Figure 3.

Mechanisms of air pollution-induced neuroinflammation and oxidative stress. Air pollution can cause neuroinflammation and oxidative stress through two pathways: direct and indirect. Air pollution components directly interact with the neuronal tissue in the direct pathway. This can happen by direct contact of air pollution components, such as particulate matter (PM), with the nerves in the olfactory bulb, helping them translocate deeper into the neuronal tissue. Another way is for ultrafine particles (UFP) with a diameter in the nanometer range to enter the systemic circulation after inhalation, causing disturbance of the blood–brain barrier (BBB) and reaching the cerebral tissue. The indirect pathway starts by initiating local inflammation in the lung, the first point of impact for inhaled air pollution components, which then gains systemic character. This systemic inflammation, in the form of circulating cytokines and pro-inflammatory mediators (such as tumor necrosis factor-alpha—TNFα; interleukins 1α/β and 6—IL-1α/β/6; and cyclooxygenase 2—COX-2), spreads to the brain where it promotes activation of microglia (resident macrophages). Both of these pathways result in neuroinflammation and cerebral oxidative stress, which promotes the development and progression of neurodegenerative diseases. Created with BioRender.com.