We evaluated by immunocytochemistry cellular localization and time-dependent expression of tumor necrosis factor a (TNF-alpha) and its receptors p55 (TNF-RI) and p75 (TNF-R2) in human ischemic brains. We observed them in microglia, neurons, astrocytes, macrophages and blood vessels. Since TNF-alpha expression was very intense and prolonged in microglia, it probably constitutes the main cellular source of the cytokine following cerebral ischemia in humans. Constitutive expression of TNF-alpha receptors was observed in neurons and blood vessels while in other cells it was induced by ischemia. In macrophages, dominant immunolabeling for TNF-R2 was seen. In other cells, immunoreactions for both types of TNF-alpha receptors were similar but the pattern of immunostaining was different: homogenous for TNF-R1 and granular for TNF-R2. Beneficial and detrimental role of TNF-alpha in cerebral ischemia and supposed mechanisms of action are discussed.
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