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| Cerebral Angiogenesis in Neurological Injury and Disease |
The Stiver laboratory investigates the role of the vasculature in neurological processes. Specifically we are interested in understanding new blood vessel growth in brain (cerebral angiogenesis) that accompanies many types of neurological injury, including brain tumor formation, head trauma, and stroke. Our current research focuses on the structure and function of new angiogenic vessels induced by vascular endothelial growth factor (VEGF-A). VEGF-A is one of the most potent stimuli for new blood vessel growth and expression is strongly up-regulated in brain during neurological injury and disease. The ultimate goal of these studies is to develop new strategies targeted to angiogenic vessels for treatment of patients with these neurological problems.
For our studies, adenoviruses that elaborate VEGF-A are injected into the brain tissue of mice and rats. Control animals receive viruses that express non-angiogenic proteins. The use of viruses permits expression of these growth factors over a prolonged periods of time and more closely mimics their natural expression in disease. We have carried out extensive studies on the steps and mechanisms by which nascent vessels of the brain give rise to a neo-vasculature through angiogenesis. What is not known is how the structural and functional properties of these angiogenic vessels differ from normal vessels and whether these differences are important to the progression and course of neurological disease and injury.
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| Blood-Brain Barrier Properties of Angiogenic Vessels |
The first objective of our current studies is to understand how the function of angiogenic vessels differs from that of normal brain blood vessels. In particular, we are interested in the blood-brain-barrier and permeability characteristics of angiogenic vessels. For these experiments, animals are inoculated in the brain with virus expressing VEGF-A. At serial time points, tracers and drugs of different size and character are injected into the blood stream and transport across the angiogenic endothelium is measured by various techniques. These studies are important for understanding brain edema that accompanies malignant brain tumor formation, stroke, and head injury.
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| Therapeutic Angiogenesis in Animal Models of Neurological Disease |
| Angiogenesis is an important component of the pathophysiology of stroke and traumatic head injury. The second objective of our laboratory is to study the therapeutic applications of angiogenesis in animal models of neurological disease. |
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Stroke. We have developed animal models of ischemia and are studying whether VEGF-A can ameliorate stroke through either augmented angiogenesis or by acting as a neuronal survival factor. Animals treated with adenoviral VEGF-A are subjected to an ischemic insult and infarct volumes and neuronal survival rates are measured and compared to control animals.
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Traumatic Brain Injury. We have developed animal models of ischemia and are studying whether VEGF-A can ameliorate stroke through either augmented angiogenesis or by acting as a neuronal survival factor. Animals treated with adenoviral VEGF-A are subjected to an ischemic insult and infarct volumes and neuronal survival rates are measured and compared to control animals.
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