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The protective role of Tongxinluo on blood-brain barrier after ischemia-reperfusion brain injury.
J Ethnopharmacol. 2013 Jul 09; 148(2):632-9.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Tongxinluo (TXL), a renowned traditional Chinese medicine, consists of several different kinds of ingredients and has been widely used to treat myocardial infarction and ischemic stroke. However, the underlying neuroprotective mechanisms are not fully understood.

AIM OF THE STUDY

We focus on the effect of TXL on blood-brain barrier (BBB) including edema formation and tight junction (TJ) protein rearrangement, and inflammatory response after transient middle cerebral artery occlusion (tMCAO). We further explore the protective mechanism of TXL on ischemia-induced BBB damage.

MATERIALS AND METHODS

Adult CD1 male mice (n=168) were randomly divided into TXL pre-treatment group, TXL pre-post treatment group, TXL post-treatment group, control group and sham group. Mice in TXL pre-treatment group were given TXL solution by 1g/kg/day orally for 7 days before tMCAO. Mice in pre-post treatment group were continuously given TXL 7 days before and 14 days after tMCAO. Mice in TXL post-treatment group were given TXL solution immediately after tMCAO. Rotarod test and neurological severity scores were evaluated at 1-14 days following tMCAO. Brains were harvested for examining infarct volume, edema formation, and immunofluorescent staining at 1 and 3 days after tMCAO. Cytokines IL-6, IL-1β and TNF-α mRNA expression, and BBB permeability were further examined by RT-PCR and immunostaining.

RESULTS

TXL pre-post treatment improved neurobehavioral outcomes and reduced infarct volume compared to the control (p<0.05). Meanwhile, hemispheric swelling, Evans blue and IgG protein extravasation reduced, while TJ protein expression up-regulated in pre-post treatment group (p<0.05). Further study indicated that infarct volume was smaller and BBB damage was less severe in TXL pre-post treatment group compared to TXL pre-treatment alone. It was noted that fewer myeloperoxidase (MPO) positive cells and less cytokines IL-6, IL-1β and TNF-α expression in pre-post treatment group compared to the control group (p<0.05).

CONCLUSIONS

TXL pre-treatment and pre-post treatment effectively protected the brain from BBB disruption via alleviating inflammatory response. Moreover, pre-post treatment has better outcomes, suggesting that continuous administration of TXL before and throughout ischemia period is necessary because of multiple functions of TXL.

Authors+Show Affiliations

Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23707212

Citation

Liu, Ye, et al. "The Protective Role of Tongxinluo On Blood-brain Barrier After Ischemia-reperfusion Brain Injury." Journal of Ethnopharmacology, vol. 148, no. 2, 2013, pp. 632-9.
Liu Y, Tang GH, Sun YH, et al. The protective role of Tongxinluo on blood-brain barrier after ischemia-reperfusion brain injury. J Ethnopharmacol. 2013;148(2):632-9.
Liu, Y., Tang, G. H., Sun, Y. H., Lin, X. J., Wei, C., Yang, G. Y., & Liu, J. R. (2013). The protective role of Tongxinluo on blood-brain barrier after ischemia-reperfusion brain injury. Journal of Ethnopharmacology, 148(2), 632-9. https://doi.org/10.1016/j.jep.2013.05.018
Liu Y, et al. The Protective Role of Tongxinluo On Blood-brain Barrier After Ischemia-reperfusion Brain Injury. J Ethnopharmacol. 2013 Jul 9;148(2):632-9. PubMed PMID: 23707212.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The protective role of Tongxinluo on blood-brain barrier after ischemia-reperfusion brain injury. AU - Liu,Ye, AU - Tang,Guang Hui, AU - Sun,Yu Hao, AU - Lin,Xiao Jie, AU - Wei,Cong, AU - Yang,Guo-Yuan, AU - Liu,Jian Rong, Y1 - 2013/05/23/ PY - 2012/12/26/received PY - 2013/05/03/revised PY - 2013/05/14/accepted PY - 2013/5/28/entrez PY - 2013/5/28/pubmed PY - 2014/3/7/medline SP - 632 EP - 9 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 148 IS - 2 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a renowned traditional Chinese medicine, consists of several different kinds of ingredients and has been widely used to treat myocardial infarction and ischemic stroke. However, the underlying neuroprotective mechanisms are not fully understood. AIM OF THE STUDY: We focus on the effect of TXL on blood-brain barrier (BBB) including edema formation and tight junction (TJ) protein rearrangement, and inflammatory response after transient middle cerebral artery occlusion (tMCAO). We further explore the protective mechanism of TXL on ischemia-induced BBB damage. MATERIALS AND METHODS: Adult CD1 male mice (n=168) were randomly divided into TXL pre-treatment group, TXL pre-post treatment group, TXL post-treatment group, control group and sham group. Mice in TXL pre-treatment group were given TXL solution by 1g/kg/day orally for 7 days before tMCAO. Mice in pre-post treatment group were continuously given TXL 7 days before and 14 days after tMCAO. Mice in TXL post-treatment group were given TXL solution immediately after tMCAO. Rotarod test and neurological severity scores were evaluated at 1-14 days following tMCAO. Brains were harvested for examining infarct volume, edema formation, and immunofluorescent staining at 1 and 3 days after tMCAO. Cytokines IL-6, IL-1β and TNF-α mRNA expression, and BBB permeability were further examined by RT-PCR and immunostaining. RESULTS: TXL pre-post treatment improved neurobehavioral outcomes and reduced infarct volume compared to the control (p<0.05). Meanwhile, hemispheric swelling, Evans blue and IgG protein extravasation reduced, while TJ protein expression up-regulated in pre-post treatment group (p<0.05). Further study indicated that infarct volume was smaller and BBB damage was less severe in TXL pre-post treatment group compared to TXL pre-treatment alone. It was noted that fewer myeloperoxidase (MPO) positive cells and less cytokines IL-6, IL-1β and TNF-α expression in pre-post treatment group compared to the control group (p<0.05). CONCLUSIONS: TXL pre-treatment and pre-post treatment effectively protected the brain from BBB disruption via alleviating inflammatory response. Moreover, pre-post treatment has better outcomes, suggesting that continuous administration of TXL before and throughout ischemia period is necessary because of multiple functions of TXL. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/23707212/The_protective_role_of_Tongxinluo_on_blood_brain_barrier_after_ischemia_reperfusion_brain_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(13)00354-1 DB - PRIME DP - Unbound Medicine ER -