Asynchronous administration of xenon and hypothermia significantly reduces brain infarction in the neonatal rat.

Abstract

Neonatal asphyxia causes long-term neurological and behavioural impairment in the developing brain. Concurrent administration of xenon and hypothermia synergistically reduces long-term damage in a rat model of neonatal asphyxia. This study sought to investigate whether asynchronous administration of xenon and hypothermia is capable of combining synergistically to provide neuroprotection. Seven-day-old rats were subjected to right common carotid artery occlusion followed by 90 min hypoxia with 8% oxygen. After a 1 h recovery period, rats received asynchronous administration of mild hypothermia (35 degrees C) and xenon (20%) with a 1 or 5 h gap between interventions, xenon (20%) alone, or mild hypothermia (35 degrees C) alone. Infarct volume in the brain was measured 4 days after injury. Administration of hypothermia or xenon alone, 1 and 6 h after the hypoxic ischaemic insult, respectively, provided no neuroprotection. Asynchronous administration of xenon and hypothermia at a 1 h interval produced a significant reduction in infarct volume [93 (7) vs 74 (8); P < 0.05]. Reduction in infarct volume was also present when hypothermia and xenon were asynchronously administered with an intervening gap of 5 h [97 (5) vs 83 (3); P < 0.05]. This finding provides a rationale for investigating the combined use of hypothermia and xenon in a progressive manner for the management of neonatal asphyxia. Thus, hypothermia can be administrated at the site of delivery and xenon can be administered later.