Cellular localization of tumor necrosis factor alpha following focal cerebral ischemia in mice.
Tumor necrosis factor alpha (TNFalpha) is a pleiotrophic cytokine with diverse proinflammatory actions. Focal cerebral ischemia induces rapid and dramatic increases in TNFalpha levels within and surrounding the focus of damaged brain both in striatum and cortex. The actions of TNFalpha during cerebral ischemia may be related to the cell types which deliver and/or accept TNFalpha signals. However, the cellular sources of TNFalpha following cerebral ischemia have not been fully elucidated. The present study was designed to determine the cellular localization of TNFalpha following permanent middle cerebral artery occlusion (MCAO) in mice. As judged by immunohistochemistry, TNFalpha 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 TNFalpha and neuron specific enolase (NSE) or glial fibrillary acidic protein (GFAP) showed that TNFalpha positive neurons were observed in both the ischemic core and perifocal region, while TNFalpha positive astrocytes were observed in the outer cortical layer, the corpus callosum, the molecular layer of the hippocampus, and periventricular areas. The presence of TNFalpha immunoreactivity in neurons and nerve fibers following MCAO suggests that TNFalpha expressed in ischemic neurons might be delivered via axonal transport, while TNFalpha immunoreactivity in astrocyte end-feet and ependymal cells following MCAO suggests that TNFalpha may be involved in blood-brain barrier disruption and the initiation of inflammation in the brain.
Gong
C
C
Department of Neurology, Institute of Neurology, Hua-Shan Hospital Shanghai Medical University, Shanghai 200040, China.
Qin
Z
Z
Betz
A L
AL
Liu
X H
XH
Yang
G Y
GY
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002561:Cerebrovascular Disorders; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D012039:Regional Blood Flow; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D005904:Glial Fibrillary Acidic Protein; D014409:Tumor Necrosis Factor-alpha