title: Tongxinluo reduces brain edema and inhibits post-ischemic inflammation after middle cerebral artery occlusion in rats.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: naphel1986@hotmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: yuzhonghai0715@126.com.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Diagnostic Radiology, Xiehe Hospital, Fujian Medical University, Fujian 350001, China. Electronic address: 751501231@qq.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: songxl2016@163.com.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: jingsiz@163.com.
authors.forename: Jingsi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: zhennian2000@163.com.
authors.forename: Zhennian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: zw8536899@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: wenweili2000@aliyun.com.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: dingfangcai@163.com.
authors.forename: Dingfang
authors.initials: D
authors.lastname: Cai
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D024243:HMGB1 Protein; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C513941:tongxinluo
keywords: Brain edema; Buthotoxin (PubChem CID: 20054854); Chitin(PubChem CID: 6857375); Ginsenoside Rg1 (PubChem CID: 441923); HMGB1; Hirudin (PubChem CID: 72941487); Inflammation; Isoflavone (PubChem CID: 72304); Jujuboside A (PubChem CID: 171446); MRI; Paeoniflorin (PubChem CID: 442534); Santalol, alpha- and beta- (PubChem CID: 24832101); Tongxinluo; beta-Boswellic acid (PubChem CID: 168928)