New research suggests that even short-term exposure to wood smoke can lead to persistent neuroinflammatory responses, changes in immune cell activity, and alterations in brain metabolites. These effects could contribute to cognitive deficits, attention problems, and mood alterations. The findings have been published in the Journal of Neuroinflammation.
Wood smoke, a common component of air pollution in regions affected by wildfires, has long been associated with adverse health effects in humans. From respiratory issues to cognitive impairments, the impact of wood smoke on human well-being is a growing concern, especially in light of increasing wildfire activity worldwide.
To gain deeper insights into the effects of wood smoke on the brain, a group of researchers conducted a comprehensive study using mice as a model organism. This study aimed to uncover the neurological consequences of wood smoke exposure and shed light on potential mechanisms underlying these effects.
“We have known that blood vessels throughout the body are a key indirect target of inhaled pollutants. The blood brain barrier is a unique vascular bed, and we theorized that such exposures may lead to inflammation in the brain due to neurovascular effects,” explained study author Matthew Campen, a Regents’ Professor at the University of New Mexico and co-director of the UNM Clinical & Translational Science Center.
To conduct their research, the scientists used an 8-week-old female mouse model. These mice were exposed to wood smoke every other day for a period of 2 weeks, simulating a real-world wildfire smoke exposure scenario. The average concentration of wood smoke during the exposure was measured at 0.5 mg/m3, aligning with real-world exposure levels.
The researchers then conducted a series of experiments to investigate the impact of wood smoke on different aspects of health and biology. They analyzed cerebrovascular endothelial cells, immune cell infiltration in the brain, and metabolomic changes in the hippocampal region.
The researchers found significant changes in cerebrovascular endothelial cells, which are crucial for brain health. Specifically, there was an increase in CD31Hi endothelial cells, which are associated with an anti-inflammatory response. This increase persisted for up to 14 days post-exposure. In contrast, the population of CD31Med endothelial cells, linked to a pro-inflammatory response, decreased until day 14 but then returned to normal levels. These changes correlated with the expression of various markers related to inflammation.
This indicates “that the endothelial cells – the cells that line the blood vessels – are actively trying to help resolve the problem,” Campen explained. “Initially, they help drive the neuroinflammation, but they quickly transition to an anti-inflammatory behavior.
Wood smoke exposure triggered the activation of microglia, a type of immune cell in the brain. This activation began on day 7 and persisted until day 28. Additionally, peripheral immune cells started infiltrating the brain, with significant increases observed on day 14.
Neutrophils, another type of immune cell, displayed a complex response pattern, with a reduction in their population on day 1, an increase on day 14, and a subsequent reduction on day 28. However, the remaining neutrophils on day 28 appeared to be highly inflammatory.
Metabolomic analysis of the hippocampal region revealed significant changes in various small molecules. Notably, there were reductions in metabolites related to cognition and mood, including glutamate, glutaurine, 3-MT, and 5α-DHP. These findings suggest that wood smoke exposure may impact cognitive function and mood. Additionally, changes in metabolites associated with the NAD+ synthesis pathway were observed, which is involved in cellular energy production and repair.
The findings provide evidence that the “neurological effects of exposure to wood smoke, such as from wildfires, may last weeks after the exposure,” Campen told PsyPost. “We are still uncertain as to the breadth of effects, but neuroinflammation can underlie mood disorders, including anxiety and depression, and also impact learning and memory. More worrisome is the potential to impact long-term neurodegenerative diseases like dementia, but a lot of work needs to be done to understand the links between these exposures and neurological diseases.”
However, it’s important to acknowledge the limitations of this study. The research was conducted in mice, and while these findings provide valuable insights, translating them directly to human health requires caution. Mice may not perfectly replicate the complexity of human responses to wood smoke.
“This is a tip-of-the-iceberg study and we need to better understand how these neuroinflammatory effects promote neurological outcomes, and also we have to appreciate that mice likely have responses that can differ from humans,” Campen said. “Notably, the wood smoke exposure conditions were very realistic and similar to that experienced by millions of people in the USA every summer from wildfires.”
The study, “Biomass smoke inhalation promotes neuroinflammatory and metabolomic temporal changes in the hippocampus of female mice“, was authored by David Scieszka, Yan Jin, Shahani Noor, Ed Barr, Marcus Garcia, Jessica Begay, Guy Herbert, Russell P. Hunter, Kiran Bhaskar, Rahul Kumar, Rama Gullapalli, Alicia Bolt, Mark A. McCormick, Barry Bleske, Haiwei Gu, and Matthew J. Campen.
