ARB Research Seminar
This page updated July 9, 2014
Do Inhaled Ambient Particles Induce Oxidative Stress and Inflammation in the Brain?
Michael T. Kleinman, Ph.D., Department of Medicine, University of California, Irvine
July 15, 2014
Cal EPA Headquarters, 1001 "I" Street, Sacramento, CA
Numerous epidemiological and toxicological studies have demonstrated that exposure to ambient PM is associated with increased heart and lung disease and death; however, little is known about the effects of PM exposure on the central nervous system. This study took advantage of a multicity project sponsored by the Health Effects Institute to compare central nervous system impacts among sites with different source contributions to ambient PM. Brain tissue from transgenic mice exposed for 6 months to concentrated ambient fine particles (CAPs) in cities with very different pollutant source profiles was examined. The study demonstrated that exposure to CAPs from these locations could induce inflammatory changes and oxidative stress in these mice. Exposures were performed in New York, NY (NY), Sterling Forest, NY (SF), Lansing MI (MSU), Seattle, WA (SEA) and Irvine, CA (UCI).
While significant effects related to inflammatory changes were observed in brain tissue from mice exposed in most of the cities, there were site-specific variations that could be related to seasonal or compositional differences. In addition, susceptibility to inflammatory effects was found to vary across different regions of the brain, which seemed to be influenced by the levels of the protein NFκB.
Oxidative changes in the brain were also examined and were observed in mice exposed at SEA and UCI but not in mice exposed at MSU. The sources of PM at the UCI and SEA sites were more influenced by emissions related to fuel combustion (such as motor vehicles, power generation, space heating) than was the PM at the MSU site, as evidenced by a high correlation of PM concentrations with the concentrations of Ni and V in the particles at UCI and SEA but not at MSU. The concentrations of Ni and V in these exposure atmospheres were probably too low to be directly toxic; instead it is possible that these elements were acting as tracers or surrogates for oil combustion aerosols. Taken together, the results show that both inflammatory and oxidative changes can be observed in brain tissue from transgenic mice exposed to CAPs, and that effects may differ between geographic regions.
Michael T. Kleinman, Ph.D., is a Professor and Co-Director of the Air Pollution Health Effects Laboratory in the Department of Medicine at the University of California, Irvine. Prior to joining the faculty at UCI in 1982, he directed the Aerosol Exposure and Analytical Laboratory at Rancho Los Amigos Hospital in Downey, California. Dr. Kleinman's current research has focused on toxicological studies of airborne contaminants using laboratory animals. Professor Kleinman has published more than 100 articles in peer-reviewed journals dealing with the uptake and dosimetry of inhaled pollutants, cardiopulmonary and immunological responses associated with inhalation of PM2.5, health effects of acidic and non-acidic aerosols, and studies of the effects of mixtures of particles with other pollutants such as ozone, formaldehyde, sulfur dioxide, and nitrogen dioxide. Dr. Kleinman's previous studies examined cardiopulmonary effects of concentrated ambient ultrafine, fine and coarse particles using animal models of susceptible human populations. His current studies address the role of organic and inorganic constituents of air pollution mixtures in the development or exacerbation of heart disease. Dr. Kleinman has been studying the health effects of exposures to particles and gases found in ambient air for more than 30 years.
Dr. Kleinman is a consultant to the U.S. EPA Science Advisory Board and a member of the Board of Scientific Counselors for the Center of Disease Control and Prevention (CDC-ATSDR/NCEH). Professor Kleinman is Chairman of the State of California's Scientific Review Panel on Toxic Air Contaminants. In addition Dr. Kleinman also serves as Chairman of the Air Quality Advisory Committee, which reviews California's air quality criteria documents. Professor Kleinman holds a M.S. in Chemistry from the Polytechnic Institute of Brooklyn and a Ph.D. in Environmental Health Sciences from New York University.