Induction of tumor necrosis factor-alpha in the mouse hippocampus following transient forebrain ischemia.
To assess the role of tumor necrosis factor-alpha (TNF-alpha) in modulating the process of cerebral ischemic injury, we identified TNF-alpha-producing cells and studied the time course of TNF-alpha expression. Immunoreactivity for TNF-alpha appeared in white matter of the mouse hippocampus as early as 1.5 h following a 30-min global ischemic insult. Double staining for TNF-alpha and glial fibrillary acidic protein (GFAP) suggested that the TNF-alpha-positive cells are most likely microglia, not astrocytes. TNF-alpha immunostaining decreased at 6 and 24 h but increased again at 3 days, when pyramidal neurons showed degeneration. Adjacent-section staining for microglia and double staining with GFAP suggested that TNF-alpha-positive cells in the pyramidal cell layer were microglia and those in the white matter were astrocytes. By 5 days TNF-alpha immunostaining disappeared from these glial cells, while a number of microglia were accumulated in the degenerated hippocampal pyramidal layer. Pyramidal neurons never expressed TNF-alpha immunoreactivity. Western blotting confirmed biphasic TNF-alpha expression. Our findings suggest that early production of TNF-alpha by microglia may activate a cytokine network in post-ischemic brain resulting in TNF-alpha synthesis by astrocytes.
Uno
H
H
Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Matsuyama
T
T
Akita
H
H
Nishimura
H
H
Sugita
M
M
D000818:Animals; D015153:Blotting, Western; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha