Carbon monoxide and the brain growth spurt
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The studies proposed in this grant are designed to examine the influence of exposure to carbon monoxide (CO) at a critical period of growth in the brain. This period is the brain growth spurt which coincides with the start of myelin (white matter) formation. During this crucial stage the brain undergoes cell division and the development of an intricate multi-cellular organization, particularly that of the myelin-forming cells. The growth of these cells require the production of lipids (fats). At this time, metabolic activity and energy needs are dynamic. It is believed that anything that would cause a delay in these growth events would cause damage to the brain. Prior research has clearly demonstrated that pregnant women exposed to tobacco smoke, either directly or second-hand, give birth to children with lower birth weights. However, in these previous studies it was not possible to analyze for deficiencies in brain size or function. This deficit in general fetal growth takes place during the critical time for brain development. For the human infant this critical time spans the third trimester of pregnancy into the first 6 months after birth. Our hypothesis states that these growth deficiencies are a result of exposure to CO from tobacco smoke. To examine the effect directly on brain, we plan to use the artificially-reared rat pup which is our animal model. In the rat pup, unlike the human baby, the important stage for the brain growth spurt and onset of myelin formation takes place after birth when the pups are fed milk. The artificially-reared rat pups are fed rat milk substitutes under carefully controlled conditions. To test our hypothesis these rat pups will be exposed to CO in amounts found in tobacco smoke to find out if the brain is compromised at this vulnerable age. Tobacco smoke contains more than 3000 active compounds and it is known that the two most common are nicotine and CO. One cigarette can yield from 0.003 to 0.05 gram CO and one cigar up to 0.8 gram CO. Nonsmokers can be exposed to significant amounts of CO because it has been shown the air can contain up to 4000 parts per million CO from tobacco smoke. Carbon monoxide is a general poison. CO inhaled with air decreases the oxygen carrying capacity of red blood cells and this can reduce the availability of oxygen to organs. In addition, CO is known to block the energy production centers within cells. Our research project seeks to address how CO influences brain growth and function from several perspectives; (1) by examining cognitive function through standard behavioral tests in a collaboration with Dr David Hovda, a Clinical Psychologist at UCLA; (2) by monitoring the cellular infrastructure of the brain; and (3) by examining the lipid composition, and capacity of developing brain to produce its major lipids. Preliminary data from our milk fed rat pup model shows that exposure to tobacco smoke causes a statistically significant reduction in brain weight with a modest, but insignificant reduction in body weight. This means that tobacco smoke and thus CO may influence developmental milestones in brain which may never be recouped at later stages in development. The two key considerations are that lipid production requires energy and that the brain is independent and produces greater than 90% of the major lipids it needs, since most lipids cannot be imported from the blood. This research is expected to advance our understanding of the seriousness of second hand cigarette smoke on early brain development.