CELLULAR-LOCALIZATION OF TUMOR-NECROSIS-FACTOR-ALPHA FOLLOWING FOCAL CEREBRAL-ISCHEMIA IN MICE

Tumor necrosis factor alpha (TNF alpha) is a pleiotrophic cytokine wit h diverse proinflammatory actions. Focal cerebral ischemia induces rap id and dramatic increases in TNFa levels within and surrounding the fo cus of damaged brain both in striatum and cortex. The actions of TNF a lpha during cerebral ischemia may be related to the cell types which d eliver and/or accept TNF alpha signals. However, the cellular sources of TNF alpha following cerebral ischemia have not been fully elucidate d. The present study was designed to determine the cellular localizati on 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, peake d at 6 to 12 h, and decreased at 24 h. Double immunostaining for TNF a lpha and neuron specific enolase (NSE) or glial fibrillary acidic prot ein (GFAP) showed that TNF alpha positive neurons were observed in bot h the ischemic core and perifocal region, while TNF alpha positive ast rocytes 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 immunoreactiv ity in astrocyte end-feet and ependymal cells following MCAO suggests that TNF alpha may be involved in blood-brain barrier disruption and t he initiation of inflammation in the brain. (C) 1998 Elsevier Science B.V. All rights reserved.