Our recent findings of robust neurovascular protection with early blood pressure (BP) lowering after stroke has prompted us to, in this competitive renewal, continue to elucidate mechanisms of the protective effects of BP management in the hours after stroke. Our long term goal is to understand the pathways of neurovascular injury in the brain during and after ischemic stroke in order to design and implement better treatments for stroke patients. In the first funding period, we determined that BP lowering after reperfusion is neurovascularprotective, and the best outcomes are achieved when angiotensin blockade is employed. The central hypothesis for the proposed research is that vascular protection, accomplished by early BP lowering, activates endogenous survival proteins, including those of the antiapoptosis and angiogenic pathways, even without reperfusion. We plan to test our central hypotheses and accomplish the overall objectives of this application through the following specific aims:
Specific Aim #1 : Determine the extent to which recovery after cerebral ischemia and BP lowering is dependent upon the presence and method of reperfusion. Our working hypothesis is that the neurovascular protective effect of early BP lowering persists whether or not reperfusion is achieved, mechanically or by thrombolysis.
Specific Aim #2 : Determine the extent to which early BP lowering after cerebral ischemia induces endogenous survival pathways. Our working hypothesis is that early BP lowering induces a "post conditioning"- like state that results in persistent vascular protection, leading to recovery. This protection is reliant on antiapoptotic Akt and proangiogenic VEGF activation.

Agency
National Institute of Health (NIH)
Type
Non-HHS Research Projects (I01)
Project #
5I01BX000891-04
Application #
8696788
Study Section
Cardiovascular Studies A (CARA)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Charlie Norwood VA Medical Center
Department
Type
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30904