The purpose of this project is to define hemostatic regulatory mechanisms of the brain. Because thrombo-occlusive processes are so important for stroke pathophysiology, brain regulation of hemostasis is a critical issue. Our data suggest that astrocyte- endothelial interactions at the blood-brain barrier provide a unique hemostatic regulatory system for the brain; moreover, this brain- specific regulatory system appears to have effects that are largely procoagulant. We will further define these astrocyte-endothelial interactions by analysis of hemostatic function of bovine brain capillary endothelial cells grown in monolayers and capillary-like structures. We will determine the hemostatic effects of diffusible factors elaborate by astrocytes and brain capillary endothelial cells. We will define the role of trnsformaing growth factor-beta (TGF-beta) as a mediator of brain hemostasis expression by analyzing TGF-beta synthesis and activation in our cell culture systems. Finally, we will delineate the effects of hypoxic-ischemic injury on brain regulation of hemostasis by exposure of our cell culture systems to severe hypoxia, with and without substrate deprivation, for period of 6-24 hours. Our findings will define pathways of brain regulation of hemostasis and pave the way for pharmacotherapies designed to prevent and treat strike by enhancement of the brain~s endogenous anticoagulant system.
| 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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