Estrogen decreases infarct size after temporary focal ischemia in a genetic model of type 1 diabetes mellitus

Background and Purpose-It is unclear how genetic type 1 diabetes mellitus ( DM) influences infarct size when blood glucose is tightly controlled. The a im of this study was to determine the effect of genetic type I DM, as occur s in BE rats, on infarct size after transient unilateral middle cerebral ar tery occlusion (MCAO) in male and female rats. In addition, studies suggest that male type 1 DM rats have a higher incidence of end-organ complication s than do females. A second aim of this study was to determine the effect o f chronic 17 beta -estradiol (E-2) administration on infarct size in male B E rats. Methods-Diabetic male (MDiab, n=14) and female (FDiab, n=8) BE rats were st udied and compared with background strain Wistar rats (MWist, n=16; FWist, n=14). Two additional male cohorts (MWist+E-2, n=15; MDiab+E-2, n=14) recei ved subcutaneous 25 mug E-2 implants 7 to 10 days before MCAO. Rats underwe nt 1 hour of MCAO followed by 22 hours of reperfusion. Physiological variab les were controlled among groups, and the intraischemic laser Doppler flow signal was reduced similarly in all animals. Infarction volume was evaluate d by 2,3,5-triphenyltetrazolium chloride staining and image analysis. Results-Preischemic blood glucose was 94+/-5, 127+/-13, 90+/-15, 63+/-18, 1 22+/-8, and 81+/-14 mg/dL in MWist, FWist, MDiab, FDiab, MWist+E-2, and MDi ab+E-2 rats, respectively (mean+/-SE). Intraischemic laser Doppler flow was reduced to 20% to 25% of baseline in all groups. Striatal infarct size (pe rcentage of ipsilateral caudate putamen) was increased in male diabetic rat s relative to nondiabetic MWist rats (41+/-3% versus 28+/-3%). Striatal inj ury was not increased in FDiab rats, and infarction volume was smaller than that in FWist rats (23+/-4% in FWist Versus 13+/-3% in FDiab). Chronic est rogen treatment reduced cortical and striatal infarction in MDiab+E-2 rats compared with untreated MDiab rats. Conclusions-Type 1 DM is associated with increased infarct size after tempo rary MCAO, despite tight control of blood glucose. The deleterious effect o f DM is evident only in males rats; female diabetic BE rats sustain small i nfarcts. Chronic E-2 treatment reduced injury in the male BE rat, providing neuroprotection even in the presence of DM. These data suggest that geneti c diabetes even with mild glucose elevation plays a role in determining neu ropathology in experimental stroke. However, factors such as reproductive s teroids also determine outcome in DM stroke.