Biophysical and Biochemical Modulation of Cerebral Capillary Blood Flow: Effects of Lipids, Cholesterol, and Drag-Reducing Polymers on Capillary Function
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Authors
Franco, Cristian
Issue Date
2025
Type
Dissertation
Language
en_US
Keywords
Alternative Title
Abstract
The cerebral vascular network is complex and vast, as it supplies constant resources to the neural tissue, as well as removing waste. The complexity of the vasculature lies in its structure, as it is divided into distinct regions with different functions and purposes: arteries, arterioles, capillaries, and veins. This complexity allows for mechanisms to maintain blood flow, such as pressure-induced tone generation, shear stress mechanotransduction, and neurovascular coupling. This allows for fine-tuned control of blood flow towards the metabolically active tissue; therefore, small deficits can lead to a major negative impact on neuronal function. Fine-tuned control of blood flow is performed by pericytes, which can control the diameter of multiple vessels along the capillaries. To determine the impact of pericytes on blood flow, the "Capillary Triangle method" was developed to quantify and predict the flow of RBCs by taking into account the diameter and angle of deviation. Through photo stimulation, RBCs were redirected by altering the triangle characteristics to influence blood flow. To further elucidate the flow of blood within the capillary network, intraluminal viscosity was increased in disease states to determine the impact on fluid flow. It was found to have a significant effect on shear stress mechanotransduction, activating eNOS and inhibiting pressure-induced tone generation. Additionally, HFD also caused endothelial remodeling, resulting in reduced eNOS activation in the arterioles but not within the deep capillary bed. The impact of high plasma viscosity on endothelial function and remodeling could play a potential role in the development of dementias. To determine how the vasculature changes in dementia, Alzheimer's mice were used and stained with cholesterol labels, revealing distinct meso domains throughout the vasculature. These domains were shown to play a role in amyloidogenesis and Aβ aggregation. Patients with Alzheimer's and other dementias are very likely to develop thrombi and emboli, which cause clots within the capillary network. To manage this, DRPs are suggested to be used to minimize the coagulation of blood and increase cerebral blood flow. Sepsis was used to maximize coagulation and decrease blood flow, and DRPs were shown to lubricate the blood enough to prevent coagulation from endothelial activation. Taken together, the data support the importance of cerebral blood flow in the context of dementia and provide novel mechanisms to treat and prevent the development of dementias.