title: Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.
abstract: 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.
authors.affiliation: Anesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhuang
authors.forename: António M
authors.initials: AM
authors.lastname: Rei Fidalgo
authors.forename: Evgenia
authors.initials: E
authors.lastname: Petrides
authors.forename: Niccolo
authors.initials: N
authors.lastname: Terrando
authors.forename: Xinmin
authors.initials: X
authors.lastname: Wu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sanders
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Robertson
authors.forename: Mark R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D000698:Analgesia / Q000379:methods; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015331:Cohort Studies; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000517:prevention & control*; D048949:Labor Pain / Q000188:drug therapy* / Q000378:metabolism; D008569:Memory Disorders / Q000378:metabolism / Q000517:prevention & control; D008738:Methyl Ethers / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D014978:Xenon / Q000494:pharmacology*
chemical_list: D008738:Methyl Ethers; D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D000077149:Sevoflurane; D014978:Xenon; D053148:Caspase 3