Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion

Abstract

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations.

Long-term exposure to particulate matter and risk of dementia in Korea: A national population-based cohort study

“…Air pollution does not reach the brain but adversely affects cognitive function owing to the negative effects of cardiovascular disease (Grande et al 2020;Qiu and Fratiglioni 2015). In animals, exposure to nanoparticles aggravates white matter hypoperfusion and worsens blood-brain barrier (BBB) permeability, thereby inducing cerebrovascular pathologies associated with dementia (Huuskonen et al 2021). Vascular dementia and other types of dementia such as Alzheimer's disease have different etiological features.…”

Effects of short-term waterfall forest aerosol air exposure on rat lung proteomics

“…In addition, PM2.5 can absorb a large amount of heavy metal, polycyclic aromatic hydrocarbons, and other harmful chemicals on its surface. It can enter the deep lung tissues with breathing, and the water-soluble components or insoluble nanoparticles it carries can reach other extra-pulmonary organs through blood circulation via capillaries in the lungs (17)(18)(19). Epidemiological reports have shown that for every 10 µg/m 2 increase in PM2.5 in the real environment, there is an 11% increase in cardiovascular disease-related mortality in the exposed population (20).…”

A brief overview of a mouse model of cerebral hypoperfusion by bilateral carotid artery stenosis

“…However, the 0.16 mm micro-coils would cause significant gray matter changes and a high mortality rate (75% in 14 days after surgery) compared to 0.18 mm micro-coils (the average mortality rate with 0.18 mm coils is 12.4% (0%–29.2%). 12,36,48,54–67 On the other hand, the larger sizes of micro-coils (>0.20 mm inner diameter) may not properly induce prolonged cerebral hypoperfusion. 12 Therefore, when we use other sizes of micro-coils than 0.18 mm micro-coils, we should carefully check CBF after BCAS operation.…”

“…Cerebral blood flow (CBF) after BCAS have been measured by multiple techniques, and in this section, we introduce CBF changes after BCAS operation (Table 3). 12,13,23,24,28–31,33,34,38,48,50,55–57,61,62,64,66,68–89 Laser doppler flowmetry (LDF) and laser speckle imaging (LSI) are the most widely used method for assessing CBF in BCAS mice. The relative CBF of the cortex can be measured by LDF.…”