Subarachnoid hemorrhage (SAH) is a common subtype of stroke and the mortality rate is high (~35%) in the first several days. The causes of early brain injury following SAH are complicated including brain edema formation, blood-brain barrier disruption, increased intracranial pressure/brief global cerebral ischemia, and neurotoxicity caused by blood components. Research suggests that early brain injury following SAH is a primary therapeutic target. It is well known that the amount of blood released during SAH correlates with neurological deficits and poor clinical outcome. Although hemoglobin has been intensively studied as a potent factor for delayed vasospasm in SAH, the role of hemoglobin and its degradation products (especially iron) in SAH-induced early brain injury is not well studied. Our recent studies have demonstrated: 1) Brain iron overload occurs in a rat model of SAH;2) Deferoxamine, an iron chelator, reduces SAH-induced iron overload, oxidative stress and mortality;3) The complement cascade is activated and membrane attack complex levels are increased in the brain after experimental SAH which may play a role in erythrocyte lysis, iron overload and brain injury. However, major gaps in our knowledge regarding complement activation, erythrocyte lysis, brain iron overload and early brain injury after SAH need to be filled. In this application, therefore, we propose to examine the following Specific Aims: 1) To determine whether deferoxamine attenuates SAH-induced brain edema, blood-brain barrier disruption, hydrocephalus and vasospasm, major factors in SAH outcome;2) To determine whether blocking complement activation reduces erythrocyte lysis, brain iron accumulation and brain injury after SAH. The purpose of our project is to examine mechanisms of early brain injury after SAH. Data from the proposed studies may lead to new therapies for SAH. The long-term goal of our studies is to limit brain damage in SAH patients.
After a brain hemorrhage, lysis of red blood cells causes a build up of iron in the brain. Brain iron accumulation can cause brain cell death and neurological deficits. Our recent studies found that iron chelation reduces brain iron levels and brain cell death in a rat model of subarachnoid hemorrhage. The purpose of this project is to investigate the mechanisms of early brain injury after subarachnoid hemorrhage. The long-term goal of our studies is to limit brain injury after hemorrhagic stroke.
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