Approximately 1 in 10,000 North Americans have an aneurysmal subarachnoid hemorrhage (aSAH) each year. It is a devastating disease with a combined morbidity and mortality greater than 50%. Subarachnoid hemorrhage (SAH) can lead to neuronal injury and can impair cognitive function by increasing pressure on the brain. For these reasons, it is crucial that effective therapies for patients suffering from SAH are found. This thesis will discuss the clinical characteristics of SAH, as well as possible targets for therapeutic intervention. Carbon monoxide (CO) is commonly known as an environmental pollutant and toxic diatomic gas, infamous for its extremely high affinity for hemoglobin. Research has shown that CO possesses many of the same functions of nitric oxide. These functions include vasodilation, inhibition of platelet aggregation, and anti-proliferative effects on smooth muscle. It is also known as an anti-inflammatory agent under specific concentrations and conditions.
Heme oxygenase isozymes (HO-1 and HO-2) both generate CO in the brain following ischemic injury. In ischemic stroke, the function of CO is mediated by upregulation of Nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 plays a protective role in a variety of neurological and inflammatory disorders. Experiments have shown that exogenous CO administered to mice with middle cerebral artery occlusions results in smaller infarct sizes in the brain compared to mice without CO treatment. CO treatment was most effective in its protective role after a 1-hour delay in treatment versus a 3-hour delay. Thus, a therapeutic window of time in which CO treatment in ischemic stroke is most effective needs to be elucidated. The same is true for hemorrhagic stroke. The evidence suggests that CO could have a neuroprotective effect following subarachnoid hemorrhage by decreasing cerebral inflammation.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/31281 |
| Date | 24 July 2018 |
| Creators | Serva, Stephanie |
| Contributors | Offner, Gwynneth D., Garcia-Diaz, Fernando |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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