnl.0000344152.56020.94Search in Google Scholar PubMed PubMed Central
Nattero, G. and Enrico, A. (1996). Outdoor pollution and headache. Headache 36, 243–245.10.1046/j.1526-4610.1996.3604243.xSearch in Google Scholar PubMed
Ng, A.W., Bidani, A., and Heming, T.A. (2004). Innate host defense of the lung: efects of lung-lining fluid pH. Lung 182, 297–317.10.1007/s00408-004-2511-6Search in Google Scholar PubMed
Oberdörster, G., Ferin, J., and Lehnert, B.E. (1994). Correlation between particle size, in vivo particle persistence, and lung injury. Environ. Health Perspect. 102(Suppl 5), 173–179.Search in Google Scholar
Oberdörster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Lunts, A., Kreyling, W., and Cox, C. (2002). Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J. Toxicol. Environ. Health Part A 25, 1531–1543.10.1080/00984100290071658Search in Google Scholar PubMed
Oberdörster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Kreyling, W., and Cox, C. (2004). Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 16, 437–445.10.1080/08958370490439597Search in Google Scholar
Oberdörster, G., Oberdörster, E., and Oberdörster, J. (2005). Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839.10.1289/ehp.7339Search in Google Scholar
Partti-Pellinen, K., Marttila, O., Vilkka, V., Jaakkola, J.J., Jäppinen, P., and Haahtela, T. (1996). The South Karelia Air Pollution Study: effects of low-level exposure to malodorous sulfur compounds on symptoms. Arch. Environ. Health 51, 315–320.10.1080/00039896.1996.9936031Search in Google Scholar
Perera, F.P., Rauh, V., Whyatt, R.M., Tsai, W.Y., Tang, D., Diaz, D., Hoepner, L., Barr, D., Tu, Y.H., Camann, D., et al. (2006). Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children. Environ. Health Perspect. 114, 1287–1292.10.1289/ehp.9084Search in Google Scholar
Perry, V.H., Cunningham, C., and Holmes, C. (2007). Systemic infections and inflammation affect chronic neurodegeneration. Nat. Rev. Immunol. 7, 161–167.10.1038/nri2015Search in Google Scholar
Peters, A., Veronesi, B., Calderon-Garciduenas, L., Gehr, P., Chen, L.C., Geiser, M., Reed, W., Rothen-Rutishauser, B., Schürch, S., Schulz, H. (2006). Translocation and potential neurological effects of fine and ultrafine particles. A critical update. Part. Fibre Toxicol. 8, 3–13.Search in Google Scholar
Prince, P.B., Rapoport, A.M., Sheftell, F.D., Tepper, S.J., and Bigal, M.E. (2004). The effect of weather on headache. Headache 44, 596–602.10.1111/j.1526-4610.2004.446008.xSearch in Google Scholar
Qin, L., Wu, X., Block, M.L., Liu, Y., Breese, G.R., Hong, J.S., Knapp, D.J., and Crews, F.T. (2007). Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55, 453–462.10.1002/glia.20467Search in Google Scholar
Ranft, U., Schikowski, T., Sugiri, D., Krutmann, J., and Krämer, U. (2009). Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environ. Res. 109, 1004–1011.10.1016/j.envres.2009.08.003Search in Google Scholar
Rasmussen, B.K. (1999). Epidemiology and socio-economic impact of headache. Cephalalgia 25, 20–23.10.1177/0333102499019S2505Search in Google Scholar
Rasmussen, B.K., Jensen, R., Schroll, M., and Olesen, J. (1991). Epidemiology of headache in a general population—A prevalence study. J. Clin. Epidemiol. 44, 1147–1157.10.1016/0895-4356(91)90147-2Search in Google Scholar
Rivest, S., Lacroix, S., Vallières, L., Nadeau, S., Zhang, J., and Laflamme, N. (2000). How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli. Proc. Soc. Exp. Biol. Med. 223, 22–38.10.1046/j.1525-1373.2000.22304.xSearch in Google Scholar PubMed
Schlesinger, R.B., Kunzli, N., Hidy, G.M., Gotschi, T., and Jerrett, M. (2006). The health relevance of ambient particulate matter characteristics: coherence of toxicological and epidemiological inferences. Inhal. Toxicol. 18, 95–125.10.1080/08958370500306016Search in Google Scholar PubMed
Sharma, H.S. and Johanson, C.E. (2007). Intracerebroventricularly administered neurotrophins attenuate blood cerebrospinal fluid barrier breakdown and brain pathology following whole-body hyperthermia: an experimental study in the rat using biochemical and morphological approaches. Ann. N. Y. Acad. Sci. 1122, 112–129.10.1196/annals.1403.008Search in Google Scholar PubMed
Sharma, H.S., Ali, S.F., Dong, W., Tian, Z.R., Patnaik, R., Patnaik, S., Sharma, A., Boman, A., Lek, P., Seifert, E., et al. (2007). Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord. Ann. N. Y. Acad. Sci. 1122, 197–218.10.1196/annals.1403.014Search in Google Scholar PubMed
Strøm-Tejsen, P., Weschler, C.J., Wargocki, P., Myśków, D., and Zarzycka, J. (2008). The influence of ozone on self-evaluation of symptoms in a simulated aircraft cabin. J. Expo. Sci. Environ. Epidemiol. 18, 272–281.10.1038/sj.jes.7500586Search in Google Scholar PubMed
Suglia, F.S., Gryparis, A., Wright, R.O., Schwartz, J., and Wright, R.J. (2008). Association of black carbon with cognition among children in a prospective birth cohort study. Am. J. Epidemiol. 167, 280–286.10.1093/aje/kwm308Search in Google Scholar PubMed
Szyszkowicz, M. (2008). Ambient air pollution and daily emergency department visits for headache in Ottawa, Canada. Headache 48, 1076–1081.10.1111/j.1526-4610.2007.01039.xSearch in Google Scholar PubMed
Szyszkowicz, M., Stieb, D.M., and Rowe, B.H. (2009). Air pollution and daily ED visits for migraine and headache in Edmonton, Canada. Am. J. Emerg. Med. 27, 391–396.10.1016/j.ajem.2008.03.013Search in Google Scholar PubMed
Takenaka, S., Karg, E., Roth, C., Schulz, H., Ziesenis, A., Heinzmann, U., Schramel, P., and Heyder, J. (2001). Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats Environ. Health Perspect. 109, 547–551.Search in Google Scholar
Thomas, B. and Beal, M.F. (2007). Parkinson’s disease. Hum. Mol. Genet. 16, 183–194.10.1093/hmg/ddm159Search in Google Scholar PubMed
Thomson, E.M., Kumarathasan, P., Calderón-Garcidueñas, L., and Vincent, R. (2007). Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression. Environ. Res. 105, 224–233.10.1016/j.envres.2007.06.005Search in Google Scholar PubMed
Tjälve, H. and Henriksson, J. (1999). Uptake of metals in the brain via olfactory pathways. Neurotoxicology 20, 181–195.Search in Google Scholar
Tjälve, H., Mejàre, C., and Borg-Neczak, K. (1995). Uptake and transport of manganese in primary and secondary olfactory neurones in pike. Pharmacol. Toxicol. 77, 23–31.10.1111/j.1600-0773.1995.tb01909.xSearch in Google Scholar PubMed
Ueno, M., Akiguchi, I., Hosokawa, M., Kotani, H., Kanenishi, K., and Sakamoto, H. (2000). Blood-brain barrier permeability in the periventricular areas of the normal mouse brain. Acta Neuropathol. 99, 385–392.10.1007/s004010051140Search in Google Scholar PubMed
Veronesi, B., Makwana, O., Pooler, M., and Chen, LC. (2005). Effects of subchronic exposures to concentrated ambient particles. VII. Degeneration of dopaminergic neurons in Apo E-/- mice. Inhal. Toxicol. 17, 235–241.10.1080/08958370590912888Search in Google Scholar PubMed
Wang, S., Zhang, J., Zeng, X., Zeng, Y., Wang, S., and Chen, S. (2009). Association of traffic-related air pollution with children’s neurobehavioral functions in Quanzhou, China. Environ. Health Perspect. 117, 1612–1618.10.1289/ehp.0800023Search in Google Scholar PubMed PubMed Central
Wellenius, G.A., Schwartz, J., and Mittleman, M.A. (2005). Air pollution and hospital admissions for ischemic and hemorrhagic stroke among Medicare beneficiaries. Stroke 36, 2549–2553.10.1161/01.STR.0000189687.78760.47Search in Google Scholar PubMed
Wellenius, G.A., Schwartz, J., and Mittleman, M.A. (2006). Particulate air pollution and hospital admissions for congestive heart failure in seven United States cities. Am. J. Cardiol. 97, 404–408.10.1016/j.amjcard.2005.08.061Search in Google Scholar PubMed
Wimo, A., Jonsson, L., and Winblad, B. (2006). An estimate of the worldwide prevalence and direct costs of dementia in 2003. Dement. Geriatr. Cogn. Disord. 21, 175–181.10.1159/000090733Search in Google Scholar PubMed
World Health Organization (2000). Air quality guidelines for Europe, 2nd Edition. WHO Regional Publications, European Series, No. 91.Search in Google Scholar
Xie, J., Fan, R., and Meng, Z. (2007). Protein oxidation and DNA-protein crosslink induced by sulfur dioxide in lungs, livers, and hearts from mice. Inhal. Toxicol. 19, 759–765.10.1080/08958370701399885Search in Google Scholar PubMed
Zhang, Z.F., Yu, S.Z., and Zhou GD. (1988). Indoor coal fumes as a risk factor of stroke, Shanghai. Am. J. Publ. Health 78, 975–977.10.2105/AJPH.78.8.975Search in Google Scholar PubMed PubMed Central
Zhang, Q.Z., Zha, L.S., Zhang, Y., Jiang, W.M., Lu, W., Shi, Z.Q., Jiang X.G., and Fu, S.K. (2006). The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats. J. Drug Target. 14, 281–290.10.1080/10611860600721051Search in Google Scholar PubMed
Zhou, N.B., Fu, Z.J., and Sun, T. (2008). Effects of different concentrations of oxygen-ozone on rats’ astrocytes in vitro. Neurosci. Lett. 441, 178–182.10.1016/j.neulet.2008.06.036Search in Google Scholar PubMed
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