7 research outputs found
Cardiometabolic Disease Results in Sexâ and AgeâDependent Cerebrovascular Degeneration and Arteriolar Morphological Changes
ABSTRACT In the past 20 years, no drug therapies have been successfully translated into human use for intracerebral hemorrhage (ICH), the most devastating stroke subset. One likely factor is lack of effective animal models of human disease including common comorbidities, such as hypertension and diabetes. We evaluated the cardiometabolic rodent model, (mRen2)27, where overexpression of Ren2 results in extreme hypertension, glucose intolerance and obesity, as an appropriate ICH model. Methods: Sprague Dawley (SD) and (mRen2)27 rats were sacrificed at 14â, 32â, and 52âweeks. Brains were sectioned sagittally at 5Â ÎŒm. Wholeâbrain sections were stained using Hematoxylin & Eosin (H&E) and Van Geison (VG) collagen staining to visualize the pial blood vessels. Wallâtoâlumen ratios for vessels were calculated and compared using a student tâtest to determine significance. Results: There was no significant difference in arteriolar morphology at 14âweeks between male SD and mRen animals (SD, n=16 and mRen, n=16). At 32âweeks, there was a significant difference in mRen male rats (SD, n=13 and mRen, n=17; p<0.0001), with significantly increased wall thickness and decreased Lumen size in the mRen animals (increased W:L ratio). However, at this timeframe, there was no significant difference between the female SD and mRen cohorts (SD, n=6 and mRen, n=8). At 52âweeks, there was a significant increase in W:L ratios in both male (SD, n=4 and mRen, n=7; p<0.01) and female (SD, n=9 and mRen, n=8; p<0.05) mRen animals compared to control. Conclusion: The (mRen2)27 cardiometabolic animal model demonstrates ageârelated sex changes in the wall:lumen ratio of cerebral vasculature consistent with cerebrovascular disease seen in ischemic and hemorrhagic stroke patients. Males develop these vascular changes earlier than females, but both sexes in this model develop cerebral vascular changes by 1Â year of age. The (mRen2)27 model appears to recapitulate human disease and sex differences, and may serve as an appropriate translational model of ICH