Differential cellular expression of tumor necrosis factor-alpha and Type Itumor necrosis factor receptor after transient global forebrain ischemia

We examined the expression of tumor necrosis factor-alpha (TNF-alpha) and t he Type I tumor necrosis factor receptor, (TNFR1), in relation to c-fos, a known regulator gene of immediate cellular responses, after an extended per iod of global ischemia. The number of TNF-alpha mRNA expressing cells peake d in most brain areas after 8 h of reperfusion. Significant increases in TN FR1 mRNA expression were evident in the cortex at 2 and 8 h of reperfusion and after 8 h of reperfusion in the CA3/CA4 region of the hippocampus. Tran sient neuronal c-fos mRNA expression preceded these responses. TNF-alpha im munoreactivity was seen in neurons >>> oligodendrocytes = perivascular cell s = ependymal cells = vessel wall structures. After ischemia/reperfusion, i ncreased TNF-alpha immunoreactivity was evident only in oligodendrocytes. T NFR1 immunoreactivity in sham brains manifested in bundles of cellular fibe rs of variable length and thickness. In post-ischemic brains, immunoreactiv ity in these cellular processes representing mainly astroglial extensions w as suppressed at 2 h but recovered partially by 8 and 24 h of reperfusion. In contradiction, transient ischemia-induced TNFR1 immunoreactivity was obs erved in somas of large cortical neurons, in activated microglia/macrophage s, perivascular and endothelial cells. Taken together, the increase in neuronal TNF-alpha mRNA appeared not to be followed by substantial translation to protein in the cerebral tissue after an extended period of global ischemia. However, there was increased neuron al TNFR1 immunostaining in conjunction with increased immunostaining for TN F-alpha in oligoglial elements, which suggests signaling to neurons by enha nced oligoglial TNF-alpha. (C) 2001 Elsevier Science B.V. All rights reserv ed.