of Work: An inflammatory response following acute cerebral ischemia, characterized primarily from animal models and preliminary human studies, has been postulated to contribute to secondary neuronal injury. This response is characterized by the initial release of inflammatory cytokines, particularly tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b), which can stimulate a complex cascade of events resulting in leukocyte migration to the site of injury and enhancement of local coagulation factors. A measurable temporal profile of this inflammatory response has not been well-characterized in humans and may provide an avenue of intervention if it is found to play a significant role in secondary neuronal injury following ischemia. We hypothesize that a measurable inflammatory response, including inflammatory and anti-inflammatory cytokines, leukocyte adhesion molecules, and leukocyte activation is correlated with the severity of brain tissue injury. We also hypothesize that the peaks of these plasma levels correlate temporally with clinical deterioration known to occur in the first 24 to 72 hours following an infarct. Blood samples are drawn from acute stroke patients presenting within 24 hours of their symptom onset and serially for the first 7 days. Serial neurologic exams are performed and MRI scan of the head is done within the first 7 days of admission to determine infarct size. All patients are seen at 90 days after the ischemic event to obtain blood for cytokine levels and to perform neurological outcome scales. Initial analysis of the first 38 patients revealed a significant elevation of Interleukin-6, (IL-6), Interleukin-1 receptor antagonist (IL-1ra) and neopterin at 24 and 72 hours following ischemia as compared to 90-day non-acute levels and age-matched risk factor exposed subjects. TNF-a and IL-1b levels were not measurable at any time points due perhaps to the abundance of secondary soluble antagonists that prevent systemic measurement of a local event. An additional 20 patients have been enrolled and the levels of inflammatory mediators in all samples are being correlated with infarct volume and initial infarct severity. Given the published works 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.
