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

Direct link
Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats
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, Anaesthesiology and Intensive Care.
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.

Place, publisher, year, edition, pages
2010. Vol. 115, no 3, 163-168 p.
Keyword [en]
Brain ischemia, glucose, hyperglycemia, rat, reperfusion
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-130371DOI: 10.3109/03009734.2010.498592ISI: 000281013000002PubMedID: 20636251OAI: oai:DiVA.org:uu-130371DiVA: diva2:349440
Available from: 2010-09-07 Created: 2010-09-07 Last updated: 2015-07-07Bibliographically approved
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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1089
brain ischemia, cardiac arrest, cytokines, gene expression, glucose, hyperglycemia, microarray, oxidative stress, pigs, rats, reperfusion, resuscitation S100β
National Category
Research subject
Anaesthesiology and Intensive Care; Neuroscience
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)
Available from: 2015-05-07 Created: 2015-03-23 Last updated: 2015-07-07

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Molnar, MariaLennmyr, Fredrik
By organisation
Anaesthesiology and Intensive Care
In the same journal
Upsala Journal of Medical Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
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

Altmetric score

Total: 140 hits
ReferencesLink to record
Permanent link

Direct link