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Hyperglycemia Alters Expression of Cerebral Metabolic Genes after Cardiac Arrest
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.ORCID iD: 0000-0001-7913-4981
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2018 (English)In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 27, no 5, p. 1200-1211Article in journal (Refereed) Published
Abstract [en]

Background: Survivors of cardiac arrest often experience neurologic deficits. To date, treatment options are limited. Associated hyperglycemia is believed to further worsen the neurologic outcome. The aim with this study was to characterize expression pathways induced by hyperglycemia in conjunction with global brain ischemia.

Methods: Pigs were randomized to high or normal glucose levels, as regulated by glucose and insulin infusions with target levels of 8.5-10 mM and 4-5.5 mM, respectively. The animals were subjected to 5-minute cardiac arrest followed by 8 minutes of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Global expression profiling of the cortex using microarrays was performed in both groups.

Results: A total of 102 genes differed in expression at P<.001 between the hyperglycemic and the normoglycemic pigs. Several of the most strongly differentially regulated genes were involved in transport and metabolism of glucose. Functional clustering using bioinformatics tools revealed enrichment of multiple biological processes, including membrane processes, ion transport, and glycoproteins.

Conclusions: Hyperglycemia during cardiac arrest leads to differential early gene expression compared with normoglycemia. The functional relevance of these expressional changes cannot be deduced from the current study; however, the identified candidates have been linked to neuroprotective mechanisms and constitute interesting targets for further studies.

Place, publisher, year, edition, pages
2018. Vol. 27, no 5, p. 1200-1211
Keywords [en]
Cerebral, ischemia-reperfusion, gene expression, glucose, hyperglycemia, microarray, pigs
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-351620DOI: 10.1016/j.jstrokecerebrovasdis.2017.11.036ISI: 000428778400016PubMedID: 29306595OAI: oai:DiVA.org:uu-351620DiVA, id: diva2:1217404
Funder
Erik, Karin och Gösta Selanders FoundationAvailable from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-06-13Bibliographically approved

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Lindblom, Rickard P FMolnar, MariaIsraelsson, CharlotteWiklund, LarsLennmyr, Fredrik

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Lindblom, Rickard P FMolnar, MariaIsraelsson, CharlotteWiklund, LarsLennmyr, Fredrik
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Thoracic SurgeryAnaesthesiology and Intensive CareDevelopmental NeuroscienceDepartment of Medical SciencesScience for Life Laboratory, SciLifeLab
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Journal of Stroke & Cerebrovascular Diseases
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