Zhuang, Lei; Yang, T; Zhao, H; Fidalgo, ARei; Vizcaychipi, MP; Sanders, RD; Yu, B; Takata, M; Johnson, MR; Ma, D
Objective: Xenon provides neuroprotection in multiple
animal models; however, little is known about the other noble gases. The aim of the current study
was to compare xenon, argon, and helium neuroprotection in a neonatal asphyxia model in rats.
Design: Randomized controlled trial. Setting: Laboratory. Subjects: Seven-day-old postnatal
Sprague-Dawley rats. Interventions: Seventy percent argon, helium, xenon, or nitrogen balanced
with oxygen after hypoxic-ischemic brain injury. Measurements and Main Results: Control animals
undergoing moderate hypoxic-ischemia endured reduced neuronal survival at 7 days with impaired
neurologic function at the juvenile age compared with naive animals. Severe hypoxic-ischemic
damage produced a large cerebral infarction in controls. After moderate hypoxic-ischemia, all
three noble gases improved cell survival, brain structural integrity, and neurologic function on
postnatal day 40 compared with nitrogen. Interestingly, argon improved cell survival to naive
levels, whereas xenon and helium did not. When tested against more severe hypoxic-ischemic injury
only, argon and xenon reduced infarct volume. Furthermore, postinjury body weight in moderate
insult was lower in the helium-treated group compared with the naive, control, and other noble
gas treatment groups, whereas in the severe injurious setting, it is lower in both control and
helium-treated groups than other groups. In the nondirectly injured hemisphere, argon, helium,
and xenon increased the expression of Bcl-2, whereas helium and xenon increased Bcl-xL. In
addition, Bax expression was enhanced in the control and helium groups. Conclusions: These
studies indicate that argon and xenon provide neuroprotection against both moderate and severe
hypoxia-ischemic brain injury likely through prosurvival proteins synthesis. (Crit Care Med 2012;
40:1724-1730)