Abstract WMP111: Stroke and Alzheimer’s Disease: Shared Mechanisms of Vascular Disruption
Recent evidence suggests that Alzheimer’s disease is a vascular disorder that can be accelerated by ischemic stroke. We propose that the underlying pathophysiology accelerating degenerative changes is due to blood brain barrier disruption following ischemia. A transient middle cerebral artery occlusion suture model was used in triple-transgenic AD mice and C57/Bl6 wild type controls. A separate triple-transgenic AD mice group was used for sham control. The middle cerebral artery was occluded for 1 hour followed by reperfusion. Mice were evaluated for sickness behavior and received a modified neurologic score. 5 hours after reperfusion, blood brain barrier tracers (Texas red, IcG, and AIB1) were injected i.v. into the femoral vein and allowed to circulate for 10 minutes. H&E, Cresyl Violet, and Thioflavin were used to stain sections of the brain for areas of degeneration. Images were obtained by quantitative fluorescent and bright-field microscopy. One-way ANOVA with Tukey’s post-hoc comparison was used to compare between groups. P<0.05 was considered statistically significant. A statistically significant difference between groups was seen for blood brain barrier permeability following ischemia and reperfusion. Triple-transgenic AD mice had a 2-fold increase in Texas red and a 4-fold increase in AIB1 at 5 hours after reperfusion. No significant differences were seen in the control groups. H&E staining revealed nuclear fragmentation, chromatolysis, and vacuolization in the ipsilateral cortex of the triple-transgenic AD mice exposed to stroke. Limited areas of necrosis were seen in the C57/Bl6 controls. A significant increase in thioflavin staining was seen post-stroke in the triple-transgenic AD mice. The amyloid distribution was perivascular and significantly increased compared to the triple-transgenic AD sham mice. Triple-transgenic AD mice had a worse sickness score (avg. 13) compared to C57/Bl6 controls (avg. 17). Stroke and Alzheimer’s disease share similar vascular mechanisms related to blood brain barrier disruption. We show that blood brain barrier disruption post-stroke accelerates degenerative changes. Targeting blood brain barrier disruption as a treatment approach may prove promising and warrants continued investigation.
Author Disclosures: B. Lucke-Wold: None. A. Logsdon: None. A. Mohammad: None. C. Adkins: None. X. Ren: None. J. Huber: None. C. Rosen: None. J. Simpkins: None. P. Lockman: None.
- © 2016 by American Heart Association, Inc.