Min Cai1, Zhonghai Yu2, Lili Wang3, Xiaoling Song4, Jingsi Zhang5, Zhennian Zhang6, Wen Zhang7, Wenwei Li8, Jun Xiang9, Dingfang Cai10. 1. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: naphel1986@hotmail.com. 2. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: yuzhonghai0715@126.com. 3. Department of Diagnostic Radiology, Xiehe Hospital, Fujian Medical University, Fujian 350001, China. Electronic address: 751501231@qq.com. 4. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: songxl2016@163.com. 5. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: jingsiz@163.com. 6. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: zhennian2000@163.com. 7. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: zw8536899@163.com. 8. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: wenweili2000@aliyun.com. 9. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: chelsea_jx@hotmail.com. 10. Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: dingfangcai@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a widely used traditional Chinese medicine, has been proved multiple therapeutic effects in cerebral ischemic infraction. The purpose of this study was to investigate the protective effects of TXL on the brain edema and post-ischemic inflammatory response. MATERIALS AND METHODS: 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) 24h, TXL24h, I/R72h, TXL72h. TXL(1.6g/kg/day) administration was pre-performed for 3 days in TXL groups, and was post-performed for 24h (TXL24h group) or 72h (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. RESULTS: High dose (1.6g/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. CONCLUSIONS: 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.
ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a widely used traditional Chinese medicine, has been proved multiple therapeutic effects in cerebral ischemic infraction. The purpose of this study was to investigate the protective effects of TXL on the brain edema and post-ischemic inflammatory response. MATERIALS AND METHODS: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) 24h, TXL24h, I/R72h, TXL72h. TXL(1.6g/kg/day) administration was pre-performed for 3 days in TXL groups, and was post-performed for 24h (TXL24h group) or 72h (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. RESULTS: High dose (1.6g/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. CONCLUSIONS: 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.