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Differential regulation of cerebral metabolic genes after hyperglycemic and normoglycemic cardiac arrest
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 Surgical Sciences, Thoracic Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Science for Life Laboratory, SciLifeLab.
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(English)Manuscript (preprint) (Other academic)
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-248097OAI: oai:DiVA.org:uu-248097DiVA: diva2:798661
Note

Author 1 and 2 contributed equally to this manuscript

Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2015-07-07
In thesis
1. Hyperglycemia in Experimental Cerebral Ischemia
Open this publication in new window or tab >>Hyperglycemia in Experimental Cerebral Ischemia
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cerebral ischemia is a life-threatening condition associated with a substantial morbidity and mortality. Hyperglycemia, a common coexisting phenomenon in both stroke and cardiac arrest (CA), may further aggravate ischemic brain injury. To date, the therapeutic possibilities are lim-ited and the search for new treatment modalities is warranted. One aspect of such a research could be to better understand the cerebral pathogenesis induced by hyperglycemic ischemia-reperfusion.

We investigated the combination of ischemia and hyperglycemia in two experimental models of stroke and CA. The aims were to test the neuroprotective potential of the sulfonated nitrone 2-sulfophenyl-N-tert-butylnitrone (S-PBN) in focal hyperglycemic cerebral ischemia (1), to outline the short-terms effects of hyperglycemia in prolonged (2) and short CA (3) and to performed a global transcriptome analysis of brain from hyperglycemic and normoglycemic CA (4).

In a stroke model rats were made hyperglycemic prior to transient middle cerebral artery oc-clusion and randomized to S-PBN or saline. We found that S-PBN may ameliorate hyperglyce-mic-ischemic brain damage by improving the neurological performance after 1 day of survival, but did not reduce the infarct size.

To study the cerebral oxidative state and perfusion after CA, pigs were randomized and clamped at blood glucose levels of 8.5 ̶ 10.0 mmol/L (high) and 4.0 ̶ 5.5 mmol/L (normal), sub-jected to 12 ̶ min of CA, followed by 8 min of cardiopulmonary resuscitation (CPR), and ob-served for 180 min.

Increased oxygenation was found at higher glucose levels measured by near-infrared light spec-troscopy after CA. Tendencies toward increased protein S100β and 15-keto-dihydro-prostaglandin F2α were observed in the hyperglycemic group.

We hypothesized that in combination with a brief period of CA, the preischemic hyperglycemia would worsen the cerebral injury compared with normoglycemia. We used a glycemic protocol similar to that in Paper II, whereby pigs were subjected to 5 ̶ min of CA, followed by 8 min of CPR, and observed for 180 mins. An increased level of the cerebral marker S100β was found in hyperglycemic pigs compared with normoglycemic pigs after CA.

Global transcriptome analysis using microarray analysis revealed a different early metabolic gene expression in hyperglycemic CA compared with normoglycemic CA.  

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 86 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1089
Keyword
brain ischemia, cardiac arrest, cytokines, gene expression, glucose, hyperglycemia, microarray, oxidative stress, pigs, rats, reperfusion, resuscitation S100β
National Category
Neurosciences
Research subject
Anaesthesiology and Intensive Care; Neuroscience
Identifiers
urn:nbn:se:uu:diva-247763 (URN)978-91-554-9216-8 (ISBN)
Public defence
2015-05-28, Enghoffsalen, Entrance 50, Akademiska Sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2015-05-07 Created: 2015-03-23 Last updated: 2015-07-07

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Molnar, MariaLindblom, RickardWiklund, LarsLennmyr, Fredrik

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Anaesthesiology and Intensive CareThoracic SurgeryDepartment of NeuroscienceScience for Life Laboratory, SciLifeLab
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