Most people are exposed to carbon monoxide (CO) every day through air pollution. Yet, while we understand the danger of CO poisoning, much less is known about health damage caused by persistent low-level CO poisoning. This is important, as research links CO air pollution at ’safe’ levels to diseases such as dementia and stroke.
Research shows that CO exposure at 3 parts per million, lower than UK guidelines, significantly impacts brain activation and brain blood flow (CBF). However, it is not yet known what low-level CO (like in air pollution) does to the human brain, especially long-term, nor if CO-related damage can be reversed/treated.
This project addresses this in humans using ultrasound of the brain (measures quick changes in CBF) and Magnetic Resonance Imaging (measures brain structure, neural activity and CBF distribution):
Study 1: What is the effect of low-level CO on the brain?
In healthy human volunteers, CBF and brain function will be measured at different, very low, levels of CO exposure. The project will image how the brain responds to memory/reaction tasks and how brain blood vessels respond to stimuli (called cerebrovascular reactivity). The research will also measure nitric oxide (NO) levels in the blood. NO is a molecule that regulates blood flow, and studies using high-level CO have shown that CO affects NO level. This could therefore be a way that CO causes disease.
Finally, researchers will measure oxidative stress in the brain, which is another way CO could cause disease. It will study non-smokers and smokers to see if earlier CO exposure (from cigarette smoke) affects responses. This will tell us the effect of low-level CO on brain function, and if this depends on how much CO a person has been exposed to in the past.
Study 2: What happens to the brain with Iong-term CO exposure
The study will take MRI data from the UK biobank project (www.ukbiobank.ac.uk,
containing >25,000 MRI data sets) and match this to atmospheric CO levels to see how subclinical damage to brain structure and function correlates with CO exposure. By doing this, the researchers will be able to tell how atmospheric CO is linked to brain structure/function. This will determine if and how long-term CO is bad for the brain.
Study 3: Can damage to the brain be reversed?
Researchers will ask smokers in Study 1 to change to e-cigarettes. E-cigarettes do not contain CO, and so they will see what happens when smokers that are chronically exposed to CO suddenly lower their CO levels. The project will measure changes in CBF, cerebrovascular reactivity, neural activity during memory/reaction tasks, NO level and oxidative stress level. This will test if any brain function impairment associated with long-term CO exposure can be reversed, and if it is linked to NO and/or oxidative stress becoming more normal. By doing this, we can begin investigating possible targets for treating or stopping CO-related damage.
Together, these studies will answer how low-level CO changes brain function and structure in humans, and if this can be reversed or even treated.
