Projects and Grants
NIH NINDS RO1 NS050576
PI: Fatima Sehba , M.D.
08/01/2007-04/30/2011
Microvascular injury after subarachnoid hemorrhage
This grant investigates the effect of structural injury in microvessels on their function and with the focus on intraluminal platelet aggregation in initiating these events after subarachnoid hemorrhage (SAH). We have documented early structural injury in cerebral microvessels after SAH that could affect their function and contribute to acute ischemia. In an experimental model of SAH we have found intraluminal platelet aggregation, degradation of collagen IV, the major protein of basal lamina, and activation of vascular collagenases within hours after SAH. In this proposal SAH will be induced in the rat by endovascular perforation. Cerebral blood flow, blood pressure and intracranial pressure will be continuously recorded. Cerebral microvessels (?100um) will be examined for perfusion, blood-brain barrier function, platelet aggregation, endothelial injury, matrix metalloproteinase-9 activation, and collagen IV loss during the first 48 hours after SAH. The effect of early pharmacological inhibition of platelet aggregation on microvascular perfusion and structural changes will be investigated. This study will extend our current understanding of early microvascular injury after SAH, and will evaluate the therapeutic potential of post-hemorrhage blockade of platelet aggregation.
PI: Fatima Sehba , M.D.
08/01/2007-04/30/2011
Microvascular injury after subarachnoid hemorrhage
This grant investigates the effect of structural injury in microvessels on their function and with the focus on intraluminal platelet aggregation in initiating these events after subarachnoid hemorrhage (SAH). We have documented early structural injury in cerebral microvessels after SAH that could affect their function and contribute to acute ischemia. In an experimental model of SAH we have found intraluminal platelet aggregation, degradation of collagen IV, the major protein of basal lamina, and activation of vascular collagenases within hours after SAH. In this proposal SAH will be induced in the rat by endovascular perforation. Cerebral blood flow, blood pressure and intracranial pressure will be continuously recorded. Cerebral microvessels (?100um) will be examined for perfusion, blood-brain barrier function, platelet aggregation, endothelial injury, matrix metalloproteinase-9 activation, and collagen IV loss during the first 48 hours after SAH. The effect of early pharmacological inhibition of platelet aggregation on microvascular perfusion and structural changes will be investigated. This study will extend our current understanding of early microvascular injury after SAH, and will evaluate the therapeutic potential of post-hemorrhage blockade of platelet aggregation.