Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia.
OBJECTIVE
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.
Dingley
John
J
University of Wales Swansea, United Kingdom.
Tooley
James
J
Porter
Helen
H
Thoresen
Marianne
M
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010865:Pilot Projects; D011897:Random Allocation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors; D014978:Xenon / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon; D016202:N-Methylaspartate