Glucocorticoid Receptor Blockers Pretreatment Did Not Improve Infarct Volume in Type-2 Diabetic Mouse Model of Stroke

Impaired glucocorticoid signaling in diabetes mellitus and its relation to suppressed immune function and hyperglycemia during acute stroke has been shown to be detrimental. Therefore, the aim of this study was to examine the effect of glucocorticoid receptor (GCR) blockers in a type-2 diabetic mouse model following hypoxia–ischemia (HI). We induced stroke in diabetic db/db and non-diabetic db/+ mice by unilateral common carotid artery ligation followed by 20 min of HI. Mice were pretreated with RU-486, GCRII blocker (40 mg/kg), intraperitoneally, the day before, during stroke and post-HI. Blood and brain samples were collected at 24 h post-HI to measure blood glucose, corticosterone and infarct size. Similarly, another set of mice was pretreated with RU-486 + spironolactone, GCR1 blocker (25 mg/kg) subcutaneously for a week before inducing stroke and during recovery. Samples were collected at 48 h post-HI for various analyses. RU-486 treatment did not lower the blood glucose significantly, but RU-486 + spironolactone decreased the blood glucose in db/db mice post-HI. However, none of the treatment groups decreased the ischemia-induced serum corticosterone level or infarct size. This study suggests that even though GCR blockers improve hyperglycemia, they did not improve the infarct volume.