Browsing by Author "Maze, Mervyn"

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    Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.
    (PloS one, 2012-01) Yang, Ting; Zhuang, Lei; Rei Fidalgo, António M; Petrides, Evgenia; Terrando, Niccolo; Wu, Xinmin; Sanders, Robert D; Robertson, Nicola J; Johnson, Mark R; Maze, Mervyn; Ma, Daqing
    It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon), in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic) neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be tested in clinical trials in the future.
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    Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.
    (Anesthesiology, 2012-12) Sheng, Siyuan P; Lei, Beilei; James, Michael L; Lascola, Christopher D; Venkatraman, Talaignair N; Jung, Jin Yong; Maze, Mervyn; Franks, Nicholas P; Pearlstein, Robert D; Sheng, Huaxin; Warner, David S

    Background

    Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval.

    Methods

    Rats were subjected to 70 min temporary focal ischemia. Ninety minutes later, rats were treated with 0, 15, 30, or 45% Xe for 20 h or 0 or 30% Xe for 8, 20, or 44 h. Outcome was measured after 7 days. In another experiment, after ischemia, rats were maintained at 37.5° or 36.0°C for 20 h with or without 30% Xe. Outcome was assessed 28 days later. Finally, mice were subjected to intracerebral hemorrhage with or without 30% Xe for 20 h. Brain water content, hematoma volume, rotarod function, and microglial activation were measured.

    Results

    Cerebral infarct sizes (mean±SD) for 0, 15, 30, and 45% Xe were 212±27, 176±55, 160±32, and 198±54 mm, respectively (P=0.023). Neurologic scores (median±interquartile range) followed a similar pattern (P=0.002). Infarct size did not vary with treatment duration, but neurologic score improved (P=0.002) at all xenon exposure durations (8, 20, and 44 h). Postischemic treatment with either 30% Xe or subtherapeutic hypothermia (36°C) had no effect on 28-day outcome. Combination of these interventions provided long-term benefit. Xenon improved intracerebral hemorrhage outcome measures.

    Conclusion

    Xenon improved focal ischemic outcome at 7, but not 28 days postischemia. Xenon combined with subtherapeutic hypothermia produced sustained recovery benefit. Xenon improved intracerebral hemorrhage outcome. Xenon may have potential for clinical stroke therapy under carefully defined conditions.