Middle cerebral artery occlusion in the rat was used as the ischemia model. Rats were treated with TXL. In the first stage, the best dosage was chosen based on functional assessment and infarct size. In the second stage, rats were randomly divided into 5 groups: sham control (sham), ischemia and reperfusion (IR) 24 h, TXL24h, I/R72h, TXL72h. TXL(1.6 g/kg/day) administration was pre-performed for 3 days in TXL groups, and was post-performed for 24 h (TXL24h group) or 72 h (TXL72h group). Brain edema was measured by water content, MRI and AQP4 expression. Iba1, HMGB1, TLR4, NF-κB expression were examined by immunofluorescence staining or Western blot. TNF-α was determined by enzyme-linked immunosorbent assay.
High dose (1.6 g/kg/day) of TXL remarkably reduced neurological deficit scores and cerebral infarct area. Compared with those results of I/R24h group, pre-post treatment with TXL for 3 days decreased brain water content, down-regulated AQP4 expression, lowered relative signal intensity of T2WI, reduced lesion volume ratio, and inhibited the activation of microglia, HMGB1, TLR4, NF-κB and TNF-α.
These results indicated that the TXL pre-post treatment for 3 days could be an effective therapy for brain ischemia by inhibiting the development of brain edema and post-ischemic inflammation.