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

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