Effect of tumor necrosis factor- α stimulated gene- 6 on early inflammation and blood brain barrier after ischemic stroke

Abstract

Objective To explore the effects of tumor necrosis factor- α stimulated gene- 6 (TSG- 6) on early inflammation and blood brain barrier (BBB) in mice after ischemic stroke (IS). Methods A total of 90 healthy male C57BL/6j mice were randomly divided into sham-operated group (n=30), vehicle group (n=30) and TSG- 6 treatment group (n=30); the middle cerebral artery occlusion models (IS) in the later two groups were established with suture emboli method; 50 μg TSG-6 or PBS was immediately injected into mice via tail vein after IS. Neurological function deficits were assessed by modified neurological severity scale (mNSS) one and three days after IS; infraction volume was examined by triphenyl tetrazolium chloride (TTC) staining, the changes of brain water content were examined by wet and dry weight method, evans blue (EB) extravasation was assessed by means of EB fluorescent quantitation, myeloperoxidase (MPO) activity was tested by ultraviolet specterphotometry, and Western blotting was used to detect the expressions of matrix metalloproteinase-9 (MMP-9), high-mobility group protein box 1 (HMGB1) and toll- like receptor 4 (TLR4) three days after IS. Results Three days after IS, the mNSS scores (5.253 ± 1.712), infraction volume ([26.100 ± 5.640]% ), EB extravasation ([7.233±3.434] μg/g), brain water content ([71.667 ± 6.518]%), MPO activity ([70.383± 17.558] mU/g) and HMGB1, TLR4 and MMP- 9 expressions (0.503±0.230, 0.482±0.159 and 0.611±0.170) in the TSG- 6 treatment group were significantly lower or smaller than those in the vehicle group ([7.923 ±2.138], ([36.883 ± 8.553]%), ([11.867±4.135] μg/g), ([80.467± 7.045]%), ([112.617± 26.782] mU/g), [0.861 ± 0.137], [0.833 ± 0.193] and [0.910 ± 0.156]) three days after IS (P<0.05); the expressions of MMP-9 (0.611±0.170), HMGB1 (0.503±0.230) and TLR4 (0.482±0.159) in mice of TSG- 6 treatment group were significantly down-regulated as compared with those in vehicle group those days after IS (P<0.05). Conclusion TSG- 6 can exert neuroprotective effect by protecting BBB from damage and reducing brain edema by reduction of MMP- 9 after stroke, which is mediated by downregulation of HMGB1 and its receptor TLR4 and the infiltration of neutrophile granulocytes. Key words: Tumor necrosis factor-α stimulated gene-6; Ischemic stroke; Inflammation response; Blood brain barrier