Brain edema plays an important role in the secondary brain injury following intracerebral hemorrhage (ICH). It is the long-term goal of our laboratory to identify the mechanisms involved in brain edema formation after ICH. Previous studies indicate that edema formation following ICH may involve several phages. These include a very early phase (first several hours) involving hydrostatic pressure, clot retraction, and transient ischemia around the clot, a second phase (first day) involving the clotting cascade and thrombin production and a third phase (about day 3 in the rat) involving erythrocyte lysis and hemoglobin-induced toxicity. Because of the delay in onset, this third phase may be more amenable to therapeutic intervention by either altering erythrocyte lysis or limiting hemoglobin- induced toxicity. This proposal has three specific aims concerning this third phase: (1) To determine whether erythrocyte lysis and hemoglobin release cause delayed brain edema formation following intracerebral hemorrhage by reducing blood flow, increasing blood-brain barrier permeability or by direct cytotoxicity. (2) To examine the role of hemoglobin breakdown products in ICH- induced brain edema by blocking or inducing heme oxygenase and by elucidating the effects of direct intracerebral infusion of hemoglobin breakdown products. (3) To determine whether complement system activation is involved in erythrocyte lysis in the hematoma following ICH and to examine whether activation of this system also exacerbates brain damage by direct neuronal effects or by inducing neutrophil migration into brain. Intracerebral hemorrhage (ICH) is a common and often fatal subtype of stroke which accounts for about 15% of stroke deaths (20,000/year). Although death may occur acutely after an ICH, in many cases there is a delayed neurological deterioration and death. These experiments are designed to explore these latter events and develop new therapeutic strategies to counter such deterioration.
Showing the most recent 10 out of 124 publications
