PM_2.5 exposure induces systemic inflammation and oxidative stress in an intracranial atherosclerosis rat model

Exposure to airborne particle (PM_2.5 ) is a risk factor for intracranial atherosclerosis (ICA). Because of the established role of systemic inflammation and oxidative stress by PM_2.5 , we determined whether these processes account for PM_2.5 -mediated ICA, and also whether omega-3 fatty acid (O3FA) dietary supplementation could attenuate them.

Adult Sprague-Dawley rats were exposed to filtered air (FA) or PM_2.5 and fed either a normal chow diet (NCD) or a high-cholesterol diet (HCD), administered with or without O3FA (5 mg/kg/day by gavage) for 12 weeks. The lumen and thickness of the middle cerebral artery (MCA) were assessed. Serum tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL-1β), and interferon gamma (IFN-γ) were detected by ELISA. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) activity, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, mRNA levels of Nrf2, HO-1, NQO-1, and protein level of NOX subunit gp91 were quantified to determine the oxidative profile of brain vessels.

PM_2.5 increased (P < .05) ICA, especially in the HCD group; elevated serum TNF-α, IL-6, IL-1β, and IFN-γ; increased cerebrovascular ROS, MDA, NOX activity, and gp91 protein levels; and decreased cerebrovascular SOD activity. Nrf2, HO-1, and NQO-1 mRNA levels were upregulated (P < .05) by PM_2.5 exposure, especially in the HCD group. O3FA attenuated (P < .05) PM_2.5 -induced systemic inflammation, vascular oxidative injury, and ICA.

PM_2.5 exposure induced systemic inflammation, cerebrovascular oxidative injury, and ICA in rats with HCD. O3FA prevented ICA development, and may therefore exert a protective effect against the atherogenic potential of PM_2.5 .