Published Online
on December 22, 2005

A more recent version of this article appeared on February 1, 2006

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Submitted on May 12, 2005
Revised on September 24, 2005
Accepted on September 28, 2005

Xenon Provides Short-Term Neuroprotection in Neonatal Rats When Administered After Hypoxia-Ischemia

John Dingley MB BCh, FRCA, MD; James Tooley MB, MRCP(UK), MRCPCH; Helen Porter MB ChB, BSc, FRCPath, MD; and Marianne Thoresen FRCPCH, MD, PhD^*

From the University of Wales Swansea (J.D.), United Kingdom; St Michael’s Hospital (J.T., M.T.), University of Bristol, United Kingdom; and Leicester Royal Infirmary (H.P.), United Kingdom.

^* To whom correspondence should be addressed. E-mail: marianne.thoresen{at}bristol.ac.uk.

Background and Purpose--Brain injury after hypoxic-ischemic insults evolves via an apoptotic/necrotic cascade. Glutamate over release and N-methyl-D-aspartate (NMDA) receptor over activation (excitotoxicity) are believed to trigger this process. Xenon is a nontoxic anesthetic gas that reduces neurotransmitter release and functionally antagonizes NMDA receptors. Administering xenon to hypoxic-ischemic newborns might be clinically effective if the neurotoxic processes continue evolving after delivery. We sought to determine whether xenon administration after the initial hypoxic-ischemic insult was neuroprotective.

Methods--Fifty 7-day-old rats received a 90-minute hypoxic insult after unilateral carotid ligation. They were then randomized to breathe 1 of 2 gas mixtures for 3 hours: 50% Xe/30% O₂/20% N₂ or 30% O₂/70% N₂.

Results--One week after hypoxic-ischemic survival, significant global protection was seen in the xenon group (80% less injury); cortex/white matter (88% versus 25%), hippocampus (62% versus 0%), basal ganglia (81% versus 25%), and thalamus (50% versus 0%; percentage of global damage score in nonxenon versus xenon groups, respectively).

Conclusions--Three hours of xenon administration commenced after hypoxia-ischemia in neonatal rats provides short-term neuroprotection. This finding suggests that treatment with xenon after perinatal asphyxia would also be neuroprotective. Because xenon does not cause other neurotoxic effects and has demonstrated minimal side effects in extensive anesthesia studies, it would make an ideal candidate for the treatment after human perinatal hypoxia-ischemia.

Key words: anesthesia • neuroprotection • xenon • hypoxia • ischemia • newborn • asphyxia • rats • N-methyl-D-aspartate

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