The Marianne Thoresen Research Group

Experimental research and clinical work in brain protection of the newborn

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Worldwide, newborn infants suffer death or permanent brain damage caused by diseases arising before or around the time of birth. Our research groups (in Oslo, Norway and Bristol, UK) do translational research aimed at developing effective treatments against hypoxic-ischemic injury in the newborn, including prediction of severity and long term outcomes.

The neuroprotective effect of cooling (therapeutic hypothermia) was first verified in experimental models and led to clinical trials where we and others documented the same neuroprotective effect in humans. We are currently undertaking a randomised clinical trial of whether breathing the inert gas xenon during cooling improves outcomes in newborn asphyxiated infants. In experimental models explored prior to this clinical trial, xenon combined with hypothermia doubled neuroprotection as compared to hypothermia alone. Clinically, we follow up cooled infants long term at age 6-8. In the laboratory we undertake further work on xenon neuroprotection, other cooling protocols and the interaction of cooling with infection and hyperoxia, EEG, cerebral blood flow and the cardiovascular system.

By integrating studies of normal physiological changes in organ systems with pathological changes seen after hypoxic-ischemic injury, we have developed experimental models that mimic either global injury or brain haemorrhage leading to permanent disability in children.

Walløe L, Hjort L N, Thoresen M. Major consern about late hypothermia study. Neonatal Neuroscience, School of Clinical Sciences, St.Michael’s Hospital,University of Bristol, Bristol, United Kingdom. doi: 10.1111/apa.14640

Thoresen M. Combining two good treatments makes it worse. [Commentary on ‘Interaction between hypothermia and delayed mesenchymal stem cell therapy in neonatal hypoxic-ischemic brain injury’. Felderhoff-Muser et al, doi: 10.1016/j.bbi.2018.02.006]. Commentary published in Brain Behavior and Immunity 2018 Apr 17. pii: S0889-1591(18)30125-9. doi: 10.1016/j.bbi.2018.04.008

Sabir M, Dingley J, Scull-Brown E, Chakkarapani E, Thoresen M. Fentanyl induces cerebellar internal granular cell layer apoptosis in healthy newborn pigs. Frontiers in Neurology, section Pediatric Neurology. In press, April 2018. doi.org/10.3389/fneur.2018.00294

Falck M, Osredkar D, Wood T R, Maes E, Flatebø T, Sabir H, Thoresen M. Neonatal Systemic Inflammation Induces Inflammatory Reactions and Brain Apoptosis in a Pathogen-Specific Manner. Neonatology 23 des 2017. doi:10.1159/000481980. .

Liu X, Jary S, Cowan F, Thoresen M. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia 1-10,2017 doi: 10.1111/epi.13914online Liu X et al 2017 Epilepsia14586865.

Skranes J H, Løhaugen G, Schumacher E M, Osredkar D, Server A, Cowan F M, Stiris T, Fugelseth D, Thoresen M. Amplitude-Integrated Electroencephalography Improves the Identification of Infants with Encephalopathy for Therapeutic Hypothermia and Predicts Neurodevelopmental Outcomes at 2 Years of Age. The Journal of Pediatrics 2017. doi: 10.1016/j.poeds.2017.04.041.

Wood T, Hobbs C, Falck M, Brun A C, Løberg E M, Thoresen M.Rectal temperature in the first five hours after hypoxia-ischaemia critically affects neuropathological outcomes in neonatal rats. Pediatric Research 2017. doi: 10.1038/pr.2017.51pr201751.

Falck M, Osredkar D, Maes E, Flatebo T, Wood T, Sabir H, Thoresen M. Hypothermic Neuronal Rescue from Infection-sensitised Hypoxic-Ischaemic Brain Injury is Pathogen Dependent.doi:10.1159/000455838 In Press 2017– J Developmental Neuroscience.

Elstad M, Liu X, Thoresen M. Heart rate response to therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy. Resuscitation Jun 28;106:53-57. doi: 10.1016/j.resuscitation.2016.06.023.

Wood T, Smit E, Maes E, Osredkar D, Falck M, Elstad M, Thoresen M - Monitoring of cerebral blood flow during hypoxia-ischemia and resuscitation in the neonatal rat using laser speckle imaging. Physiological reports DOI: 10.14814/phy2.12749

Wood T, Osredkar D, Puchades M, Maes E, Falck M, Flatebø T, Walloe L, Sabir H, Thoresen M - Treatment temperature and insult severity influence neuroprotective effects of Therapeutic Hypothermia. Scientifc Reports DOI: 10.1038/srep23430

Sabir H, Wood T, Gill H, Liu X, Dingley J, Thoresen M - Xenon depresses aEEG background voltage activity whilst maintaining cardiovascular stability in sedated healthy newborn pigs. Journal of the Neurological Science 2016; doi: 10.1016/j.jns.2016.02.051