Analysis of Vascular Remodeling in the Circle of Willis after Hemodynamic Insult due to Carotid Occlusion
Tutino, Vincent M.
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Carotid occlusions can be caused by carotid pathologies (stenosis), trauma, or surgical ligation as a defensive treatment option to prevent potential rupture of complex intracranial aneurysms. While they can often lead to stroke and transient ischemic attacks, carotid occlusions, regardless of etiology, have lesser-known repercussions including pathological remodeling of the neurovasculature due to compensatory contralateral flow increase. More and more clinical reports have described de novo intracranial aneurysm formation following carotid occlusion, but this phenomenon is rarely studied and thus not well understood. Past studies at the Toshiba Stroke and Vascular Research Center have focused on the genesis of intracranial aneurysms. Colleagues in my lab have previously induced bilateral carotid artery occlusion in rabbits to drastically increase blood flow through the basilar artery and initiate aneurysm formation at the basilar terminus. In light of increasing reports of de novo aneurysms, the goal of my thesis was to quantitatively investigate the characteristics and extent of flow-induced vascular remodeling in the entire Circle of Willis caused by carotid occlusion in the above-mentioned model. To this end, I utilized vascular corrosion casts of the rabbit Circle of Willis with and without carotid occlusion generated by my colleagues Max Mandelbaum and Liza Pope, and imaged them by scanning electron microscopy. These micrographs enabled me to conduct a detailed quantitative analysis of the gross morphological changes and pathological remodeling induced by carotid occlusion. As a follow-up study, I further asked if flow-induced remodeling could be augmented by two risk factors that are suggested to play a role in intracranial aneurysm etiology: hypertension and estrogen deficiency. In this study, I analyzed corrosion casts of the Circle of Willis from rabbits with unilateral nephrectomy and high salt diet (for hypertension induction), and bilateral oophorectomy (for estrogen deficiency induction) previously prepared by my labmates. I used scanning electron micrographs to quantify pathological changes in the Circle of Willis and compared them to those in the first study. My thesis work provides evidence that flow increase after carotid occlusion in rabbits produces both early compensatory arterial augmentation and progressive pathological remodeling including tortuosity and aneurysm. I have also demonstrated that hypertension and estrogen deficiency increase susceptibility of cerebral vessels to such flow-induced aneurysmal damage and tortuosity throughout the Circle of Willis.