uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Hyperglycemia in Experimental Cerebral Ischemia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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 [en]
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: urn:nbn:se:uu:diva-247763ISBN: 978-91-554-9216-8 (print)OAI: oai:DiVA.org:uu-247763DiVA: diva2:798698
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
List of papers
1. Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats
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, 163-168 p.Article 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.

Keyword
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
2. Cerebral effects of hyperglycemia in experimental cardiac arrest
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, 1726-1732 p.Article 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.

Keyword
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
3. Hyperglycaemia increases S100β after short experimental cardiac arrest
Open this publication in new window or tab >>Hyperglycaemia increases S100β after short experimental cardiac arrest
Show others...
2014 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 1, 106-113 p.Article 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
4. 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
Show others...
(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

Open Access in DiVA

fulltext(1214 kB)285 downloads
File information
File name FULLTEXT01.pdfFile size 1214 kBChecksum SHA-512
475944b3ddebc67eba9b2f639352ac0b15caeee6d92556aa12b2e91f6e51167583c1081e5de7627472b1dc51cf25c5d4b22bb108b697f9c1fa5e2177115657a0
Type fulltextMimetype application/pdf
Buy this publication >>

By organisation
Anaesthesiology and Intensive Care
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 285 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1115 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf