Abstract
Recent studies have highlighted the importance of understanding the architecture and function of microvasculature, and dysfunction of these microvessels may underlie neurodegenerative disease. Here, we utilize a high-precision ultrafast laser-induced photothrombosis (PLP) method to occlude single capillaries and then quantitatively study the effects on vasodynamics and surrounding neurons. Analysis of the microvascular architecture and hemodynamics after single-capillary occlusion reveals distinct changes upstream vs. downstream branches, which shows rapid regional flow redistribution and local downstream blood-brain barrier (BBB) leakage. Focal ischemia via capillary occlusions surrounding labeled target neurons induces dramatic and rapid lamina-specific changes in neuronal dendritic architecture. Further, we find that micro-occlusion at two different depths within the same vascular arbor results in distinct effects on flow profiles in layers 2/3 vs layer 4. The current results reveal laminar-scale regulation distinctions in microinfarct response and raise the possibility that relatively greater impacts on microvascular function contribute to cognitive decline in neurodegenerative disease.
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