International Leibniz Research Project

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Project title:
AIR pollutants and Brain Aging research Group

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since 2012


Project leader:
Dr. Roel Schins

Cooperation partner:
Prof. Dr. Flemming Cassee - National Institute for Public Health and the Environment (RIVM, in Bilthoven, The Netherlands


It is nowadays widely accepted that inhalation exposure to ambient particulate matter (PM), and specifically the fraction of nanosized particles (NP) (<100 nm) within this mixture, is related to various diseases of the respiratory tract as well as the cardiovascular system. In more recent years there has also been a growing concern about the potential toxicity of PM and nanoparticles to the human central nervous system. Early clues for a potential effect of ambient PM on neuropathology came from post-mortem human brain tissue from highly polluted areas that displayed clear signs of oxidative stress, inflammation and hallmarks of Alzheimer’s and Parkinson’s disease. Toxicological studies in rodents have revealed that indeed air pollution originating from combustion derived processes (like diesel engine exhaust) may cause neurotoxic and neurodegenerative effects (e.g. inflammation, oxidative stress, neural damage and neural cell loss). Past and ongoing studies performed at the IUF have contributed to this knowledge and have helped to increase our understanding of the underlying cellular and molecular mechanisms that drive these diseases. This includes a major finding in the field of air pollution-related health effects that came from an epidemiological study carried out by the IUF (Ranft et al. Env Res 2009) in which an association was found between exposure to traffic-rich PM and mild cognitive impairment or MCI. MCI is often considered a pre-phase of neurodegenerative diseases and Alzheimer’s disease in particular. Around the same time, cooperative research of the IUF with the RIVM demonstrated that short-term exposure to diesel engine exhaust triggers oxidative stress and inflammation in specific rat brain regions (Van Berlo et al. Arch Toxicol 2010; Gerlofs-Nijland et al., Part Fibre Toxicol 2010). Altogether, this led in 2012 to the initiation of the research project AIRBAG in which the IUF joined forces with the Dutch National Institute for Public Health and the Environment (RIVM). At the IUF Dr. Roel Schins leads this project, while coordination at the RIVM is by Prof. Dr. Flemming Cassee. As part of AIRBAG, neurotoxicologist and IUF employee Dr. Harm Heusinkveld has been placed at the RIVM. Thus, expertises from both institutes in the field of nanotoxicology, neurotoxicology and inhalation toxicology are combined.

Project description

In the AIRBAG project we aim to investigate the mechanisms whereby ambient particulate matter and nanoparticles can cause or accelerate neurotoxic and neurodegenerative effects in the brain and to instigate new research in this field. This will be done by collection and analysis of rodent brain tissue from relevant ongoing studies with different types of nano-sized particles. Parallel, we will apply in vitro approaches to identify cellular and molecular pathways of toxicity and aid to the development of 3R alternative testing strategies for neurotoxicity testing of nanoparticles.

The AIRBAG acronym (AIR pollutants and Brain Aging research Group) refers to: (1) traffic as major (nano)particle source in urban environments, (2) the lung as principle entrance route of particulate toxicants, and (3) an obvious example of a successful "health protection device", thus reflecting the long-term goals, i.e. to identify strategies and tools to protect individuals from particle-induced diseases.


Hullmann M, Albrecht C, van Berlo D, Gerlofs-Nijland ME, Wahle T, Boots AW, Krutmann J, Cassee FR, Bayer TA, Schins RPF: Diesel engine exhaust accelerates plaque formation in a mouse model of Alzheimer’s disease. Part Fibre Toxicol 14: 35, 2017. doi: 10.1186/s12989-017-0213-5

Heusinkveld HJ, Wahle T, Campbell A, Westerink RHS, Tran L, Johnston H, Stone V, Cassee FR, Schins RPF:  Neurodegenerative and neurological disorders by small inhaled particles. NeuroToxicology 2016. doi: 10.1016/j.neuro.2016.07.007

Van Berlo D*, Hullmann M*, Wessels A, Scherbart AM, Cassee FR, Gerlofs-Nijland ME, Albrecht C, Schins RPF. Investigation of the effects of short-term inhalation of carbon nanoparticles on brains and lungs of C57BL/6J and p47phox-/- mice. Neurotoxicology 43: 65-72, 2014.
doi: 10.1016/j.neuro.2014.04.008 (* equal contribution)

Hellack B, Yang A, Cassee FR, Janssen NAH, Schins RPF, Kuhlbusch TAJ:  Intrinsic hydroxyl radical generation measurements directly from sampled filters as a metric for the oxidative potential of ambient particulate matter. J Aerosol Sci 72, 47-55, 2014.
doi: 10.1016/j.jaerosci.2014.02.003

Gerlofs-Nijland ME, van Berlo D, Cassee FR, Schins RPF, Wang K and Campbell A: Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain. Part Fibre Toxicol 7: 12, 2010. doi: 10.1186/1743-8977-7-12

van Berlo D, Albrecht C, Knaapen AM, Cassee FR, Gerlofs-Nijland ME, Kooter IM, Palomero-Galagher N, Bidmon HJ, van Schooten FJ, Krutmann J and Schins RPF: Comparative evaluation of the effects of short-term inhalation exposure to diesel enginge exhaust on rat lung and brain. Arch Toxicol 84(7): 553-562, 2010. doi: 10.1007/s00204-010-0551-7