CNS neuroscience & therapeutics
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Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross-sectional and longitudinal rate of brain atrophy, quantitatively measured by fully-automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene-positive subjects with presymptomatic to advanced HD, and age-matched healthy controls. ⋯ Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG-based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R(2)= 0.25, P < 0.0001).
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Propofol (2,6-diisopropylphenol) is a versatile, short-acting, intravenous (i.v.) sedative-hypnotic agent initially marketed as an anesthetic, and now also widely used for the sedation of patients in the intensive care unit (ICU). At the room temperature propofol is an oil and is insoluble in water. It has a remarkable safety profile. ⋯ EDTA is also a chelator of divalent ions such as calcium, magnesium, and zinc. Recently, EDTA has been reported to exert a neuroprotective effect itself by chelating surplus intracerebral zinc in an ischemia model. This article reviews the neuroprotective effects of propofol and its mechanism of action.