Abstract W P213: Leptomeningeal Collateral Growth Is Impaired in Type 2 Diabetic Mice.
BACKGROUND: Leptomeningeal anastomoses are the most important collateral pathways, especially after middle cerebral artery (MCA) occlusion, and determine the severity of subsequent ischemic injury of the brain. We previously reported that hypertension impairs leptomeningeal arteriogenesis. Diabetes is also a major vascular risk factor and increases stroke incidence. We hypothesized that arteriogenesis of leptomeningeal anastomoses is also impaired in diabetes.
METHODS: Male BKS.Cg-m+/+Leprdb/J (db/db) and the non-diabetic and lean heterozygote littermates(db/+) were used. To investigate the influence of hyperglycemia itself, male C57BL/6 mice injected with streptozotocin(STZ,250mg/kg) intraperitoneally 1week before surgery were also used. All types of mice were assigned to the left common carotid artery occlusion(CCAO) group and the sham CCAO group. After 14 days of the surgery, latex perfusion was performed to visualize the leptomeningeal anastomoses and mesure the vessel diameters(n=5, each group), or the left MCA was occluded using electrocoagulation to evaluate the infarct size with TTC staining(n=7, each group).
RESULTS: In db/+ mice, there were significant increase of leptomeningeal collateral vessel diameters in response to CCAO(CCAO,33.7±1.2μm vs. sham,26.5±1.0μm, P<0.01) and infarct size was significantly attenuated, especially in the cerebral cortex, in the CCAO group compared with the sham group, which was in agreement with our previous study in normal rodents. In contrast, in db/db mice, there were no significant differences in the vessel diameters between the CCAO group and the sham group(27.9±1.0μm vs.26.6±1.0μm) and no reductive effect of infarct size attribute to leptomeningeal arteriogenesis. In STZ induced diabetic mice, there were significant increase of the vessel diameters(29.1±1.1μm vs. 23.6±0.7μm, P<0.01) and significant reduction of infarct size in response to CCAO.
CONCLUSIONS: Arteriogenesis of leptomeningeal anastomoses is impaired in db/db mice, but is not impaired in STZ induced diabetic mice. These results suggest that the mechanism of impairment of arteriogenesis is not due to only hyperglycemia.
Author Disclosures: T. Yukami: None. Y. Yagita: None. A. Watanabe: None. T. Sasaki: None. H. Mochizuki: None. K. Kitagawa: None.
- © 2014 by American Heart Association, Inc.