Projects and Grants per year
Grants and Contracts Details
Description
Abstract
Moyamoya is a cerebrovascular condition in which the terminal ICA and its major branches undergo progres-
sive stenosis, leading to reduced blood flow to the brain. As a compensatory mechanism, an abnormal vascular
network of collateral arteries develop at the base of the brain within the lenticulostriate region. Symptoms include
hemorrhagic stroke, ischemic stroke, headache, transient ischemic attack, seizures, and cognitive impairment.
The small, tortuous arteries that develop in response to ischemia branch off the circle of Willis and are prone to
rupture, causing an intracranial hemorrhage, a major risk factor for morbidity and mortality of moyamoya patients.
The precise pathophysiology that leads to hemorrhage is not fully understood, but hemodynamic stress and
inflammation are thought to play an important role. We have worked to optimize the internal carotid artery ste-
nosis (ICAS) surgical method in mice to investigate the pathological changes that occur following stenosis. We
observe a significant decrease in diameter of the intracranial ICA, vascular wall thickening, vessel disruption in
the cortical watershed region, blood-brain barrier (BBB) permeability, neuroinflammation and the presence of
microbleeds. What is not known is how the effects of vessel stenosis prior to a large hemorrhagic event affect
post-hemorrhage recovery and risk of rebleeding. Therefore, we propose a continuation of our studies, with a
focus on neuroinflammation, BBB dysfunction, and cerebrovascular anatomical alterations. We hypothesize that
ICAS induces a cycle of pathology that includes chronic inflammation and vascular instability, which predisposes
blood vessels to an increased risk of bleeding. To test this hypothesis, we will combine our ICAS mouse model
with a model of intracerebral hemorrhage (ICH) and 1) define the inflammatory mechanisms that contribute to
intracranial bleeding, 2) identify the BBB permeability mechanisms that contribute to intracranial bleeding, and
3) quantify the anatomical cerebrovascular alterations that occur following ICAS and ICH in mice using microCT
imaging. We anticipate ICAS will sensitize the animals to experience an increased ICH-induced hematoma vol-
ume due, in part, to an increase in T cell expression, increased BBB permeability from MMP-9 activity, and
alterations in the lenticulostriate arteries, all of which make the tissue vulnerable to future bleeding events. In
addition to our animal studies, we will continue to enroll patients into our Moyamoya and Stroke Tissue and
Evaluation Repository (MASTER) study to increase our knowledge about what inflammatory and vessel-related
changes are occurring in our local moyamoya syndrome patient population.
Status | Finished |
---|---|
Effective start/end date | 7/30/21 → 6/30/22 |
Funding
- National Center for Advancing Translational Sciences
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.
Projects
- 1 Finished
-
Kentucky Center for Clinical and Translational Science - Institutional Career Development Core
Kelly, T., Arnett, D., Curry, T., DiPaola, R., Duncan, M., Evers, B. M., Giannone, P., Guy, R. K., Heath, E., Jicha, G., Kern, P., King, V., Lacy Leigh, M., Lephart, S., McLouth, L., Roberts, J., Samaan, M., Supinski, G., Talbert, J. & Williams, L.
National Center for Advancing Translational Sciences
8/15/16 → 6/30/22
Project: Research project