Ma Daqing, Hossain Mahmuda, Chow Andre, Arshad Mubarik, Battson Renee M, Sanders Robert D, Mehmet Huseyin, Edwards A David, Franks Nicholas P, Maze Mervyn
Department of Anaesthetics and Intensive Care, Faculty of Medicine, Imperial College London, London, United Kingdom.
Ann Neurol. 2005 Aug;58(2):182-93. doi: 10.1002/ana.20547.
Perinatal asphyxia can result in neuronal injury with long-term neurological and behavioral consequences. Although hypothermia may provide some modest benefit, the intervention itself can produce adverse consequences. We have investigated whether xenon, an antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor, can enhance the neuroprotection provided by mild hypothermia. Cultured neurons injured by oxygen-glucose deprivation were protected by combinations of interventions of xenon and hypothermia that, when administered alone, were not efficacious. A combination of xenon and hypothermia administered 4 hours after hypoxic-ischemic injury in neonatal rats provided synergistic neuroprotection assessed by morphological criteria, by hemispheric weight, and by functional neurological studies up to 30 days after the injury. The protective mechanism of the combination, in both in vitro and in vivo models, involved an antiapoptotic action. If applied to humans, these data suggest that low (subanesthetic) concentrations of xenon in combination with mild hypothermia may provide a safe and effective therapy for perinatal asphyxia.
围产期窒息可导致神经元损伤，并产生长期的神经和行为后果。尽管低温可能有一定益处，但该干预本身也会产生不良后果。我们研究了谷氨酸受体N-甲基-D-天冬氨酸亚型的拮抗剂氙气是否能增强轻度低温提供的神经保护作用。单独使用时无效的氙气和低温干预联合应用，可保护因氧糖剥夺而受损的培养神经元。新生大鼠缺氧缺血性损伤4小时后给予氙气和低温联合治疗，通过形态学标准、半球重量以及损伤后30天内的功能性神经学研究评估，其提供了协同神经保护作用。在体外和体内模型中，联合治疗的保护机制均涉及抗凋亡作用。如果应用于人类，这些数据表明低（亚麻醉）浓度的氙气与轻度低温联合应用，可能为围产期窒息提供一种安全有效的治疗方法。
