Enhanced Cerebral Microbleeds by Long-Term Air Pollution Exposure in Spontaneously Hypertensive Rats

ABSTRACT

Background

Cerebral microbleeds (CMBs) are associated with a high risk for stroke . The present study determined whether long-term exposure to PM2.5 results in progressive worsening of CMBs and induction of systemic inflammation and microvascular oxidative stress.

Methods

Sixteen male Spontaneously hypertensive rats (SHR) and eight Wistar-Kyoto (WKY) rats were exposed to either filtered air or PM2.5 for 12 months. To detect CMBs, rats were imaged using a 7-T MRI. To determine systemic inflammation and oxidative stress, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), as well as reactive oxygen species (ROS), NADPH activity and its subunits p22/47/67phox & gp91phox were measured.

Results

During the exposure period, the mean daily concentration of PM2.5 was 59.2 ± 1.0 μg/m³. PM2.5 exposure significantly increased the incidence of CMBs compared to the PM2.5 (-) group (37.5% vs 12.5% incidence rate, p < 0.001). Animals exposed to PM2.5 also had significantly increased systolic blood pressures (SBPs) at 3 months (173 ± 5 vs 157 ± 5 mmHg, p < 0.05), 6 months (218 ± 6 vs 193 ± 7 mmHg, p < 0.01), 9 months (222 ± 6 vs 203 ± 8 mmHg, p < 0.05), and 12 months (231 ± 4 vs 207 ± 5 mmHg, p = 0.01). Additionally, there were significant elevations in IL-6, MCP-1, and TNF-α in the exposed group. Furthermore, PM2.5 significantly increased NOX activity and protein levels of gp91phox and p22/47/67phox.

Conclusion

In the SHR model, long-term exposure to PM2.5 worsened CMBs, increased SBPs, induced systemic inflammation and oxidative stress. Therefore, PM2.5 is potentially a controllable risk factor that promotes CMBs in certain patients, such as those with hypertension.

KEYWORDS:

• PM2.5
• cerebral microbleeds
• inflammation
• ros
• nadph
• small vessel disease

Acknowledgments

This work was supported by the National Nature Science Foundation of China (No. 21707095, No. 82072549 and No. 81871838).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Innovative Research Group Project of the National Natural Science Foundation of China [82072549]; National Nature Science Foundation of China [81871838]; National Nature Science Foundation of China [21707095].

Notes on contributors

Lipeng Cai

Lipeng Cai, a researcher of China-America Institute of Neuroscience and a professor of Neurology, Beijing Luhe Hospital, Capital Medical University. She has engaged in stroke prevention and neuroprotection after stroke. In the past five years, she has published 7 SCI, which are all in mainstream academic journals exerting international influence.

Jianjie Yang

Jianjie Yang, a research associate of Pathology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.

Eric Cosky

Eric Cosky, a doctor and a researcher from the Department of Neurosurgery, Wayne State University School of Medicine (USA).

Ruiqiang Xin

Ruiqiang Xin, a professor of Medical Imaging, Beijing Luhe Hospital, Capital Medical University, Beijing, China.

Xiaokun Geng

Xiaokun Geng, a professor of Neurology, Beijing Luhe Hospital, Capital Medical University. He has engaged in neurovascular intervention and in the mechanisms of cerebral and drug protection in stroke. In the past five years, he has published more than 80 SCI, which are all in mainstream academic journals exerting international influence in his professional field.

Yuchuan Ding

Yuchuan Ding, a professor of Neurosurgery at Wayne State University School of Medicine (USA), where he is a principal investigator of the Merit Review Award (I01RX-001964-01) from the US Department of Veterans Affairs Rehabilitation R&D Service. In the past five years, he has published more than 150 SCI, which are all in mainstream academic journals exerting international influence in his professional field.