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Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

The ameliorative effect of bloodletting puncture at hand twelve Jing-well points on cerebral edema induced by permanent middle cerebral ischemia via protecting the tight junctions of the blood-brain barrier

Authors: Nannan Yu, Zhenguo Wang, Yucen Chen, Juntao Yang, Xuan Lu, Yi Guo, Zelin Chen, Zhifang Xu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Cerebral edema, erupting simultaneously with severe ischemic stroke, might lead to increased intracranial pressure, cerebral herniation, and ultimately death. Studies conducted previously by our team have demonstrated the fact that bloodletting puncture at hand twelve Jing-well points (HTWP) could alleviate cerebral edema, which mainly results from the disruption of blood-brain barrier (BBB). The study, therefore, was first designed to demonstrate whether BBB-protection serves an important role in the edema-relief effect of HTWP bloodletting, based on which to research the molecular mechanism underlying.

Methods

The rats were made into model suffering from permanent middle cerebral artery occlusion (pMCAO) and then bloodletting puncture were treated at HTWP once a day. Wet and dry weight method was adopted to evaluate the degree of brain edema, evans blue extravasation and electron microscopy were used to evaluate the integrity of the BBB, and RT-qPCR was carried out to analyze the expression level of occludin, claudin-5, ICAM-1, and VEGF.

Results

Results revealed that bloodletting puncture treatment could reduce water content of brain and the permeability of BBB caused by ischemic stroke. In bloodletting puncture group, ameliorated tight junctions could be observed under electron microscopy. It was demonstrated in further study that, in bloodletting group, compared with pMCAO one, the expression levels of occludin and claudin-5 were up-regulated, while ICAM-1 and VEGF were down-regulated.

Conclusions

In conclusion, bloodletting puncture at HTWP might play a significant role in protecting the tight junctions of BBB, thus alleviating cerebral edema induced by ischemic stroke. Therefore, the therapy of bloodletting puncture at HTWP may be a promising strategy for acute ischemic stroke in the future.
Literature
1.
go back to reference Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322.CrossRefPubMed Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322.CrossRefPubMed
2.
go back to reference Jin R, Yang G, Li G. Molecular insights and therapeutic targets for blood-brain barrier disruption in ischemic stroke: critical role of matrix metalloproteinases and tissue-type plasminogen activator. Neurobiol Dis. 2010;38(3):376–85.CrossRefPubMedPubMedCentral Jin R, Yang G, Li G. Molecular insights and therapeutic targets for blood-brain barrier disruption in ischemic stroke: critical role of matrix metalloproteinases and tissue-type plasminogen activator. Neurobiol Dis. 2010;38(3):376–85.CrossRefPubMedPubMedCentral
3.
go back to reference Perez de la Ossa N, Davalos A. Neuroprotection in cerebral infarction: the opportunity of new studies. Cerebrovascular Dis. 2007;24(Suppl 1):153–6.CrossRef Perez de la Ossa N, Davalos A. Neuroprotection in cerebral infarction: the opportunity of new studies. Cerebrovascular Dis. 2007;24(Suppl 1):153–6.CrossRef
4.
go back to reference Toni D, Fiorelli M, Gentile M, Bastianello S, Sacchetti ML, Argentino C, Pozzilli C, Fieschi C. Progressing neurological deficit secondary to acute ischemic stroke. A study on predictability, pathogenesis, and prognosis. Arch Neurol. 1995;52(7):670–5.CrossRefPubMed Toni D, Fiorelli M, Gentile M, Bastianello S, Sacchetti ML, Argentino C, Pozzilli C, Fieschi C. Progressing neurological deficit secondary to acute ischemic stroke. A study on predictability, pathogenesis, and prognosis. Arch Neurol. 1995;52(7):670–5.CrossRefPubMed
5.
go back to reference Wang Z, Leng Y, Tsai LK, Leeds P, Chuang DM. Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2011;31(1):52–7.CrossRef Wang Z, Leng Y, Tsai LK, Leeds P, Chuang DM. Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2011;31(1):52–7.CrossRef
6.
go back to reference Spatz M. Past and recent BBB studies with particular emphasis on changes in ischemic brain edema: dedicated to the memory of Dr. Igor Klatzo. Acta Neurochir Suppl. 2010;106:21–7.CrossRefPubMed Spatz M. Past and recent BBB studies with particular emphasis on changes in ischemic brain edema: dedicated to the memory of Dr. Igor Klatzo. Acta Neurochir Suppl. 2010;106:21–7.CrossRefPubMed
7.
go back to reference Ding J, Guo Y. Effects of bloodletting puncture at hand twelve Jing-well points on state of consciousness in the patient of early stroke. Zhongguo Zhenjiu. 2004;24(10):673–6. Ding J, Guo Y. Effects of bloodletting puncture at hand twelve Jing-well points on state of consciousness in the patient of early stroke. Zhongguo Zhenjiu. 2004;24(10):673–6.
8.
go back to reference Guo Y, Wang XY, Xu TP, Dai ZH, Li YC. Clinical observation of the influence of bloodletting puncture at hand twelve Jing-well points on consciousness and heart rate in patients with wind stroke. Tianjin Zhongyiyao. 2003;20(2):35–7. Guo Y, Wang XY, Xu TP, Dai ZH, Li YC. Clinical observation of the influence of bloodletting puncture at hand twelve Jing-well points on consciousness and heart rate in patients with wind stroke. Tianjin Zhongyiyao. 2003;20(2):35–7.
9.
go back to reference Gao L, Chen Z, Tian L, Li Z, Guo Y. Effects of bloodletting puncture at Jing-well points in distal ends of finger and toe on survival rate and brain edema in cerebral ischemic rats. J Tradit Chin Med. 2012;32(3):471–6.CrossRefPubMed Gao L, Chen Z, Tian L, Li Z, Guo Y. Effects of bloodletting puncture at Jing-well points in distal ends of finger and toe on survival rate and brain edema in cerebral ischemic rats. J Tradit Chin Med. 2012;32(3):471–6.CrossRefPubMed
10.
go back to reference Lu X, Chen Z, Guo Y, Gao L, Jiang L, Li Z, Fang J. Blood-letting punctures at twelve Jing-well points of the hand can treat cerebral ischemia in a similar manner to mannitol. Neural Regen Res. 2013;8(6):532–9.PubMedPubMedCentral Lu X, Chen Z, Guo Y, Gao L, Jiang L, Li Z, Fang J. Blood-letting punctures at twelve Jing-well points of the hand can treat cerebral ischemia in a similar manner to mannitol. Neural Regen Res. 2013;8(6):532–9.PubMedPubMedCentral
11.
go back to reference Prakash R, Carmichael ST. Blood-brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury. Curr Opin Neurol. 2015;28(6):556–64.CrossRefPubMedPubMedCentral Prakash R, Carmichael ST. Blood-brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury. Curr Opin Neurol. 2015;28(6):556–64.CrossRefPubMedPubMedCentral
12.
go back to reference Tu Y, Miao XM, Yi TL, Chen XY, Sun HT, Cheng SX, Zhang S. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury. Neural Regen Res. 2016;11(6):931–6.PubMedPubMedCentral Tu Y, Miao XM, Yi TL, Chen XY, Sun HT, Cheng SX, Zhang S. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury. Neural Regen Res. 2016;11(6):931–6.PubMedPubMedCentral
13.
go back to reference Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84–91.CrossRefPubMed Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84–91.CrossRefPubMed
14.
go back to reference Li SY, Yang D, Fu ZJ, Woo T, Wong D, Lo AC. Lutein enhances survival and reduces neuronal damage in a mouse model of ischemic stroke. Neurobiol Dis. 2012;45(1):624–32.CrossRefPubMed Li SY, Yang D, Fu ZJ, Woo T, Wong D, Lo AC. Lutein enhances survival and reduces neuronal damage in a mouse model of ischemic stroke. Neurobiol Dis. 2012;45(1):624–32.CrossRefPubMed
15.
go back to reference Kimelberg HK. Current concepts of brain edema. Review of laboratory investigations. J Neurosurg. 1995;83(6):1051–9.CrossRefPubMed Kimelberg HK. Current concepts of brain edema. Review of laboratory investigations. J Neurosurg. 1995;83(6):1051–9.CrossRefPubMed
16.
go back to reference He SQ, Guo Y, Ma YF, Miao WF, Wang XY. Experimental study about the influence of bloodletting puncture at hand twelve Jing-well points on H+ concentration of ischemic brain tissue in rats with experimental cerebral ischemia. Zhenjiu Lin Chuang Za Zhi. 2002;18(2):43–4. He SQ, Guo Y, Ma YF, Miao WF, Wang XY. Experimental study about the influence of bloodletting puncture at hand twelve Jing-well points on H+ concentration of ischemic brain tissue in rats with experimental cerebral ischemia. Zhenjiu Lin Chuang Za Zhi. 2002;18(2):43–4.
17.
go back to reference Guo Y, Hu LM, Zhang YJ, Wang XY, Miao WF, Xu TP. Dynamic observation of the influence of bloodletting puncture of hand twelve Jing-well points on extracellular calcium ion concentration in rats with experimental cerebral ischemia. Zhenjiu Linchuang Zazhi. 1999;15(6):48–50. Guo Y, Hu LM, Zhang YJ, Wang XY, Miao WF, Xu TP. Dynamic observation of the influence of bloodletting puncture of hand twelve Jing-well points on extracellular calcium ion concentration in rats with experimental cerebral ischemia. Zhenjiu Linchuang Zazhi. 1999;15(6):48–50.
18.
go back to reference Ma YF, Guo Y, Zhang YJ, Xu TP, Bao JZ. Dynamic observation about the influence of bloodletting puncture at hand twelve Jing-well points on K+, Na+ concentration of ischemic brain tissue in rats with experimental cerebral ischemia. Zhongguo Zhenjiu. 1997;17(9):562–4. Ma YF, Guo Y, Zhang YJ, Xu TP, Bao JZ. Dynamic observation about the influence of bloodletting puncture at hand twelve Jing-well points on K+, Na+ concentration of ischemic brain tissue in rats with experimental cerebral ischemia. Zhongguo Zhenjiu. 1997;17(9):562–4.
19.
go back to reference Guo Y, Zhang YJ, Wang XY, Xu TP, Ren SS, Ren HZ, Wang X. Effects of bloodletting puncture at hand twelve Jing-well points on the intracranial haemodynamics of stroke patients. Zhenjiu Linchuang Zazhi. 1995;11(6):21–3. Guo Y, Zhang YJ, Wang XY, Xu TP, Ren SS, Ren HZ, Wang X. Effects of bloodletting puncture at hand twelve Jing-well points on the intracranial haemodynamics of stroke patients. Zhenjiu Linchuang Zazhi. 1995;11(6):21–3.
20.
go back to reference Xu TP, Wang ZT. Experimental research on the effects of bloodletting puncture at hand twelve Jing-well points on brain blood flow in rabbits. Hunan Zhongyiyao Daobao. 1995;2(1):39–41. Xu TP, Wang ZT. Experimental research on the effects of bloodletting puncture at hand twelve Jing-well points on brain blood flow in rabbits. Hunan Zhongyiyao Daobao. 1995;2(1):39–41.
21.
go back to reference Zhou GP, Xu TP, Wang ZT. Preliminary study of bloodletting puncture at hand twelve Jing-well points on brain blood flow in rabbits of cerebral ischemia. Tianjin Zhongyi. 1989;5:22–4. Zhou GP, Xu TP, Wang ZT. Preliminary study of bloodletting puncture at hand twelve Jing-well points on brain blood flow in rabbits of cerebral ischemia. Tianjin Zhongyi. 1989;5:22–4.
22.
go back to reference Zhou GP, Xu TP. Comparison of effects of the twelve Jing points of hands and Quchi (LI 11) bloodletting on rheoencephalogram in rabbits of cerebral ischemia. Zhenci Yanjiu. 1998;4:268–70. Zhou GP, Xu TP. Comparison of effects of the twelve Jing points of hands and Quchi (LI 11) bloodletting on rheoencephalogram in rabbits of cerebral ischemia. Zhenci Yanjiu. 1998;4:268–70.
23.
go back to reference Dewar D, Underhill SM, Goldberg MP. Oligodendrocytes and ischemic brain injury. J Cereb Blood Flow Metab. 2003;23(3):263–74.CrossRefPubMed Dewar D, Underhill SM, Goldberg MP. Oligodendrocytes and ischemic brain injury. J Cereb Blood Flow Metab. 2003;23(3):263–74.CrossRefPubMed
24.
go back to reference Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85.CrossRefPubMed Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85.CrossRefPubMed
25.
26.
go back to reference Gotoh O, Asano T, Koide T, Takakura K. Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin. Stroke. 1985;16(1):101–9.CrossRefPubMed Gotoh O, Asano T, Koide T, Takakura K. Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin. Stroke. 1985;16(1):101–9.CrossRefPubMed
27.
go back to reference Hatashita S, Hoff JT. Brain edema and cerebrovascular permeability during cerebral ischemia in rats. Stroke. 1990;21(4):582–8.CrossRefPubMed Hatashita S, Hoff JT. Brain edema and cerebrovascular permeability during cerebral ischemia in rats. Stroke. 1990;21(4):582–8.CrossRefPubMed
28.
go back to reference Petty MA, Wettstein JG. Elements of cerebral microvascular ischaemia. Brain Res Brain Res Rev. 2001;36(1):23–34.CrossRefPubMed Petty MA, Wettstein JG. Elements of cerebral microvascular ischaemia. Brain Res Brain Res Rev. 2001;36(1):23–34.CrossRefPubMed
29.
go back to reference Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993;123(6 Pt 2):1777–88.CrossRefPubMed Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993;123(6 Pt 2):1777–88.CrossRefPubMed
30.
go back to reference Balda MS, Flores-Maldonado C, Cereijido M, Matter K. Multiple domains of occludin are involved in the regulation of paracellular permeability. J Cell Biochem. 2000;78(1):85–96.CrossRefPubMed Balda MS, Flores-Maldonado C, Cereijido M, Matter K. Multiple domains of occludin are involved in the regulation of paracellular permeability. J Cell Biochem. 2000;78(1):85–96.CrossRefPubMed
31.
go back to reference Huber D, Balda MS, Matter K. Occludin modulates transepithelial migration of neutrophils. J Biol Chem. 2000;275(8):5773–8.CrossRefPubMed Huber D, Balda MS, Matter K. Occludin modulates transepithelial migration of neutrophils. J Biol Chem. 2000;275(8):5773–8.CrossRefPubMed
32.
go back to reference Lacaz-Vieira F, Jaeger MM, Farshori P, Kachar B. Small synthetic peptides homologous to segments of the first external loop of occludin impair tight junction resealing. J Membr Biol. 1999;168(3):289–97.CrossRefPubMed Lacaz-Vieira F, Jaeger MM, Farshori P, Kachar B. Small synthetic peptides homologous to segments of the first external loop of occludin impair tight junction resealing. J Membr Biol. 1999;168(3):289–97.CrossRefPubMed
33.
go back to reference Morita K, Sasaki H, Furuse M, Tsukita S. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol. 1999;147(1):185–94.CrossRefPubMedPubMedCentral Morita K, Sasaki H, Furuse M, Tsukita S. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol. 1999;147(1):185–94.CrossRefPubMedPubMedCentral
34.
go back to reference Liebner S, Fischmann A, Rascher G, Duffner F, Grote EH, Kalbacher H, Wolburg H. Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 2000;100(3):323–31.CrossRefPubMed Liebner S, Fischmann A, Rascher G, Duffner F, Grote EH, Kalbacher H, Wolburg H. Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 2000;100(3):323–31.CrossRefPubMed
35.
go back to reference Liebner S, Kniesel U, Kalbacher H, Wolburg H. Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur J Cell Biol. 2000;79(10):707–17.CrossRefPubMed Liebner S, Kniesel U, Kalbacher H, Wolburg H. Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur J Cell Biol. 2000;79(10):707–17.CrossRefPubMed
36.
go back to reference Lippoldt A, Kniesel U, Liebner S, Kalbacher H, Kirsch T, Wolburg H, Haller H. Structural alterations of tight junctions are associated with loss of polarity in stroke-prone spontaneously hypertensive rat blood-brain barrier endothelial cells. Brain Res. 2000;885(2):251–61.CrossRefPubMed Lippoldt A, Kniesel U, Liebner S, Kalbacher H, Kirsch T, Wolburg H, Haller H. Structural alterations of tight junctions are associated with loss of polarity in stroke-prone spontaneously hypertensive rat blood-brain barrier endothelial cells. Brain Res. 2000;885(2):251–61.CrossRefPubMed
37.
go back to reference Knowland D, Arac A, Sekiguchi KJ, Hsu M, Lutz SE, Perrino J, Steinberg GK, Barres BA, Nimmerjahn A, Agalliu D. Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron. 2014;82(3):603–17.CrossRefPubMedPubMedCentral Knowland D, Arac A, Sekiguchi KJ, Hsu M, Lutz SE, Perrino J, Steinberg GK, Barres BA, Nimmerjahn A, Agalliu D. Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron. 2014;82(3):603–17.CrossRefPubMedPubMedCentral
38.
go back to reference Kovacs Z, Ikezaki K, Samoto K, Inamura T, Fukui M: VEGF and flt. Expression time kinetics in rat brain infarct. Stroke 1996, 27(10):1865–1872; discussion 1872-1863. Kovacs Z, Ikezaki K, Samoto K, Inamura T, Fukui M: VEGF and flt. Expression time kinetics in rat brain infarct. Stroke 1996, 27(10):1865–1872; discussion 1872-1863.
39.
go back to reference Hayashi T, Abe K, Suzuki H, Itoyama Y. Rapid induction of vascular endothelial growth factor gene expression after transient middle cerebral artery occlusion in rats. Stroke. 1997;28(10):2039–44.CrossRefPubMed Hayashi T, Abe K, Suzuki H, Itoyama Y. Rapid induction of vascular endothelial growth factor gene expression after transient middle cerebral artery occlusion in rats. Stroke. 1997;28(10):2039–44.CrossRefPubMed
40.
go back to reference Lennmyr F, Ata KA, Funa K, Olsson Y, Terent A. Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) following permanent and transient occlusion of the middle cerebral artery in the rat. J Neuropathol Exp Neurol. 1998;57(9):874–82.CrossRefPubMed Lennmyr F, Ata KA, Funa K, Olsson Y, Terent A. Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) following permanent and transient occlusion of the middle cerebral artery in the rat. J Neuropathol Exp Neurol. 1998;57(9):874–82.CrossRefPubMed
41.
go back to reference Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146(5):1029–39.PubMedPubMedCentral Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146(5):1029–39.PubMedPubMedCentral
42.
go back to reference Dietrich JB. The adhesion molecule ICAM-1 and its regulation in relation with the blood-brain barrier. J Neuroimmunol. 2002;128(1–2):58–68.CrossRefPubMed Dietrich JB. The adhesion molecule ICAM-1 and its regulation in relation with the blood-brain barrier. J Neuroimmunol. 2002;128(1–2):58–68.CrossRefPubMed
Metadata
Title
The ameliorative effect of bloodletting puncture at hand twelve Jing-well points on cerebral edema induced by permanent middle cerebral ischemia via protecting the tight junctions of the blood-brain barrier
Authors
Nannan Yu
Zhenguo Wang
Yucen Chen
Juntao Yang
Xuan Lu
Yi Guo
Zelin Chen
Zhifang Xu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1979-6

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