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Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
Swedish Univ Agr Sci, Dept Soil & Environm, Umea, Sweden.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
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2018 (English)In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 120, no 3, p. 546-554Article in journal (Refereed) Published
Abstract [en]

Background: Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Methods: Male mice were exposed to a single dose of ketamine (7.5 mg kg(-1) body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Results: Animals co-exposed to IR and ketamine displayed significant (P <= 0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P <= 0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P <= 0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Conclusion: Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2018. Vol. 120, no 3, p. 546-554
Keywords [en]
cognition, gamma rays, ketamine, mice, tau proteins
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-360552DOI: 10.1016/j.bja.2017.11.099ISI: 000438191300019PubMedID: 29452811OAI: oai:DiVA.org:uu-360552DiVA, id: diva2:1248461
Funder
Swedish Radiation Safety AuthorityAvailable from: 2018-09-14 Created: 2018-09-14 Last updated: 2018-09-14Bibliographically approved

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Buratovic, SonjaStenerlöw, BoFredriksson, AndersViberg, HenrikGordh, TorstenEriksson, Per

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British Journal of Anaesthesia
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