The Basic Study On The Expression Of Tumor Necrosis Factor-α,Nuclear Factor-κB And The Treatment Of Glucocorticoids In Haematoma Periperal Tissue After Intracerebral Hemorrhage

BACKGROUND AND PURPOSE: Intranscerebral hemorrhage(ICH) accounts for 20%~30% of all human strokes and is associated with 35%~52% mortality within the first month and more than half of the patients died in 2 days after ICH. Tumor necrosis factor- α (TNF- α ) expression is increased in brain after cerebral ischemia, although little is known about its abundance and role in ICH and less is known about the pathogenic role of TNF- α during intracerebral hemorrhage. ICH causes intense neutrophil and macrophage infiltration into the brain. This is correlated with increased TNF- α expression and increased brain damage. Nuclear factor-κB(NF-κ B) is a kind of important transcription factor, taking part in controling transcription on many target genes including tumor necrosis factor- α (TNF-α) , and TNF- α plays a key role in the inflammatory injury after intranscerebral hemorrhage. To determine the role of TNF- α and NF-κB during ICH and the effect of inhibiting immunoreactivity and inflammation under using dexamethasone, the collagenase/heparin-induced ICH model in rats was used because it is accompanied by a pronounced and well-characterized inflammatory response. This study intended to observe the dynamic expression of tumor necrosis factor- α, nuclear factor-κB in the brain tissue surrounded the hematoma in rats, analyzing the relationship of them with intracerebral hemorrhage.Method: Fifty-six healthy Wister rats weighing 250~320 g were randomly assigned to three groups including (1)ICH group 24 rats; (2) Dexamethasone-treated group 24 rats; (3)Sham controls group 8 rats. Allexperimental rats were anesthetized, and ICH was induced by intrastriatal administration of heparin and collagenase. Samples included brain tissues surrounding the haematoma site at 4hours> 12hours, 48hours> 7days respectivly (6 rats on different time pionts, but 2 rats in sham-operated group), using immunohistochemical SABC staining methods to demonstrate TNF- a and NF- k B in rats brain slice. Sham-operated animals were infused with the same volme of saline. Statistics: Statistics were performed on analysis software SPSS10.0. Values were expressed as mean ±SD (normal distribution). Continuous variables between two groups were compared by using Student t test. For continuous variables, comparisons among groups were analyzed by using one-way ANOVA. Probability values were considered significant at the 0.05 level. Excel 2000 was employed to make diagrams.Results: (1) At 4 hours after ICH, rare small, round cells with minimal cytoplasm, like leukocytes, near the periperal tissue of the hematoma were imrnunoreactive with TNF- a and NF- k B antibodies. Twelve hours after ICH, the TNF- a and NF- k B positive cell bodies surrounding hematoma increased prominently, like characteristic of microglia At 48 hours a population of the TNF- a and NF- k B positive cell bodies were identifiable, which were also strongly immunoreactive. Macrophages and neutrophils infiltrated the surrounding tissue of the hematoma The expression of TNF- a and NF- k B had no significant change at seven days after ICH. Compared with dexamethasone-treated group and sham controls group, the probability values were significant (PO.05) . (2) Dexamethasone-treated group: Compared with ICH group, the TNF- a and NF- k B positive cell bodies surrounding hematoma were less , and still continuned to 7 days (PO.05) . (3) The brain edema in the periperal tissue of hematoma was associated with positive cells of TNF- a and NF- k B, and that of dexamethasone-treated group presented a lower degree than of intranscerebral hemorrhage group.Conclusions: (1) The expression of TNF- a and NF- k B increased in the brain tissue surrounding the hematoma after acute cerebral hemorrhage in rats, at the same time, correlated with inflammatory cells infiltrating into the brain. (2) Treatment with dexamethasone might significantly attenuate the increasing of TNF- a and NF- k B, meanwhile, inhibit the infiltration of inflammatory cells. (3) Treatment with dexamethasone contribute to the alleviation of brain tissue edema surrounding the hematoma after acute cerebral hemorrhage in rats.