Abstract WP297: A Mouse Model of Cerebral Microbleeds
Cerebral microbleeds are microscopic hemorrhages with deposits of blood products in the brain that can be visualized with MRI. Microbleeds are increased with age and in diseases such as cerebral amyloid angiopathy, hypertension, and stroke. There are few studies of either a) pathological correlates of cerebral microbleeds or b) imaging microscopic hemorrhage in brain tissue. The existing animal models of cerebral microbleeds involve transgenic mice (e.g. Tg2576) that spontaneously over-express β-amyloid, mimicking cerebral amyloid angiopathy. However, these models have limited use due to the fact that a) microbleeds may develop independent of amyloid deposition and b) the transgenic animals may require two years to fully develop microbleeds. In the current study, we used lipopolysaccharide (LPS) to induce cerebral microscopic hemorrhages over the course of several days. In this model, adult C57B6 mice (3 months of age) were injected with LPS (5mg/kg ip) or vehicle (phosphate buffered saline) at baseline and at 24 hr, and animals were sacrificed two days after initial injection. Mouse brains were analyzed for fresh hemorrhage using hematoxylin and eosin (H&E) staining, iron deposition using Prussian blue staining, and blood-brain barrier (BBB) permeability by measuring sodium flouorescein (NaF) content. H&E staining revealed small fresh hemorrhages visible grossly and microscopically in all animals treated with LPS, but not in control animals. Prussian blue staining revealed markedly increased iron deposition with LPS treatment, with positive stains in cerebral cortex, midbrain, and hippocampus regions. Quantification of Prussian blue staining revealed that LPS induced more than four-fold increase in number of positive stained foci (p<.05 vs control). BBB permeability to NaF was increased from 2.9 ± 0.3 in control to 8.2 ± 1.8 ug NaF/g brain tissue in LPS-treated animals (p<.05 vs control). In conclusion, this mouse model shows rapid production of cerebral microscopic hemorrhage, is associated with BBB dysfunction, and may be useful to study mechanistic and intervention strategies of cerebral microbleeds.
- © 2012 by American Heart Association, Inc.