Tumor necrosis factor-alpha increases in the brain after intracerebral hemorrhage and thrombin stimulation.
OBJECTIVE
The goals of this study were 1) to determine the effects of intracerebral hemorrhage (ICH) on brain tumor necrosis factor (TNF)-alpha levels, which are still controversial; 2) to investigate the role of TNF-alpha in ICH-induced brain injury; 3) to examine the effects of thrombin on brain TNF-alpha levels; and 4) to elucidate the role of TNF-alpha in thrombin-induced neuroprotection.


METHODS
Autologous whole blood and thrombin were injected into the right caudate of rats or mice. Brain TNF-alpha was then determined by enzyme-linked immunosorbent assay and immunohistochemistry. Brain edema and neurological deficits were also examined.


RESULTS
Perihematomal TNF-alpha levels increased after ICH. ICH-induced brain edema was less in TNF-alpha knockout mice compared with wild-type mice (P < 0.05). Intracerebral infusion of thrombin also caused an increase in brain TNF-alpha levels. Thrombin preconditioning reduced thrombin-induced brain edema, but this effect was not blocked by a neutralizing TNF-alpha antibody.


CONCLUSIONS
Increase of perihematomal TNF-alpha levels contributes to brain edema formation after ICH. Thrombin may be a major mediator of ICH-induced TNF-alpha production, but thrombin-induced brain tolerance may not be TNF-alpha mediated.
Hua
Ya
Y
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
Wu
Jimin
J
Keep
Richard F
RF
Nakamura
Takehiro
T
Hoff
Julian T
JT
Xi
Guohua
G
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000517:prevention & control; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin