The effect of diesel exhaust exposure on blood-brain barrier integrity and function

Air pollution collectively describes the presence of a diverse and complex mixture of chemicals, particulate matter (PM), or of biological material in the ambient air which can cause harm or discomfort to humans or other living organisms [1]. Millions of people worldwide are chronically exposed to airborne pollutants in concentrations that are well above legal safety standards. Traffic intensity is one of the most important determinants of ambient anthropogenic PM concentration, and people living in cities and near major traffic routes are particularly affected by high levels of PM pollution [2, 3]. About a decade ago, the central nervous system (CNS) has also been proposed to be a target organ for the detrimental effects of airborne pollutants [4]. Emerging evidence from recent epidemiological, observational, clinical, and experimental studies suggest that certain neurological diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke, may be strongly associated with ambient air pollution. Air pollutants affect the CNS either directly by transport of nanosized particles into the CNS or secondarily through systemic inflammations. Either of the effects can be caused by the physical characteristics of the particle itself or by toxic compounds that adsorb on the particles. Although the exact mechanisms underlying brain pathology induced by air pollution are not fully understood, several lines of current evidence point out that neuroinflammation, oxidative stress, glial activation, and cerebrovascular damage might be the primary pathways activated by inhaled UFP. Aim of the study is to investigate how the exposure to diesel exhaust particles (DEP) may cause endothelial dysfunctions. Experiments were performed using hCMEC/D3 cell line (human cerebral microvascular endothelial cells) as brain-blood barrier (BBB) model. DEP doses for cell culture in vitro experiments were basically related to the human ambient exposure. To investigate alterations of t