Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Feb 2017
Comparative StudyComparability of [18F]THK5317 and [11C]PIB blood flow proxy images with [18F]FDG positron emission tomography in Alzheimer's disease.
For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to reference region (R1) has been shown to serve as a marker of brain perfusion, and, due to the strong coupling between perfusion and metabolism, as a proxy for glucose metabolism. In the present study, 11 prodromal Alzheimer's disease and nine Alzheimer's disease dementia patients underwent [18F]THK5317, carbon-11 Pittsburgh Compound-B ([11C]PIB), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography to assess the possible use of early-phase [18F]THK5317 and R1 as proxies for brain perfusion, and thus, for glucose metabolism. Discriminative performance (prodromal vs Alzheimer's disease dementia) of [18F]THK5317 (early-phase SUVr and R1) was compared with that of [11C]PIB (early-phase SUVr and R1) and [18F]FDG. ⋯ Differences in correlations between early-phase and R1 ([18F]THK5317 and [11C]PIB) and [18F]FDG, were not statistically significant, nor were differences in area under the curve values in the discriminative analysis. Our findings suggest that early-phase [18F]THK5317 and R1 provide information on brain perfusion, closely related to glucose metabolism. As such, a single positron emission tomography study with [18F]THK5317 may provide information about both tau pathology and brain perfusion in Alzheimer's disease, with potential clinical applications.
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J. Cereb. Blood Flow Metab. · Feb 2017
Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage.
We previously demonstrated that stimulation of astrocyte mitochondrial ATP production via P2Y1 receptor agonists was neuroprotective after cerebral ischemic stroke. Another mechanism that increases ATP production is fatty acid oxidation (FAO). We show that in primary human astrocytes, FAO and ATP production are stimulated by 3,3,5 triiodo-l-thyronine (T3). ⋯ In vivo, 95% of HADHA co-localize with glial-fibrillary acidic protein, suggesting the effect of HADHA is astrocyte mediated. These results suggest that astrocyte-FAO modulates lesion size and is required for T3-mediated neuroprotection post-stroke. To our knowledge, this is the first report of a neuroprotective role for FAO in the brain.