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Xenon and Sevoflurane Provide Analgesia during Labor and Fetal Brain Protection in a Perinatal Rat Model of Hypoxia-Ischemia

Yang, T; Zhuang, L; Fidalgo, AMR; Petrides, E; Terrando, N; Wu, X; Sanders, RD; ... Ma, D; + view all (2012) Xenon and Sevoflurane Provide Analgesia during Labor and Fetal Brain Protection in a Perinatal Rat Model of Hypoxia-Ischemia. PLOS ONE , 7 (5) , Article e37020. 10.1371/journal.pone.0037020. Green open access

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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.

Type: Article
Title: Xenon and Sevoflurane Provide Analgesia during Labor and Fetal Brain Protection in a Perinatal Rat Model of Hypoxia-Ischemia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0037020
Publisher version: http://dx.doi.org/10.1371/journal.pone.0037020
Language: English
Additional information: © 2012 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by a grant (SP4385) from Action Medical Research, West Sussex, UK, to Dr. Ma. Drs. Yang and Zhuang were supported by the fellowship from the Chinese Society of Anesthesiology, Beijing, China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology
URI: https://discovery.ucl.ac.uk/id/eprint/1376307
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