Hyperglycemia in Experimental Cerebral Ischemia

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: 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 S100? and 15-keto-dihydro-prostaglandin F2? 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 S100? 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.