THESIS
2014
iv leaves, v-xi, 79 pages : illustrations ; 30 cm
Abstract
Intracranial aneurysm is a high-incidence disorder with many latent patients. It might lead to possibly lethal complications including ischemic stroke and subarachnoid hemorrhage. Various neurosurgical methods are studied and developed to treat the disease and prolong the life span of patients. Modern treatment technologies include endovascular coiling and flow diverting, which basically introduce thrombosis in aneurysm by flow reduction. This study aims to understand the tissue remodeling during aneurysm progression using an animal model, especially in the presence of endovascular thrombus. Aneurysm development is characterized by its structure, morphology and dimension, while the remodeling activity is to be identified. The thrombus formation prior to aneurysm healing is also characte...[
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Intracranial aneurysm is a high-incidence disorder with many latent patients. It might lead to possibly lethal complications including ischemic stroke and subarachnoid hemorrhage. Various neurosurgical methods are studied and developed to treat the disease and prolong the life span of patients. Modern treatment technologies include endovascular coiling and flow diverting, which basically introduce thrombosis in aneurysm by flow reduction. This study aims to understand the tissue remodeling during aneurysm progression using an animal model, especially in the presence of endovascular thrombus. Aneurysm development is characterized by its structure, morphology and dimension, while the remodeling activity is to be identified. The thrombus formation prior to aneurysm healing is also characterized. Male Sprague-Dawley rats are used to build the aneurysm model. Right common carotid arteries (RCCAs) are bathed in a solution of porcine pancreatic elastase in 0.1 M phosphate-buffered solution (PBS) (10 U/ml) for 20 minutes and then ligated at distal end. The left common carotid arteries (LCCAs) are bathed in PBS solution to create a control group. The tissue morphology is studied using Toluidine Blue O and Hematoxylin and Eosin (H&E) stain, while immunological protocols are applied to identify the components in tissue remodeling. The Martius, Scarlet and Blue (MSB) method is also used for the analysis of thrombus. From Day 0 to Day 7 after the aneurysm creation surgery, the aneurysm model is filled with thrombus and the cross-sectional diameter increases until Day 28. The study on thrombus also shows higher fibrin concentration at the distal end and total concentration of fibrin decreases at Day 7. Macrophage infiltration into the clot can be observed at Day 14. The aneurysm model starts to shrink from Day 28, and hyperplasia tissue begins to present. The dimension of the model stabilizes from Day 56 onwards, while the model cavity is mostly occupied by hyperplasia tissue. The immunology results indicate the presence of myofibroblasts at this stage. In conclusion, a mechanism describing tissue remodeling of aneurysm model with endovascular thrombus is proposed. In the model, the thrombosis is explained by coagulation under hypoxia (low oxygen level) condition, and the later change from thrombus to hyperplasia is closely related to wound healing process. The healing of aneurysm is led by macrophage infiltration and the fibroplasia is the major tissue remodeling activity. Fibroblasts are later binded with actin fibers to from myofibroblasts which are responsible for aneurysm contraction. As a result of healing process, the aneurysm model gradually attains a stable stage.
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