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Molnar, Maria
Publications (6 of 6) Show all publications
Lindblom, R. P., Molnar, M., Israelsson, C., Röjsäter, B., Wiklund, L. & Lennmyr, F. (2018). Hyperglycemia Alters Expression of Cerebral Metabolic Genes after Cardiac Arrest. Journal of Stroke & Cerebrovascular Diseases, 27(5), 1200-1211
Open this publication in new window or tab >>Hyperglycemia Alters Expression of Cerebral Metabolic Genes after Cardiac Arrest
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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.

Keywords
Cerebral, ischemia-reperfusion, gene expression, glucose, hyperglycemia, microarray, pigs
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-351620 (URN)10.1016/j.jstrokecerebrovasdis.2017.11.036 (DOI)000428778400016 ()29306595 (PubMedID)
Funder
Erik, Karin och Gösta Selanders Foundation
Available from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-06-13Bibliographically approved
Molnar, M., Bergquist, M., Larsson, A., Wiklund, L. & Lennmyr, F. (2014). Hyperglycaemia increases S100β after short experimental cardiac arrest. Acta Anaesthesiologica Scandinavica, 58(1), 106-113
Open this publication in new window or tab >>Hyperglycaemia increases S100β after short experimental cardiac arrest
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2014 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 1, p. 106-113Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Hyperglycaemia is associated with aggravated ischaemic brain injury. The main objective of this study was to investigate the effects on cerebral perfusion of 5 min of cardiac arrest during hyperglycaemia and normoglycaemia.

METHODS:

Twenty triple-breed pigs (weight: 22-29 kg) were randomised and clamped at blood glucose levels of 8.5-10 mM [high (H)] or 4-5.5 mM [normal (N)] and thereafter subjected to alternating current-induced 5 min-cardiac arrest followed by 8 min of cardiopulmonary resuscitation and direct current shock to restore spontaneous circulation.

RESULTS:

Haemodynamics, laser Doppler measurements and regional venous oxygen saturation (HbO2 ) were monitored, and biochemical markers in blood [S100β, interleukin (IL)-6 and tumour necrosis factor (TNF)] quantified throughout an observation period of 3 h. The haemodynamics and physiological measurements were similar in the two groups. S100β increased over the experiment in the H compared with the N group (P < 0.05). IL-6 and TNF levels increased across the experiment, but no differences were seen between the groups.

CONCLUSIONS:

The enhanced S100β response is compatible with increased cerebral injury by hyperglycaemic compared with normoglycaemic 5 min of cardiac arrest and resuscitation. The inflammatory cytokines were similar between groups.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-210633 (URN)10.1111/aas.12209 (DOI)000328156800014 ()24117011 (PubMedID)
Available from: 2013-11-12 Created: 2013-11-12 Last updated: 2017-12-06Bibliographically approved
Molnar, M. & Lennmyr, F. (2011). Neuroprotection by S-PBN in hyperglycemic ischemic brain injury. In: Basil S. Lewis, Moshe Y. Fugelman, David A. Halon (Ed.), Coronary artery disease: 2011 update: Proceedings of the 9th International Congress onCoronary Artery Disease. Paper presented at 9th International Congress on Coronary Artery Disease ICCAD 2011, Venice Italy, October 23-26 2011 (pp. 41-43). Bologna: Medimond
Open this publication in new window or tab >>Neuroprotection by S-PBN in hyperglycemic ischemic brain injury
2011 (English)In: Coronary artery disease: 2011 update: Proceedings of the 9th International Congress onCoronary Artery Disease / [ed] Basil S. Lewis, Moshe Y. Fugelman, David A. Halon, Bologna: Medimond, 2011, p. 41-43Conference paper, Published paper (Refereed)
Abstract [en]

Background: Hyperglycemia exacerbates focal ischemic brain damage supposedly through various mechanisms. One such mechanism is oxidative stress involving reactive oxygen and nitrogen species (RONS) production. Nitrones attenuate oxidative stress in various models of brain injury. Sulphonated nitrones are hydrophilic and highly feasible to administer in experimental settings. Sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) has been shown neuroprotective in experimental brain trauma. Together with the theories on increased oxidative stress in focal brain ischemia with concomitant hyperglycemia, we hypothesised that S-PBN might be neuroprotective under those circumstances as well.

Material and methods: The rats were made hyperglycemic by intraperitoneal bolus of glucose (2 g/kg) and then subjected to 90 min transient middle cerebral artery occlusion (MCAO). They were randomised to a therapeutic regime of S-PBN (47 mg/kg) or saline given intravenously. Neurological testing and tetrazolium red staining were performed after 1 day.

Results: S-PBN improved the neurological performance at day 1 both in Bederson score (1,3 +/- 0,8 vs. 2,7 +/- 0,48)(figure 1) and on the inclined plane [74,5% +/- 4,6 (S-PBN) vs. 66% +/- 8,3 (control) P< 0.05] (figure 2); but did not reduce the infarct size (figure 3). Physiological data did not differ between groups (table1).

Place, publisher, year, edition, pages
Bologna: Medimond, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-172309 (URN)000300222000008 ()978-88-7587-619-7 (ISBN)
Conference
9th International Congress on Coronary Artery Disease ICCAD 2011, Venice Italy, October 23-26 2011
Available from: 2012-04-04 Created: 2012-04-04 Last updated: 2012-04-04Bibliographically approved
Lennmyr, F., Molnar, M., Basu, S. & Wiklund, L. (2010). Cerebral effects of hyperglycemia in experimental cardiac arrest. Critical Care Medicine, 38(8), 1726-1732
Open this publication in new window or tab >>Cerebral effects of hyperglycemia in experimental cardiac arrest
2010 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, no 8, p. 1726-1732Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the effects of cardiac arrest on cerebral perfusion and oxidative stress during hyperglycemia and normoglycemia. Design: Experimental animal model. Setting: University laboratory. Subjects: Triple-breed pigs (weight, 22-27 kg). Interventions: Thirty-three pigs were randomized and clamped at blood glucose levels of 8.5-10 mM (high) or 4-5.5 mM (normal) and thereafter subjected to alternating current-induced 12-min cardiac arrest followed by 8 mins of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Measurements and Main Results: Hemodynamics, regional near-infrared light spectroscopy, regional venous HbO(2), and biochemical markers (Protein S100 beta, troponin I, F-2-isoprostanes reflecting oxidative stress and inflammation) were monitored and/or sampled throughout an observation period of 4 hrs. No significant differences were seen in hemodynamics or biochemical profile. The cerebral oxygenation by means of regional near-infrared light spectroscopy was higher in the hyperglycemic (H) than in the normal (N) group after restoration of spontaneous circulation (p < .05). However, tendencies toward increased protein S100 beta and 15-keto-dihydro-prostaglandin F-2 alpha were observed in the H group but were not statistically significant. Conclusions: The responses to 12-min cardiac arrest and cardiopulmonary resuscitation share large similarities during hyperglycemia and normoglycemia. The higher cerebral tissue oxygenation observed in the hyperglycemia needs to be confirmed and the phenomenon needs to be addressed in future studies.

Keywords
cardiac arrest, glucose, hyperglycemia, ischemia, oxidative stress, resuscitation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-135956 (URN)10.1097/CCM.0b013e3181e7982e (DOI)000280116500013 ()20562703 (PubMedID)
Available from: 2010-12-09 Created: 2010-12-09 Last updated: 2017-12-11Bibliographically approved
Molnar, M. & Lennmyr, F. (2010). Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats. Upsala Journal of Medical Sciences, 115(3), 163-168
Open this publication in new window or tab >>Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats
2010 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 3, p. 163-168Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Hyperglycemia exacerbates focal ischemic brain damage supposedly through various mechanisms. One such mechanism is oxidative stress involving reactive oxygen and nitrogen species (RONS) production. Nitrones attenuate oxidative stress in various models of brain injury. Sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) can be administered experimentally and has been shown to be neuroprotective in experimental brain trauma. AIMS OF THE STUDY: We hypothesized that S-PBN might be neuroprotective in hyperglycemic focal cerebral ischemia. MATERIAL AND METHODS: Rats were made hyperglycemic by an intraperitoneal bolus injection of glucose (2 g/kg) and then subjected to 90 min transient middle cerebral artery occlusion (MCAO). They were randomized to a therapeutic regime of S-PBN (156 mg/kg) or saline given intravenously. Neurological testing according to Bederson and tetrazolium red staining were performed after 1 day. RESULTS: S-PBN improved the neurological performance at day 1 both in Bederson score (1.3+/-0.8 versus 2.7+/-0.48) and on the inclined plane (74.5%+/-4.6 (S-PBN) versus 66%+/-8.3 (control), P<0.05) but did not reduce the infarct size. Physiological data did not differ between groups. CONCLUSION: S-PBN may improve neurological performance at short-term survival (1 day) in the present model of hyperglycemic-ischemic brain injury in rats. This effect appeared not to be primarily related to reduced infarct size.

Keywords
Brain ischemia, glucose, hyperglycemia, rat, reperfusion
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-130371 (URN)10.3109/03009734.2010.498592 (DOI)000281013000002 ()20636251 (PubMedID)
Available from: 2010-09-07 Created: 2010-09-07 Last updated: 2017-12-12Bibliographically approved
Molnar, M., Lindblom, R., Israelsson, C., Fridman, B., Wiklund, L. & Lennmyr, F.Differential regulation of cerebral metabolic genes after hyperglycemic and normoglycemic cardiac arrest.
Open this publication in new window or tab >>Differential regulation of cerebral metabolic genes after hyperglycemic and normoglycemic cardiac arrest
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(English)Manuscript (preprint) (Other academic)
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-248097 (URN)
Note

Author 1 and 2 contributed equally to this manuscript

Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2015-07-07
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