Modeling the Changes of Phospholipidome by Ischemic Stroke in Rat Brain and Plasma
| Autor: | I-Ting Chen, 陳怡婷 |
|---|---|
| Rok vydání: | 2019 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 107 Ischemic stroke is the most commonly encountered cerebrovascular accident. Blockage of a cerebral artery would interrupt the blood and oxygen supply to the affected arterial distributed territory and lead to various extent of parenchymal damage. The release of a plethora of lipid-derived inflammatory mediators precipitates the tissue responses following the circulatory interruption. Hence the phospholipid metabolism conceivably plays a critical role in mediating the pathophysiology of ischemic stroke. Most of matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) studies of ischemic rat brain tissue reported the in situ changes of highly abundant phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), and sphingomyelins (SMs), and associated such changes with histology by MALDI-MS imaging. However, due to various reasons, changes in other classes of phospholipids (PLs) and sphingolipids (SLs) did not receive equal coverage in those studies. Nor were the ischemia-mediated lipid changes in brain parenchyma contrasted to, or compared with the changes in plasma. To address these concerns, the middle cerebral artery of male Sprague-Dawley rats were surgically occluded (permanent middle cerebral artery occlusion; pMCAO). The lipid levels in the ischemic temporal cortex, parietal cortex, striatum, and plasma were analyzed 24hrs after pMCAO using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the presence of internal standards, then contrasted the lipid levels in the respective contralateral non-ischemic regions as well as that in the plasma of sham rats. Other than the conventional statistical analyses, multivariate data analyses were also performed to identify the lipid species that distinguish the ischemic and non-ischemic states. High confidence lipidomic models were established based on these animal studies, while additional validation will further verify the practical utility of these models in the management of cerebral vascular events. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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