Cellular localization of tumor necrosis factor alpha following focal cerebral ischemia in mice

Tumor necrosis factor alpha (TNF alpha) is a pleiotrophic cytokine with diverse proinflammatory actions. Focal cerebral ischemia induces rapid and dramatic increases in TNFa levels within and surrounding the focus of damaged brain both in striatum and cortex. The actions of TNF alpha during cerebral ischemia may be related to the cell types which deliver and/or accept TNF alpha signals. However, the cellular sources of TNF alpha following cerebral ischemia have not been fully elucidated. The present study was designed to determine the cellular localization of TNF alpha following permanent middle cerebral artery occlusion (MCAO) in mice. As judged by immunohistochemistry, TNF alpha expression in the ischemic hemisphere was increased at 3 h following MCAO, peaked at 6 to 12 h, and decreased at 24 h. Double immunostaining for TNF alpha and neuron specific enolase (NSE) or glial fibrillary acidic protein (GFAP) showed that TNF alpha positive neurons were observed in both the ischemic core and perifocal region, while TNF alpha positive astrocytes were observed in the outer cortical layer, the corpus callosum, the molecular layer of fthe hippocampus, and periventricular areas. The presence of TNF alpha immunoreactivity in neurons and nerve fibers following MCAO suggests that TNF alpha expressed in ischemic neurons might be delivered via axonal transport, while TNF alpha immunoreactivity in astrocyte end-feet and ependymal cells following MCAO suggests that TNF alpha may be involved in blood-brain barrier disruption and the initiation of inflammation in the brain. (C) 1998 Elsevier Science B.V. All rights reserved.