Roles of Astrocytic NF-kB signal transduction on neurovascular coupling in Alzheimer mouse model with oxidative stress-induced microvascular pathology

Study of microvascular pathology and function in AD has been limited, in part, by a dearth of mixed pathology preclinical models and the relatively infrequent use of high-resolution intravital imaging approaches. Recently, we characterized an oxidative stress-mediated thrombotic insult protocol in mouse neocortical arterioles, via photoactivation of IV injected Rose Bengal dye (RB) and modified it for targeting individual capillaries. The major advantage of this novel vascular oxidative stress model is that vessel stalls, occlusion, and hemorrhages can be followed in single capillaries in living mice, in real time, using two-photon imaging. We proposed this approach in our recent R21 that we previously submitted, and the reviewers commented that the mechanistic studies in vivo are underdeveloped. Thus, we aim to combine this technology with a cell type specific approach to investigate the roles of astrocytic NF-κB signaling pathway on vascular function in AD mouse model.