Xenobiotic pulmonary exposure and systemic cardiovascular response via neurological links

The cardiovascular response to xenobiotic particle exposure has been increasingly studied over the last two decades, producing an extraordinary scope and depth of research findings. With the flourishing of nanotechnology, the term "xenobiotic particles" has expanded to encompass not only air pollution particulate matter (PM) but also anthropogenic particles, such as engineered nanomaterials (ENMs). Historically, the majority of research in these fields has focused on pulmonary exposure and the adverse physiological effects associated with a host inflammatory response or direct particle-tissue interactions. Because these hypotheses can neither account entirely for the deleterious cardiovascular effects of xenobiotic particle exposure nor their time course, the case for substantial neurological involvement is apparent. Indeed, considerable evidence suggests that not only is neural involvement a significant contributor but also a reality that needs to be investigated more thoroughly when assessing xenobiotic particle toxicities. Therefore, the scope of this review is several-fold. First, we provide a brief overview of the major anatomical components of the central and peripheral nervous systems, giving consideration to the potential biologic targets affected by inhaled particles. Second, the autonomic arcs and mechanisms that may be involved are reviewed. Third, the cardiovascular outcomes following neurological responses are discussed. Lastly, unique problems, future risks, and hurdles associated with xenobiotic particle exposure are discussed. A better understanding of these neural issues may facilitate research that in conjunction with existing research, will ultimately prevent the untoward cardiovascular outcomes associated with PM exposures and/or identify safe ENMs for the advancement of human health.