Abstract W P200: Human Albumin Improves Leptomeningeal Collateral Flow Following Experimental Stroke in Type 2 Diabetic Mice
Introduction: Type 2 diabetes mellitus (T2DM) is major risk factor of ischemic stroke and is associated with poor outcome after stroke. Previously we found that T2DM mice exhibited impaired leptomeningeal collateral flow recruitment after distal middle cerebral artery occlusion (MCAO). Human albumin has emerged as a potent neuroprotective agent in experimental stroke due to its multiple salutary actions. However, the effect of albumin on collateral flow in T2DM subjects is yet to be determined.
Methods: Distal MCAO was induced in male db/db and db/+ mice (19-22 weeks of age). To evaluate the effect of albumin on collateral flow recruitment, mice were treated with 25% albumin or saline 2h after stroke. Doppler optical coherence tomography was used to quantify the MCA flow direction, flow velocity and vessel diameter before and after treatment. The chosen regions of interest of MCA network were classified according to branching order as segment 1 (seg1), seg2 and seg3, with seg1 most proximal to ACA while most distal to MCA. 5-10 points corresponding to the same location of each segment were selected for quantification. The infarction volume was assessed 7 days after stroke.
Results: Albumin treatment significantly improved MCA flow velocity in db/db as well as db/+ mice (albumin effect: P<0.005/ P <0.05/ P <0.05 per seg1/seg2/seg3; genotype effect: NS in all segments; Two-way-ANOVA). The albumin effect on collateral flow velocity in seg 2 and seg 3 of db/+ mice is less pronounced compared to that in db/db mice, due to an already robust retrograde flow from ACA to MCA in the former after MCAO. In contrast, albumin did not have an effect on MCA diameter in all segments of either group. Further, albumin treatment reduced infarct size in both groups of mice (db/db: albumin: 2.2±0.5%, saline: 5.0±0.4%, P<0.01; db/+: albumin: 1.9±0.4%; saline: 3.3±0.5%, P<0.05).
Conclusion: Albumin enhances leptomeningeal collateral flow recruitment during the acute phase of stroke in both type 2 diabetic mice and normoglycemice control mice, coincided with a reduction in stroke size. Our data suggest that albumin is a viable option for the treatment of a diverse population of stroke patients including those with vascular risk factor.
Author Disclosures: Y. Akamatsu: None. C. Lee: None. J. Liu: None.
This research has received full or partial funding support from the American Heart Association, Western States - Alaska, Arizona, California, Hawaii, Idaho, Montana, Nevada, Oregon, Utah, Washington.
- © 2014 by American Heart Association, Inc.