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.
Highlights
Cerebrovascular dysfunction is associated with dementia with anatomical damage to white matter [1]
We investigate the effect of nanoparticulate matter on brain white matter pathology in a murine bilateral carotid artery stenosis (BCAS) model of chronic cerebral hypoperfusion (CCH) which has been previously shown to induce white matter injury [11]
To study the effects of combined cerebral hypoperfusion and nanoparticulate matter (nPM) exposure, mice were exposed to nPM aerosol or filtered air for 6 weeks
Summary
Cerebrovascular dysfunction is associated with dementia with anatomical damage to white matter [1]. Brain hypoperfusion is associated with multiple forms of dementia and white matter structural changes [2, 3]. PM Amplifies Hypoperfusion-Induced Vascular Pathology matter with reduced brain white matter regional volumes [4,5,6,7,8]. We investigate the effect of nanoparticulate matter (nPM, aerodynamic diameter ≤200 nm) on brain white matter pathology in a murine bilateral carotid artery stenosis (BCAS) model of chronic cerebral hypoperfusion (CCH) which has been previously shown to induce white matter injury [11]. We hypothesize that nPM exposure amplifies the effects of CCH on white matter injury and blood brain barrier (BBB) permeability
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