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Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
2010 (Engelska)Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, nr 3, s. 163-168Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2010. Vol. 115, nr 3, s. 163-168
Nyckelord [en]
Brain ischemia, glucose, hyperglycemia, rat, reperfusion
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-130371DOI: 10.3109/03009734.2010.498592ISI: 000281013000002PubMedID: 20636251OAI: oai:DiVA.org:uu-130371DiVA, id: diva2:349440
Tillgänglig från: 2010-09-07 Skapad: 2010-09-07 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
Ingår i avhandling
1. Hyperglycemia in Experimental Cerebral Ischemia
Öppna denna publikation i ny flik eller fönster >>Hyperglycemia in Experimental Cerebral Ischemia
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.  

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2015. s. 86
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1089
Nyckelord
brain ischemia, cardiac arrest, cytokines, gene expression, glucose, hyperglycemia, microarray, oxidative stress, pigs, rats, reperfusion, resuscitation S100β
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Anestesiologi och intensivvård; Neurovetenskap
Identifikatorer
urn:nbn:se:uu:diva-247763 (URN)978-91-554-9216-8 (ISBN)
Disputation
2015-05-28, Enghoffsalen, Entrance 50, Akademiska Sjukhuset, Uppsala, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2015-05-07 Skapad: 2015-03-23 Senast uppdaterad: 2018-01-11

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