Single-microvessel occlusion produces lamina-specific microvascular flow vasodynamics and signs of neurodegenerative change

Recent studies have highlighted the importance of understanding the architecture and function of microvas-culature, 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 ar-chitecture and hemodynamics after single-capillary occlusion reveals distinct changes upstream vs. down-stream 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 neuro-degenerative disease.

Automated summary

Recent studies have emphasized the significance of understanding microvascular architecture and function, as dysfunction in these small blood vessels may be a cause of neurodegenerative diseases. In this study, a precise and rapid laser-induced photothrombosis method was used to block individual capillaries and investigate the effects on blood flow and nearby neurons. The analysis showed distinct changes in microvascular structure and hemodynamics upstream and downstream of the occluded capillaries, indicating regional flow redistribution and local blood-brain barrier leakage. Focal ischemia induced by capillary occlusion around specific neurons resulted in significant and speedy alterations in dendritic architecture. Additionally, occlusions at different depths within the same vascular network had varying effects on flow profiles in different layers. These findings suggest laminar-scale regulation differences in microinfarct response and propose that greater impacts on microvascular function may contribute to cognitive decline in neurodegenerative diseases.