Differential regulation of cerebral metabolic genes after hyperglycemic and normoglycemic cardiac arrest

Severe cerebral ischemia caused by events such as ischemic stroke or cardiac arrest is a relatively common and life-threating condition. Those who survive frequently suffer from significant cerebral dysfunction, often with poor outcome. To date the treatment options are limited. Concomitant hyperglycemia is frequently perceived both in focal and global transient ischemia, augmenting the ischemic brain injury as revealed by experimental and clinical studies. The aim with the current study was to improve the understanding of the pathogenesis behind how concomitant hyperglycemia can augment the cerebral injury seen after cerebral ischemia. To that end we performed a global transcriptome analysis of brains from hyperglycemic and normoglycemic pigs after transient global ischemia. Pigs were openly 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 cardiac arrest of 5 min followed by 8 min of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Global expression profiling of the cortex using microarrays was performed in both groups.