Rhubarb attenuates blood-brain barrier disruption via increased zonula occludens-1 expression in a rat model of intracerebral hemorrhage

Wang,Yang; Peng,Fan; Xie,Gui; Chen,Ze‑Qi; Li,Hai‑Gang; Tang,Tao; Luo,Jie‑Kun

doi:10.3892/etm.2016.3330

Rhubarb attenuates blood-brain barrier disruption via increased zonula occludens-1 expression in a rat model of intracerebral hemorrhage

Authors:
- Yang Wang
- Fan Peng
- Gui Xie
- Ze‑Qi Chen
- Hai‑Gang Li
- Tao Tang
- Jie‑Kun Luo
View Affiliations

Affiliations: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: May 11, 2016 https://doi.org/10.3892/etm.2016.3330
Pages: 250-256
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Blood-brain barrier (BBB) disruption is a key pathophysiological factor of intracerebral hemorrhage (ICH). The level of zonula occludens-1 (ZO‑1) has been closely associated with the degree of BBB damage, and is an indicator of BBB destruction. The aim of the present study was to evaluate the effects of rhubarb on BBB function in a rat model of ICH. ICH was induced in rats by treatment with type VII collagenase. Sham‑operated rats were administered with an equal volume of saline. Following the administration of rhubarb decoction (20 g/kg), neurobehavioral function evaluation and Evans blue extravasation assays were performed at days 1, 3 and 5 after ICH. ZO‑1 expression in the brain of ICH‑induced rats were analyzed via reverse transcription‑polymerase chain reaction (RT‑PCR) and immunohistochemical analyses. The results suggested that rhubarb significantly ameliorated neurological symptoms and attenuated BBB permeability. The results of immunohistochemistry and RT‑PCR studies indicated that the expression of ZO‑1 expression was robust in the sham‑operated group and was weak in the vehicle‑treated group at day 3. The present data indicated that rhubarb effectively attenuated ICH‑induced BBB damage in rats, raising the possibility that rhubarb or its active components may be considered useful as neuroprotective drugs for ICH. The protective mechanisms appeared to involve the preservation of BBB integrity and elevation of ZO‑1 protein expression levels.

View Figures

View References

1	Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, et al: Heart disease and stroke statistics-2014 update: A report from the American heart association. Circulation. 129:e28–e292. 2014. View Article : Google Scholar : PubMed/NCBI
2	Rincon F and Mayer SA: The epidemiology of intracerebral hemorrhage in the United States from 1979 to 2008. Neurocrit Care. 19:95–102. 2013. View Article : Google Scholar : PubMed/NCBI
3	Tsai CF, Thomas B and Sudlow CL: Epidemiology of stroke and its subtypes in Chinese vs white populations A systematic review. Neurology. 81:264–272. 2013. View Article : Google Scholar : PubMed/NCBI
4	Wei JW, Huang Y, Wang JG, Liu M, Wong LK, Huang Q, Wu L, Heeley EL, Arima H and Anderson CS: ChinaQUEST Investigators: Current management of intracerebral haemorrhage in China: A national, multi-centre, hospital register study. BMC Neurol. 11:162011.PubMed/NCBI
5	Lu X, Chen-Roetling J and Regan RF: Systemic hemin therapy attenuates blood-brain barrier disruption after intracerebral hemorrhage. Neurobiol Dis. 70:245–251. 2014. View Article : Google Scholar : PubMed/NCBI
6	Zhou QB, Jin YL, Jia Q, Zhang Y, Li LY, Liu P and Liu YT: Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage. Inflammation. 37:107–115. 2014. View Article : Google Scholar : PubMed/NCBI
7	Zazulia AR, Diringer MN, Derdeyn CP and Powers WJ: Progression of mass effect after intracerebral hemorrhage. Stroke. 30:1167–1173. 1999. View Article : Google Scholar : PubMed/NCBI
8	Balami JS and Buchan AM: Complications of intracerebral haemorrhage. Lancet Neurol. 11:101–118. 2012. View Article : Google Scholar : PubMed/NCBI
9	Abbott NJ, Patabendige AA, Dolman DE, Yusof SR and Begley DJ: Structure and function of the blood-brain barrier. Neurobiol Dis. 37:13–25. 2010. View Article : Google Scholar : PubMed/NCBI
10	Yang Y and Rosenberg GA: Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke. 42:3323–3328. 2011. View Article : Google Scholar : PubMed/NCBI
11	Krafft PR, Caner B, Klebe D, Rolland WB, Tang J and Zhang JH: PHA-543613 preserves blood-brain barrier integrity after intracerebral hemorrhage in mice. Stroke. 44:1743–1747. 2013. View Article : Google Scholar : PubMed/NCBI
12	Rosenberg GA: Neurological diseases in relation to the blood-brain barrier. J Cereb Blood Flow Metab. 32:1139–1151. 2012. View Article : Google Scholar : PubMed/NCBI
13	Qiu LB, Zhou Y, Wang Q, Yang LL, Liu HQ, Xu SL, Qi YH, Ding GR and Guo GZ: Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats. Toxicology. 285:31–38. 2011. View Article : Google Scholar : PubMed/NCBI
14	Petty MA and Wettstein JG: Elements of cerebral microvascular ischaemia. Brain Res Brain Res Rev. 36:23–34. 2001. View Article : Google Scholar : PubMed/NCBI
15	Sun H, Tang Y, Guan X, Li L and Wang D: Effects of selective hypothermia on blood-brain barrier integrity and tight junction protein expression levels after intracerebral hemorrhage in rats. Biol Chem. 394:1317–1324. 2013. View Article : Google Scholar : PubMed/NCBI
16	Zahuranec DB, Lisabeth LD, Sánchez BN, Smith MA, Brown DL, Garcia NM, Skolarus LE, Meurer WJ, Burke JF, Adelman EE and Morgenstern LB: Intracerebral hemorrhage mortality is not changing despite declining incidence. Neurology. 82:2180–2186. 2014. View Article : Google Scholar : PubMed/NCBI
17	van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A and Klijn CJ: Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: A systematic review and meta-analysis. Lancet Neurol. 9:167–176. 2010. View Article : Google Scholar : PubMed/NCBI
18	Gao L, Zhao H, Liu Q, Song J, Xu C, Liu P, Gong W, Wang R, Liu KJ and Luo Y: Improvement of hematoma absorption and neurological function in patients with acute intracerebral hemorrhage treated with Xueshuantong. J Neurol Sci. 323:236–240. 2012. View Article : Google Scholar : PubMed/NCBI
19	Wang Y, Huang X, Liang QH, Fan R, Qin F, Guo Y, Yan KP, Liu W, Luo JK, Li YH, et al: A strategy for detecting absorbed bioactive compounds for quality control in the water extract of rhubarb by ultra performance liquid chromatography with photodiode array detector. Chin J Integr Med. 18:690–698. 2012. View Article : Google Scholar : PubMed/NCBI
20	Gu J, Zhang X, Fei Z, Wen A, Qin S, Yi S, Chen Y and Li X: Rhubarb extracts in treating complications of severe cerebral injury. Chin Med J (Engl). 113:529–531. 2000.(In Chinese). PubMed/NCBI
21	Collins RA: A ten-year audit of traditional Chinese medicine and other natural product research published in the Chinese Medical Journal (2000–2009). Chin Med J (Engl). 124:1401–1408. 2011.PubMed/NCBI
22	Pharmacopoeia Commission: Pharmacopoeia of the People's Republic of China 2010 (9th). Chemical Industry Press. Beijing: 222010.
23	Wei SY, Yao WX, Ji WY, Wei JQ and Peng SQ: Qualitative and quantitative analysis of anthraquinones in rhubarbs by high performance liquid chromatography with diode array detector and mass spectrometry. Food Chem. 141:1710–1715. 2013. View Article : Google Scholar : PubMed/NCBI
24	Tang YP, Cai DF and Liu J: Research on acting mechanism of rhubarb on aquaporin-4 in rats with blood-brain barrier injury after acute cerebral hemorrhage. Zhong Guo Zhong Xi Yi Jie He Za Zhi. 26:152–156. 2006.(In Chinese).
25	Yong-Jun F, Yi Z, Zun-Hua K, Zhen-Guo Z, Feng Z and Lu-Ning B: Effects of rhubarb powder on serum complement 3, complement 4, and hs-CRP in patients with intracerebral hemorrhage. Zhong Guo Zhong Xi Yi Jie He Za Zhi. 33:168–171. 2013.(In Chinese).
26	Zhou X, Wang L, Wang M, Xu L, Yu L, Fang T and Wu M: Emodin-induced microglial apoptosis is associated with TRB3 induction. Immunopharmacol Immunotoxicol. 33:594–602. 2011. View Article : Google Scholar : PubMed/NCBI
27	Wang YS and Chen FQ: The influence of ten decoction methods on active components in rhubarb decoction. Zhong Cheng Yao. 12:5–7. 1990.(In Chinese).
28	Rosenberg GA, Mun-Bryce S, Wesley M and Kornfeld M: Collagenase induced intracerebral hemorrhage in rats. Stroke. 21:801–807. 1990. View Article : Google Scholar : PubMed/NCBI
29	Park HK, Lee SH, Chu K and Roh JK: Effects of celecoxib on volumes of hematoma and edema in patients with primary intracerebral hemorrhage. J Neurol Sci. 279:43–46. 2009. View Article : Google Scholar : PubMed/NCBI
30	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
31	Bangsow T, Baumann E, Bangsow C, Jaeger MH, Pelzer B, Gruhn P, Wolf S, von Melchner H and Stanimirovic DB: The epithelial membrane protein 1 is a novel tight junction protein of the blood-brain barrier. J Cereb Blood Flow Metab. 28:1249–1260. 2008. View Article : Google Scholar : PubMed/NCBI
32	Keep RF, Zhou N, Xiang J, Andjelkovic AV, Hua Y and Xi G: Vascular disruption and blood-brain barrier dysfunction in intracerebral hemorrhage. Fluids Barriers CNS. 11:182014. View Article : Google Scholar : PubMed/NCBI
33	Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, Spilker J, Duldner J and Khoury J: Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke. 28:1–5. 1997. View Article : Google Scholar : PubMed/NCBI
34	Pardridge WM: Targeting neurotherapeutic agents through the blood-brain barrier. Arch Neurol. 59:35–40. 2002. View Article : Google Scholar : PubMed/NCBI
35	Liebner S, Czupalla CJ and Wolburg H: Current concepts of blood-brain barrier development. Int J Dev Biol. 55:467–476. 2011. View Article : Google Scholar : PubMed/NCBI
36	Nusrat A, Parkos CA, Verkade P, Foley CS, Liang TW, Innis-Whitehouse W, Eastburn KK and Madara JL: Tight junctions are membrane microdomains. J Cell Sci. 113:1771–1781. 2000.PubMed/NCBI
37	Fischer S, Wobben M, Marti HH, Renz D and Schaper W: Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1. Microvasc Res. 63:70–80. 2002. View Article : Google Scholar : PubMed/NCBI