(VP088) QUANTIFICATION OF NEUROVASCULATURE CHANGES IN A POST-HEMORRHAGIC STROKE ANIMAL-MODEL

Background: Hemorrhagic stroke (HS) mortality reaches an astounding 65% at one-year. Defining cerebrovascular changes associated with HS is pivotal for the development of novel pharmacological treatments. Our study used high-resolution imaging technology and vascular perfusion casting to study the neurovascular network differences in a hemorrhagic stroke animal-model.

METHODS AND RESULTS: Stroke-prone spontaneously hypertensive rats (SHRsp) were divided into pre-stroke (n=12) controls and post-stroke (sampled at physical signs of stroke; n=12). Evan’s Blue (EB) was infused through the femoral artery prior to infusion of Vascupaint (MediLumineTM), a novel bismuth vanadate latex casting compound used to opacify microvasculature. 3D visualization of the neurovascular network was achieved using micro-CT imaging and data was analyzed using bundled Skyscan 1176 software (Bruker). Additionally, optical fluorescence imaging (GE/ART Optix) was performed to examine the relationship between EB dye extravasation and alterations in surrounding vasculature. Post-stroke animals exhibited EB dye extravasation and decreased Vascupaint perfusion macroscopically, compared to pre-stroke brains. The 3D-rendering of brain vasculature post-stroke indicated decreased percent vascular volume, connectivity, and branching. Further, the EB fluorescence intensity data macroscopically correlated with stroke site and severity. Findings trend towards a positive hypothesis, demonstrating that there is a reduction in intact intracerebral vasculature post-stroke, compared to pre-stroke, as evidenced by mean 3D analysis parameters such as percent vessel volume (2.937 pre-stroke; 0.691 post-stroke, p< 0.001) and fractal dimension (1.888 pre-stroke; 1.392 post-stroke, p< 001).

Conclusion: Our study established a standardized method for the preparation, imaging and measurement of cerebral blood supply through use of a novel casting compound, preclinical micro-CT and fluorescence imaging, in a unique stroke-prone animal-model. The data acquired demonstrates that rat brain arteries, veins and capillaries can be successfully perfused to quantify changes in neurovasculature post-hemorrhagic stroke. Advances in visualization of cerebrovascular changes in HS is critical for the potential development of new treatment strategies.