It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women use
some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used
as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents
with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon), in
reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective
effects at subanesthetic levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of intrauterine perinatal
asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation
using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult
day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the
number of viable neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a surrogate mother for 50
days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected
by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord.
Both agents also reduced the number of caspase-3 positive (apoptotic) neurons and increased cell viability in the
hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely
after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia
and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with
neuroprotective properties may be effective in preventing HIE and should be tested in clinical trials in the future.