Title : Single microvessel occlusion technology (PLP) produces lamina-specific microvascular flow effects and neuronal degeneration
Abstract:
There is increasing recognition that dysfunctions of microvasculature in the brain may underlie neurodegenerative disease. To understand the functional architecture of cortical microvasculature, we developed a highly precise photothrombosis method (ULPT) to occlude single microcapillaries in distinct cortical layers, and then quantitatively studied effects on vasodynamics in the upstream and downstream branchlets of the micro-occlusion. Our results showed that such occlusion led to rapid regional flow redistribution and local downstream BBB leakage, as well as dramatic changes in neuronal dendritic architecture and neuronal degeneration. Interestingly, compared to layer 4, layers 2/3 exhibited significantly less flow redistribution, suggesting cortical feedback recipient layers may be more susceptible to micro-occlusion damage. This new precision model of microvascular ischemia revealed, for the first time, laminar distinctions in micro-infarct response, and raised the possibility that relatively greater impact on on micro-capillary function contribute to cognitive decline in neurodegenerative disease?
What will audience learn from your presentation?
This work provides novel and quantitative understanding of microvascular function in neurodegenerative disease:
- Novel precise micro-occlusion method: For the first time, we established single microvessel occlusion for depths up to 815μm in cortex and a method to study layer-specific microvascular flow.
- Single neurons are maintained by a few (1-3) local capillaries: Using this method, we show in vivo that occlusion of a few (2-3) neighboring capillaries leads to severe neurodegneration.
- Laminar-specific flow effects: Vascular flow in laminae 2/3 (feedback recipient layers) appears more susceptible to micro-occlusion, suggesting a novel microvascular basis for feedback-related cognitive decline in neurovascular disease.