The long-term goal of this project is to fully define the role of hemorheology in the pathogenesis of cerebral ischemia. We wish to investigate patients with subarachnoid hemorrhage in order to define hemorheological abnormalities related to cerebral ischemia. We also wish to determine the relationship between hemorheology, thrombosis, and ischemic symptoms with respect to carotid artery atherosclerotic plaques. We will investigate approximately 150 patients with subarachnoid hemorrhage over a period of five years. Hemorheological factors will be determined during their preoperative period and following discharge. Hemorheological determinations will include viscosity (whole blood, RBC-plasma suspension, and plasma) by cone-plate and couette viscometer; red cell aggregation measured by zeta sedimentation ratio and aggregation index; and red cell deformability using a new computerized filtration device. These hemorheological factors will be evaluated in the following contexts: 1) Clinical, as determined by repeated neurological evaluations; 2) Arteriographic, as determined by the presence of vasospasm; 3) Hydrocephalus, as determined by CT scan; 4) Platelete activation and other elements of the coagulation system, as determined by measurements of plasma beta-thromboglobulin, along with fibrinopeptides A and B, plasminogen, alpha 2- antiplasmin, and tissue plasminogen activator inhibitor; 5) Blood volume status, as measured by the chromium-51 method; and 6) Deep vein thrombosis, as determined clinically and by I-125 fibrinogen scans of the extremities. We will analyze approximately 350 carotid endarterectomy specimens over a five year period. The relationship between hemorheology factors and thrombotic activity on the carotid plaque surface will be evaluated using immunoperoxidase stains for fibrin and for beta-thromboglobulin. Regions of plaques subjected to high-and low-shear stress will be identified by pathologic and arteriographic analysis. The immunohistologic characteristics of carotid artery atherosclerotic plaques will be examined in the context of these rheologic features. In addition, pathological features of the carotid plaques will be analyzed with respect to abnormalities of clinical hemorheology (e.g., viscosity and red cell aggregation) and coagulation. Finally, we will examine the relationship between these hemorheological and pathologic features and the presence of ischemic symptoms related to carotid artery disease.
| Fisher, Mark; Kapur, Kevin; Soo, Sylvia et al. (2018) Disseminated Microinfarctions with Cerebral Microbleeds. J Stroke Cerebrovasc Dis 27:e95-e97 |
| Sumbria, Rachita K; Grigoryan, Mher Mahoney; Vasilevko, Vitaly et al. (2018) Aging exacerbates development of cerebral microbleeds in a mouse model. J Neuroinflammation 15:69 |
| Chang, Rudy; Castillo, Juan; Zambon, Alexander C et al. (2018) Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds. Front Cell Neurosci 12:279 |
| Sumbria, Rachita K; Vasilevko, Vitaly; Grigoryan, Mher Mahoney et al. (2017) Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages. J Neuroinflammation 14:114 |
| Hainsworth, Atticus H; Fisher, Mark J (2017) A dysfunctional blood-brain barrier and cerebral small vessel disease. Neurology 88:420-421 |
| Sumbria, Rachita K; Grigoryan, Mher Mahoney; Vasilevko, Vitaly et al. (2016) A murine model of inflammation-induced cerebral microbleeds. J Neuroinflammation 13:218 |
| Fisher, Mark; Moores, Lisa; Alsharif, Mohamad N et al. (2016) Definition and Implications of the Preventable Stroke. JAMA Neurol 73:186-9 |
| Chen, Xiang-Yan; Fisher, Mark (2016) Pathological Characteristics. Front Neurol Neurosci 40:21-33 |
| Fisher, Mark (2016) Cerebral Microbleeds and Thrombolysis: Clinical Consequences and Mechanistic Implications. JAMA Neurol 73:632-5 |
| Lo, Patrick; Crouzet, Christian; Vasilevko, Vitaly et al. (2016) Corrigendum to ""Visualization of microbleeds with optical histology in mouse model of cerebral amyloid angiopathy"" [105, May 2016, 109-113]. Microvasc Res 106:137 |
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