Saturday, November 23, 2024
11/23/2024
PROJECT SUMMARY/ ABSTRACT Obstructive sleep apnea (OSA), a life-threatening condition, affects ~10% adults in the United States. The condition is accompanied by multiple symptoms (autonomic, breathing, mood, and cognition), which are linked to increased morbidity and mortality and decreased quality of life. The impaired functions likely result from brain changes in sites that mediate these regulations, but the pathological mechanisms contributing to brain changes are unclear. Intermittent hypoxia (IH), a primary characteristic of OSA, induces oxidative stress, leading to excessive production of reactive oxygen species (ROS) that encourages neuroinflammation and activates immune and glial cells; that sequence leads to regional increases in brain temperature, contributing to tissue damage. Moreover, IH induces mitochondrial dysfunction, altering metabolites, including the N-acetyl- aspartate (NAA; neuronal integrity), choline (Cho; membrane metabolism/integrity/turnover), creatine (Cr; energy metabolism), myo-inositol (MI; astrocyte proliferation/osmotic balance), and lactate (Lac; anaerobic metabolism). Also, antioxidants, including glutathione (GSH) that plays a significant role against oxidative stress, regulate neuronal/cellular protection from excessive ROS. However, the distribution of regional brain temperatures, metabolites, and antioxidant status in OSA is unknown, leaving a gap in knowledge of sources of injury that can be examined non-invasively with the 3D Echo Planar Spectroscopic Imaging (3D EPSI) and the MEshcher–GArwood Point RESolved Spectroscopy (MEGA-PRESS). Therefore, using 100 moderate-to- severe OSA and 100 age- and sex-matched controls, the specific aims are to: 1) examine regional brain temperatures, using 3D EPSI, in OSA and controls; 2) assess whole-brain metabolites (NAA, Cho, Cr, MI, and Lac), using 3D EPSI, antioxidant (GSH) levels from the posterior and anterior cingulate and anterior insula, using MEGA-PRESS, in OSA and controls; 3) determine the relationships between brain temperatures and Lac and MI levels with disease severity in OSA adults; and 4) assess regional brain temperature and metabolites changes, using 3D EPSI, after 6-months in OSA with and without continuous positive airway pressure (CPAP) compliance. In summary, the objective is to examine IH-induced oxidative stress and mitochondrial dysfunction processes contributing to brain changes in OSA, reflected as changes in regional brain temperatures and metabolites, and antioxidant in multiple brain sites, links between brain temperature, metabolites, and disease severity, and assess if the CPAP normalizes such changes in OSA. The findings have important implications for identifying interventions (nonsteroidal anti-inflammatory drugs, antioxidant, and Cr therapies as used in other conditions) to fully rescue brain changes in OSA with and without CPAP in those sites, which will benefit to dysfunctions, especially in non-CPAP compliant OSA or no treatment, and could dramatically improve the morbidity, mortality, and life quality.
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