Propylene Glycol after TBI: Biomarker of Altered Brain Metabolism

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DESCRIPTION (provided by applicant): We have recently demonstrated that propylene glycol (PG) concentrations in cerebrospinal fluid (a clear fluid that surrounds the brain) increase following human traumatic brain injury to above what would normally be expected given its use in delivering drugs in the intensive care unit (ICU). This finding led us to think that PG is produced within the brain via the methylglyoxal pathway, an alternate glucose (brain fuel) energy production pathway. It has been well established that blood glucose are elevated following brain injury (Vespa et al., 2006; Classen et al., 2005; Vespa et al., 2002). However, to our knowledge few, if any, studies have addressed the presence of PG in the brain following trauma. As a result, it is crucial to the development of a `metabolic therapy' for brain trauma to investigate these pathways. Given the lack of the currently available literature on brain injury energy production to completely explain the mechanisms behind these metabolic changes, we believe it is of utmost importance to investigate the extent of alternate glucose energy production pathways and PG production. Due to its high abundance following injury and its potential potency in interrupting energy production in the brain, PG might significantly alter the currently prevailing post-injury energy production paradigm. Especially since PG might be the key to answer the question of why the brain does not produce energy after injury despite fuel availability. Consequently, we intend to confirm that propylene glycol is in fact produced as a byproduct of the methylglyoxal pathway by establishing a correlation between these compounds. These studies will guide future attempts to find the exact pathway involved in the formation of PG as well as all other compounds involved in this pathway by using C13 tracer studies. Additionally, we plan to construct a timeline of PG levels in the human brain over the first week post-injury to guide future efforts intended to counteract its production and breakdown. PUBLIC HEALTH RELEVANCE: Only few, if any, studies have addressed the presence of propylene glycol in the brain following trauma. As a result, it is crucial to the development of a `metabolic therapy' for brain trauma to investigate these pathways. Particularly, because the presence of PG has been shown to be the stable end-product of a deleterious alternative glucose pathway. The concept of `metabolic therapy is of tremendous relevance to public health, since there is no cure for brain injury, a major cause of mortality and morbidity in the United States.