This smoke significantly deteriorates air quality across the country, triggering numerous health issues. While the link between wildfire smoke and cardiovascular, pulmonary, ocular, nasal, and neurological outcomes is established, the mechanisms underlying these neurological effects remain enigmatic.
Neuroinflammation and Pollutant Exposure
Emerging research has highlighted a connection between wildfire smoke exposure, neuroinflammation, and pollutants like ozone and diesel emissions. This association becomes more evident when considering acute and subchronic exposures. Neurological consequences of these exposures are hypothesized to stem from pollutants interacting with the lungs, leading to pulmonary proteolysis. Subsequently, fragmented peptides generated from this process may infiltrate the circulation and disrupt the blood-brain barrier (BBB) integrity, triggering neuroinflammatory responses.
Blood-Brain Barrier Phenotypes and Inflammatory Signaling
The BBB is a complex interface comprising endothelial cells and pericytes surrounded by astrocytic end-feet, serving to regulate CNS separation from peripheral circulation. Disturbances in the BBB can lead to neuroinflammation. Recent studies have identified two distinct populations of BBB endothelial cells marked by CD31 expression levels. Notably, a proinflammatory phenotype characterized by reduced relative CD31 is linked to inflammatory responses. In the context of wildfire smoke exposure, these responses manifest as upregulated intercellular adhesion molecule-1 (ICAM-1) and chemokine C–C motif ligand 2 (CCL2), subsequently activating astrocytes and microglia.
Neuroinflammation Resolution Dynamics
Previous research delving into a 20-day exposure to natural wildfire smoke particles showed alterations in neurovascular endothelial cell phenotypes. Specifically, the CD31Hi (anti-inflammatory) cells exhibited reduced levels of CCL2, inducible nitric oxide synthase, and tumor necrosis factor-α (TNFα). In contrast, CD31Med expressing endothelial cells showed increased expression of the same inflammatory proteins, suggesting a transition from induction to resolution of the inflammatory response.
Peripheral Immune Responses and Transmigration Signals
Understanding Neuroinflammation Dynamics
Prior studies have highlighted the intriguing observation that although wildfire smoke exposure primarily induces modest pulmonary inflammation, it leads to significant neuroinflammatory sequelae. These include microglial activation, peripheral immune infiltration, and altered neuroprotective metabolites. To shed light on the timing of resolution of this neuroinflammation, a novel approach involved replicating biomass smoke inhalation exposure in a controlled laboratory setting.
Methodology: Investigating Inflammatory Resolution
Utilizing a serial euthanasia study design, researchers aimed to dissect the temporal dynamics of the inflammatory endothelial response and its resolution. This investigation relied on advanced techniques such as flow cytometry and metabolomics approaches. These methodologies facilitated the precise characterization of endothelial cell phenotypes and the detection of neuroinflammatory markers.
Conclusion
In conclusion, the escalation of acres burned by wildfires has led to a surge in wildfire smoke exposure, impacting air quality nationwide. The resulting neuroinflammation, now linked to neurological outcomes, is a multi-faceted phenomenon intricately intertwined with pulmonary proteolysis, blood-brain barrier disruption, and immune cell transmigration.
By replicating these exposures in a controlled laboratory setting and employing cutting-edge techniques, researchers are unraveling the timeline of inflammatory resolution, contributing to a deeper understanding of the complex interplay between pollutants, the lungs, and the central nervous system. This knowledge is essential for developing strategies to mitigate the neurological consequences of wildfire smoke exposure and to safeguard public health.
reference link: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02874-y#Sec16
