Air pollution has been shown to have a negative effect on the prognosis of ischemic stroke, or stroke caused by reduced blood flow to the brain, but the exact mechanism is unknown. A team of researchers recently conducted a study to determine whether or not increased inflammation of the brain, also known as neuroinflammation, is the main culprit.
The team published their findings in the February 16, 2023 issue of Particle and Fibre Toxicology.
Mice exposed intranasally to urban aerosols from Beijing, China, for one week demonstrated increased neuroinflammation and worsening movement disorder after ischemic stroke, compared to control mice that were not exposed to air pollution. Additionally, this effect was not observed in urban-aerosol treated mice lacking a receptor for chemicals released by the burning of fossil fuels, wood, garbage and tobacco, called polycyclic aromatic hydrocarbons (PAH). This suggests that PAHs are involved in both neuroinflammation and increased movement disorder associated with air pollution exposure in ischemic stroke.
“We designed this study to determine the effects of air pollution on disorders in the central nervous system,” said Yasuhiro Ishihara, senior author of the research paper and professor in the Graduate School of Integrated Sciences for Life at Hiroshima University. “Our narrower focus was to determine whether or not the prognosis of ischemic stroke was affected by air pollution,” said Ishihara.
The group went one step further by identifying specific components of air pollution that may directly contribute to lower prognoses in ischemic stroke.
They found evidence that intranasal exposure to air pollution from Beijing, China, increased neuroinflammation after ischemic stroke in mice through activation of microglial cells, which are immune cells found in the brain. Movement disorder was also negatively impacted in ischemic stroke mice exposed to the same air pollution. A second set of experiments replacing Beijing air pollution with PM2.5 (tiny, aerosolized particles of air pollution that are 2.5 microbes in width or less) from Yokohama, Japan demonstrated similar results, suggesting the PM2.5 fraction of urban air pollution contains the chemical responsible for increased neuroinflammation and decreased ischemic stroke prognosis.
In order to identify chemicals in air pollution responsible for decreased ischemic stroke prognosis, the research team used a mouse that lacked the aryl hydrocarbon receptor, a receptor that is activated by the presence of PAHs, to determine whether or not exposure to the Beijing air pollution would have the similar effect on mice without working aryl hydrocarbon receptors. Mice lacking the aryl hydrocarbon receptor demonstrated lower microglial cell activation and movement disorder compared to normal mice, suggesting that the PAHs present in Beijing air pollution are responsible for at least some of the neuroinflammation and lower prognosis seen in ischemic stroke mice exposed to air pollution.
Ultimately, the goal of the research team is to better understand the mechanism by which PM2.5 causes neuroinflammation, since air pollution is inhaled first into the respiratory tract. “Can small particles move from the nose to the brain? Does lung or systemic inflammation affect the brain immune system?” said Ishihara.
##
Other contributors include Nami Ishihara and Ami Oguro from the Program for Biomedical Science in the Graduate School of Integrated Sciences for Life at Hiroshima University in Higashi-Hiroshima, Japan; Miki Tanaka from Program for Biomedical Science in the Graduate School of Integrated Sciences for Life at Hiroshima University and the Laboratory for Pharmacotherapy and Experimental Neurology in the Kagawa School of Pharmaceutical Sciences at Tokushima Bunri University in Sanuki, Japan; Kouichi Itoh from the Laboratory for Pharmacotherapy and Experimental Neurology in the Kagawa School of Pharmaceutical Sciences at Tokushima Bunri University; Tomoaki Okuda from the Faculty of Science and Technology at Keio University in Yokohama, Japan; Yoshiaki Fujii-Kuriyama from the Medical Research Institute in Molecular Epidemiology at the Tokyo Medical and Dental University in Tokyo, Japan; Yu Nabetani from the Department of Applied Chemistry in the Faculty of Engineering at the University of Miyazaki in Miyazaki, Japan; Megumi Yamamoto from the Department of Environment and Public Health at the National Institute of Minamata Disease in Minamata, Japan; Christoph F. A. Vogel from the Department of Environmental Toxicology and the Center for Health and the Environment at the University of California Davis in Davis, California.
This work was supported by Research Fellowships for Young Scientists (Grant Number 20J10103), KAKENHI Grants from the Japan Society for the Promotion of Science (Grant Numbers 21K06702, 20H04341, 17H04714, 15KK0024), the Environmental Research and Technology Development Funds of the Environmental Restoration and Conservation Agency of Japan (Grant Numbers JPMEERF20165051 and JPMEERF20205007) and the National Institute of Environmental Health Sciences (Grant Numbers R01ES029126 and R01ES032827).
About Hiroshima University
Since its foundation in 1949, Hiroshima University has striven to become one of the most prominent and comprehensive universities in Japan for the promotion and development of scholarship and education. Consisting of 12 schools for undergraduate level and 5 graduate schools, ranging from natural sciences to humanities and social sciences, the university has grown into one of the most distinguished comprehensive research universities in Japan. English website: https://www.hiroshima-u.ac.jp/en
