Spontaneous intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype. If the patient survives the ictus, the resulting hematoma within brain parenchyma triggers a series of events leading to secondary insults and severe neurological deficits. Although the hematoma in human gradually resolves within several months, restoration of function is graded and usually incomplete. The neurological deficits in ICH patients are permanent and disabling. [unreadable] [unreadable] To understand the underlying mechanisms of ICH-induced brain injury and to evaluate therapeutic interventions a number of animal models of ICH have been developed. A reproducible rat ICH model, involving infusion of autologous blood into the caudate, has been used extensively to study mechanisms of brain injury and, in particular, early edema formation. It has, though, been difficult to find correlates of the long-term effects of human ICH. Recently, however, we have developed behavioral tests that can detect prolonged neurological deficits and we, and others, have found that there is delayed brain atrophy in animal models of ICH. The mechanisms involved in this prolonged and delayed brain injury after ICH are as yet unknown, but our preliminary data suggest a role for iron overload and oxidative stress. We propose to test the following hypotheses: 1) To determine whether iron overload in the brain after red blood cell lysis plays a key role in brain atrophy and prolonged neurological deficits after ICH. 2) To determine whether iron overload aggravates oxidative stress which contributes to delayed neurodegeneration after ICH. [unreadable] [unreadable] The purpose of our project is to investigate the mechanisms of delayed neurodegeneration after ICH. The long-term goal of our studies is to limit hemorrhagic brain injury. If our hypotheses are correct, these experiments may lead to novel therapies for ICH by either limiting iron overload or attenuating oxidative brain injury. [unreadable] [unreadable]