title: Tumor necrosis factor-alpha increases in the brain after intracerebral hemorrhage and thrombin stimulation.
abstract: 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.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.forename: Jimin
authors.initials: J
authors.lastname: Wu
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Julian T
authors.initials: JT
authors.lastname: Hoff
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
mesh_terms: 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*
chemical_list: D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin