{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:23:25Z","timestamp":1791332605427,"version":"4.3.1"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,6,14]],"date-time":"2011-06-14T00:00:00Z","timestamp":1308009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective:<\/jats:title><jats:p>Additional treatments for therapeutic hypothermia are required to maximize neuroprotection for perinatal asphyxial encephalopathy. We assessed neuroprotective effects of combining inhaled xenon with therapeutic hypothermia after transient cerebral hypoxia\u2013ischemia in a piglet model of perinatal asphyxia using magnetic resonance spectroscopy (MRS) biomarkers supported by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Thirty\u2010six newborn piglets were randomized (all groups n = 9), with intervention from 2 to 26 hours, to: (1) normothermia; (2) normothermia + 24 hours 50% inhaled xenon; (3) 24 hours hypothermia (33.5\u00b0C); or (4) 24 hours hypothermia (33.5\u00b0C) + 24 hours 50% inhaled xenon. Serial MRS was acquired before, during, and up to 48 hours after hypoxia\u2013ischemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Mean arterial blood pressure was lower in all treatment groups compared with normothermia (<jats:italic>p<\/jats:italic> &lt; 0.01) (although &gt;40mmHg); the combined therapy group required more fluid boluses (<jats:italic>p<\/jats:italic> &lt; 0.05) and inotropes (<jats:italic>p<\/jats:italic> &lt; 0.001). Compared with no intervention, both hypothermia and xenon\u2010augmented hypothermia reduced the temporal regression slope magnitudes for phosphorus\u2010MRS inorganic phosphate\/exchangeable phosphate pool (EPP) and phosphocreatine\/EPP (both <jats:italic>p<\/jats:italic> &lt; 0.05); for lactate\/<jats:italic>N<\/jats:italic>\u2010acetylaspartate (NAA), only xenon\u2010augmented hypothermia reduced the slope (<jats:italic>p<\/jats:italic> &lt; 0.01). Xenon\u2010augmented hypothermia also reduced transferase\u2010mediated deoxyuridine triphosphate nick\u2010end labeling (TUNEL)<jats:sup>+<\/jats:sup> nuclei and caspase 3 immunoreactive cells in parasagittal cortex and putamen and increased microglial ramification in midtemporal cortex compared with the no treatment group (<jats:italic>p<\/jats:italic> &lt; 0.05). Compared with hypothermia, however, combination treatment did not reach statistical significance for any measure. Lactate\/NAA showed a strong positive correlation with TUNEL; nucleotide triphosphate\/EPP showed a strong negative correlation with microglial ramification (both <jats:italic>p<\/jats:italic> &lt; 0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation:<\/jats:title><jats:p>Compared with no treatment, xenon\u2010augmented hypothermia reduced cerebral MRS abnormalities and cell death markers in some brain regions. Compared with hypothermia, xenon\u2010augmented hypothermia did not reach statistical significance for any measure. The safety and possible improved efficacy support phase II trials. 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