Abstract
Traffic-generated air pollutants have been correlated with alterations in blood-brain barrier (BBB) integrity, which is associated with pathologies in the central nervous system (CNS). Much of the existing literature investigating the effects of air pollution in the CNS has predominately been reported in males, with little known regarding the effects in females. As such, this study characterized the effects of inhalation exposure to mixed vehicle emissions (MVE), as well as the presence of female sex hormones, in the CNS of female ApoE-/- mice, which included cohorts of both ovariectomized (ov-) and ovary-intact (ov+) mice. Ov + and ov- were placed on a high-fat diet and randomly grouped to be exposed to either filtered-air (FA) or MVE (200 PM/m3: 50 μg PM/m3 gasoline engine + 150 μg PM/m3 from diesel engine emissions) for 6 h/d, 7d/wk, for 30d. MVE-exposure resulted in altered cerebral microvascular integrity and permeability, as determined by the decreased immunofluorescent expression of tight junction (TJ) proteins, occludin, and claudin-5, and increased IgG extravasation into the cerebral parenchyma, compared to FA controls, regardless of ovary status. Associated with the altered cerebral microvascular integrity, we also observed an increase in matrix metalloproteinases (MMPs) -2/9 activity in the MVE ov+, MVE ov-, and FA ov- groups, compared to FA ov+. There was also elevated expression of intracellular adhesion molecule (ICAM)-1, inflammatory interleukins (IL-1, IL-1β), and tumor necrosis factor (TNF-α) mRNA in the cerebrum of MVE ov + and MVE ov- animals. IκB kinase (IKK) subunits IKKα and IKKβ mRNA expressions were upregulated in the cerebrum of MVE ov- and FA ov- mice. Our findings indicate that MVE exposure mediates altered integrity of the cerebral microvasculature correlated with increased MMP-2/9 activity and inflammatory signaling, regardless of female hormones present.