Effective management of acute stroke patients has remained limited to the present date. Recent evidence indicates that increased cytokine levels and leukocyte and endothelial cell activation may play a major role in secondary neuronal injury after acute focal cerebral ischemia. The purpose of this investigation is to more clearly characterize the role of the inflammatory response after ischemic injury in humans with regard to its causal influence on secondary neuronal injury and predictive value for long-term functional outcome. Blood samples are drawn from acute stroke patients on admission and serially for the first 7 days. Serial neurologic exams are performed and MRI scan of the head is done within the first 3 days of admission to determine infarct size. Depression scales are done within the first 14 days. All patients are seen at 90 days after the ischemic event for follow-up at which time blood cytokine levels, neurological outcome scales and depression scales are performed. Through analysis of the advent and duration of cytokine activation, we hope to establish a correlative relationship between the postischemic inflammatory response and neuronal injury. Given the published work demonstrating neuronal protection after ischemia in animal models with antagonists of leukocyte activation and of the inflammatory pathways, we expect these results to establish a temporal window for future drug trials in reducing infarct size after acute stroke. A novel approach of correlating sleep architecture in stroke patients with select brainstem and thalamic lesions will be performed by obtaining a polysomnograms in patients 3-6 months after the ischemic event. This may lead to a new understanding of the etiology of sleep disorders in stroke patients and aid in their treatment. We have found a pattern of expression of leukocyte activation and cytokine release reaching a maximum by 72 hours. Studies will continue to further delineate markers on inflammation following ischemia and leukocyte activation via fluorescence-activated cell sorting (FACS) to characterize the role of leukocyte in secondary neuronal injury.
