Estrogen Decreases Infarct Size After Temporary Focal Ischemia in a Genetic Model of Type 1 Diabetes Mellitus Editorial Comment

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Stroke (Impact Factor: 5.72). 12/2000; 31(11):2701-6. DOI: 10.1161/01.STR.31.11.2701
Source: PubMed

ABSTRACT It is unclear how genetic type 1 diabetes mellitus (DM) influences infarct size when blood glucose is tightly controlled. The aim of this study was to determine the effect of genetic type 1 DM, as occurs in BB rats, on infarct size after transient unilateral middle cerebral artery occlusion (MCAO) in male and female rats. In addition, studies suggest that male type 1 DM rats have a higher incidence of end-organ complications than do females. A second aim of this study was to determine the effect of chronic 17beta-estradiol (E(2)) administration on infarct size in male BB rats.
Diabetic male (MDiab, n=14) and female (FDiab, n=8) BB rats were studied 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) received subcutaneous 25 microg E(2) implants 7 to 10 days before MCAO. Rats underwent 1 hour of MCAO followed by 22 hours of reperfusion. Physiological variables were controlled among groups, and the intraischemic laser Doppler flow signal was reduced similarly in all animals. Infarction volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining and image analysis.
Preischemic blood glucose was 94+/-5, 127+/-13, 90+/-15, 63+/-18, 122+/-8, and 81+/-14 mg/dL in MWist, FWist, MDiab, FDiab, MWist+E(2), and MDiab+E(2) rats, respectively (mean+/-SE). Intraischemic laser Doppler flow was reduced to 20% to 25% of baseline in all groups. Striatal infarct size (percentage of ipsilateral caudate putamen) was increased in male diabetic rats relative to nondiabetic MWist rats (41+/-3% versus 28+/-3%). Striatal injury 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 estrogen treatment reduced cortical and striatal infarction in MDiab+E(2) rats compared with untreated MDiab rats.
Type 1 DM is associated with increased infarct size after temporary MCAO, despite tight control of blood glucose. The deleterious effect of DM is evident only in males rats; female diabetic BB rats sustain small infarcts. Chronic E(2) treatment reduced injury in the male BB rat, providing neuroprotection even in the presence of DM. These data suggest that genetic diabetes even with mild glucose elevation plays a role in determining neuropathology in experimental stroke. However, factors such as reproductive steroids also determine outcome in DM stroke.

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    • "Diabetes impairs outcome in rodent models of focal cerebral ischemia (Bomont and MacKenzie 1995). Interestingly, brain injury and inflammation in diabetic models can be reversed by angiotensin II type 1 receptor (AT(1)-R) antagonist, PPARγ agonist, administration of 17β-estradiol, IGF-1, aspirin and niacin (B3 vitamin) even at high blood glucose levels, highlighting the potential role of inflammatory mechanism in diabetes-induced exacerbation of brain injury (Kusaka et al. 2004; Toung et al. 2000; Tureyen et al. 2007; Rizk et al. 2007; Wang et al. 2009; Ye et al. 2011). Brain injury and neurological outcome are exacerbated after cerebral ischemia in rodent models of hypertension, which can mostly (although not uniformly (Porritt et al. 2010)) be reversed by blood pressure lowering drugs (Elewa et al. 2007; Kozak et al. 2008). "
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