Eucalyptus Wood Smoke Extract Elicits a Dose-Dependent Effect in Brain Endothelial Cells

Area of Science:

• Environmental Health
• Neuroscience
• Toxicology

Background:

• Increasing wildfire frequency and smoke exposure are linked to cognitive and neurological deficits.
• The precise mechanisms by which wildfire smoke affects the blood-brain barrier remain largely unknown.
• Understanding cellular and molecular brain changes from smoke exposure is crucial for public health.

Purpose of the Study:

• To investigate the acute effects of eucalyptus wood smoke extract (WSE) on brain endothelial cells in vitro.
• To assess potential neurotoxicity induced by wildfire smoke components.
• To compare the response of primary and immortalized human brain endothelial cells to WSE.

Main Methods:

• Primary human brain microvascular endothelial cells (HBMEC) and hCMEC/D3 cells were exposed to varying doses of WSE for 24 hours.
• Interleukin-8 (IL-8) levels were measured.
• RNA sequencing (RNA-seq) was performed to analyze gene expression changes, focusing on pathways like aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (NRF2), and tight junction markers.

Main Results:

• WSE exposure led to a dose-dependent increase in IL-8 production in both cell types.
• RNA-seq revealed a dose-dependent upregulation of AhR and NRF2 pathway genes.
• WSE treatment decreased tight junction markers in both HBMEC and hCMEC/D3 cells, with HBMEC showing higher baseline expression of these markers.

Conclusions:

• Acute exposure to eucalyptus WSE alters brain endothelial cell function by increasing IL-8 and reducing tight junction integrity.
• These changes may be mediated by the AhR and NRF2 signaling pathways.
• Primary HBMEC represent a more suitable in vitro model for studying the neurotoxic effects of wood smoke on the brain endothelial barrier compared to hCMEC/D3 cells.