Upregulation of cholesterol 24-hydroxylase following hypoxia-ischemia in neonatal mouse brain.

BackgroundMaintenance of cholesterol homeostasis is crucial for brain development. Brain cholesterol relies on de novo synthesis and is cleared primarily by conversion to 24S-hydroxycholesterol (24S-HC) with brain-specific cholesterol 24-hydroxylase (CYP46A1). We aimed to investigate the impact of hypoxia-ischemia (HI) on brain cholesterol metabolism in the neonatal mice.MethodsPostnatal day 9 C57BL/6 pups were subjected to HI using the Vannucci model. CYP46A1 expression was assessed with western blotting and its cellular localization was determined using immunofluorescence staining. The amount of brain cholesterol, 24S-HC in the cortex and in the serum, was measured with enzyme-linked immunosorbent assay (ELISA).ResultsThere was a transient cholesterol loss at 6 h after HI. CYP46A1 was significantly upregulated at 6 and 24 h following HI with a concomitant increase of 24S-HC in the ipsilateral cortex and in the serum. The serum levels of 24S-HC correlated with those in the brain, as well as with necrotic and apoptotic cell death evaluated by the expression of spectrin breakdown products and cleaved caspase-3 at 6 and 24 h after HI.ConclusionEnhanced cholesterol turnover by activation of CYP46A1 represents disrupted brain cholesterol homeostasis early after neonatal HI. 24S-HC might be a novel blood biomarker for severity of hypoxic-ischemic encephalopathy with potential clinical application.

Increasing Health Risks During Outdoor Sports Due To Climate Change in Texas: Projections Versus Attitudes.

Extreme heat is a recognized threat to human health. This study examines projected future trends of multiple measures of extreme heat across Texas throughout the next century, and evaluates the expected climate changes alongside Texas athletic staff (coach and athletic trainer) attitudes toward heat and climate change. Numerical climate simulations from the recently published Community Earth System Model version 2 and the Climate Model Intercomparison Project were used to predict changes in summer temperatures, heat indices, and wet bulb temperatures across Texas and also within specific metropolitan areas. A survey examining attitudes toward the effects of climate change on athletic programs and student athlete health was also distributed to high-school and university athletic staff. Heat indices are projected to increase beyond what is considered healthy/safe limits for outdoor sports activity by the mid-to-late 21st century. Survey results reveal a general understanding and acceptance of climate change and a need for adjustments in accordance with more dangerous heat-related events. However, a portion of athletic staff still do not acknowledge the changing climate and its implications for student athlete health and their athletic programs. Enhancing climate change and health communication across the state may initiate important changes to athletic programs (e.g., timing, duration, intensity, and location of practices), which should be made in accordance with increasingly dangerous temperatures and weather conditions. This work employs a novel interdisciplinary approach to evaluate future heat projections alongside attitudes from athletic communities toward climate change.