Tumor Necrosis Factor-α 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)-a levels, which are still controversial; 2) to investigate the role of TNF-a in ICH-induced brain injury; 3) to examine the effects of thrombin on brain TNF-a levels; and 4) to elucidate the role of TNF-a in thrombin-induced neuroprotection. METHODS: Autologous whole blood and thrombin were injected into the right caudate of rats or mice. Brain TNF-a was then determined by enzyme-linked immunosorbent assay and immunohistochemistry. Brain edema and neurological deficits were also examined. RESULTS: Perihematomal TNF-a levels increased after ICH. ICH-induced brain edema was less in TNF-a knockout mice compared with wild-type mice (P < 0.05). Intracerebral infusion of thrombin also caused an increase in brain TNF-a levels. Thrombin preconditioning reduced thrombin-induced brain edema, but this effect was not blocked by a neutralizing TNF-a antibody. CONCLUSION: Increase of perihematomal TNF-a levels contributes to brain edema formation after ICH. Thrombin may be a major mediator of ICH-induced TNF-a production, but thrombin-induced brain tolerance may not be TNF-a mediated.