Differences in Post-ischemic Motor Recovery and Angiogenesis of MCAO Rats Following Electroacupuncture at Different Acupoints

Author(s): Li Liu, Qun Zhang, Hong-Yu Xie, Wei-Jia Gua, Chun-Rong Bao, Nian-Hong Wang*, Yi Wu*

Journal Name: Current Neurovascular Research

Volume 17 , Issue 1 , 2020

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Abstract:

Background: Electroacupuncture (EA) can promote nerve and vascular regeneration, confer neuroprotection, inhibit apoptosis and inflammatory reactions, reduce oxidative stress injury, regulate neurochemicals and inhibit the formation of brain oedema in cerebral ischemic. However, the precise site of EA stimulation in the treatment of cerebral ischemic is unclear.

Objective: In the present study, we investigated the effect of EA at the acupoints of different meridians in motor function recovery and the involvement of Vascular Endothelial Growth Factor (VEGF), phosphorylated Protein Kinase B (P-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) and Platelet Endothelial Cell Adhesion Molecule-1(CD31) were examined in the peri-infarction cortex of rats.

Methods: The Middle cerebral artery occlusion (MCAO) model or sham surgery was performed in a total of Ninety male Sprague-Dawley rats. Rats were randomly divided into five groups: a sham group, a middle cerebral artery occlusion (MCAO) group, a Yang meridian group, a Yin meridian group and a combined Yang and Yin meridian group. EA stimulus was given during the middle cerebral artery occlusion. The neurobehavioural function was measured using Modified Neurological Severity Scores (mNSS), the rotarod test and the ladder rung walking test, and the protein expression of VEGF, P-Akt, p-eNOS in the peri-infarction cortex was detected by Western blot. Immunofluorescence was used to measure the vascular density of the peri-infarction cortex.

Results: EA at different meridian acupoints has no effect on the infarction volume, while EA at Yin meridian acupoints significantly promoted neurobehavioural functional recovery, increased the vascular density and enhanced protein kinase B/Endothelial nitric oxide synthase (Akt/eNOS) phosphorylation and VEGF expression.

Conclusion: In the early stage of stroke, EA at Yin meridian acupoints can improve neurobehavioural functional recovery and the mechanism of this effect may be related to the enhanced expression of VEGF, P-Akt and p-eNOS in the peri-infarction cortex of rats.

Keywords: Middle cerebral artery occlusion, electroacupuncture, Yang meridian, Yin meridian, angiogenesis, endothelial nitric oxide synthase.

[1]
Yang, G.; Wang, Y.; Zeng, Y. Rapid health transition in China, 1990-2010: Findings from the Global Burden of Disease Study 2010. Lancet, 2013, 381(9882), 1987-2015.
[http://dx.doi.org/10.1016/S0140-6736(13)61097-1] [PMID: 23746901]
[2]
Arai, K.; Jin, G.; Navaratna, D.; Lo, E.H. Brain angiogenesis in developmental and pathological processes: Neurovascular injury and angiogenic recovery after stroke. FEBS J., 2009, 276(17), 4644-4652.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07176.x] [PMID: 19664070]
[3]
Manoonkitiwongsa, P.S.; Jackson-Friedman, C.; McMillan, P.J.; Schultz, R.L.; Lyden, P.D. Angiogenesis after stroke is correlated with increased numbers of macrophages: The clean-up hypothesis. J. Cereb. Blood Flow Metab., 2001, 21(10), 1223-1231.
[http://dx.doi.org/10.1097/00004647-200110000-00011] [PMID: 11598500]
[4]
Zheng, X.W.; Shan, C.S.; Xu, Q.Q. Buyang Huanwu Decoction Targets SIRT1/VEGF pathway to promote angiogenesis after cerebral ischemia/reperfusion injury. Front. Neurosci., 2018, 12, 911.
[http://dx.doi.org/10.3389/fnins.2018.00911] [PMID: 30564092]
[5]
Ma, J.; Luo, Y. Effects of electroacupuncture on expressions of angiogenesis factors and anti-angiogenesis factors in brain of experimental cerebral ischemic rats after reperfusion. J. Tradit. Chin. Med., 2008, 28(3), 217-222.
[http://dx.doi.org/10.1016/S0254-6272(08)60050-3] [PMID: 19004207]
[6]
Patruno, R.; Arpaia, N.; Gadaleta, C.D. VEGF concentration from plasma-activated platelets rich correlates with microvascular density and grading in canine mast cell tumour spontaneous model. J. Cell. Mol. Med., 2009, 13(3), 555-561.
[http://dx.doi.org/10.1111/j.1582-4934.2008.00355.x] [PMID: 18429933]
[7]
Hayashi, T.; Abe, K.; Itoyama, Y. Reduction of ischemic damage by application of vascular endothelial growth factor in rat brain after transient ischemia. J. Cereb. Blood Flow Metab., 1998, 18(8), 887-895.
[http://dx.doi.org/10.1097/00004647-199808000-00009] [PMID: 9701350]
[8]
Xing, Y.; Lai, J.; Liu, X. Netrin-1 restores cell injury and impaired angiogenesis in vascular endothelial cells upon high glucose by PI3K/AKT-eNOS. J. Mol. Endocrinol., 2017, 58(4), 167-177.
[http://dx.doi.org/10.1530/JME-16-0239] [PMID: 28250059]
[9]
Chien, C.T.; Jou, M.J.; Cheng, T.Y.; Yang, C.H.; Yu, T.Y.; Li, P.C. Exendin-4-loaded PLGA microspheres relieve cerebral ischemia/reperfusion injury and neurologic deficits through long-lasting bioactivity-mediated phosphorylated Akt/eNOS signaling in rats. J. Cereb. Blood Flow Metab., 2015, 35(11), 1790-1803.
[http://dx.doi.org/10.1038/jcbfm.2015.126] [PMID: 26058696]
[10]
Zheng, Y.; Wu, Z.; Yi, F. By activating Akt/eNOS Bilobalide B inhibits autophagy and promotes angiogenesis following focal cerebral ischemia reperfusion. Cell. Physiol. Biochem., 2018, 47(2), 604-616.
[http://dx.doi.org/10.1159/000490016] [PMID: 29794436]
[11]
Kim, J.H.; Choi, K.H.; Jang, Y.J. Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice. PLoS One, 2013, 8(2)e56736
[http://dx.doi.org/10.1371/journal.pone.0056736] [PMID: 23418594]
[12]
Kim, Y.R.; Kim, H.N.; Ahn, S.M.; Choi, Y.H.; Shin, H.K.; Choi, B.T. Electroacupuncture promotes post-stroke functional recovery via enhancing endogenous neurogenesis in mouse focal cerebral ischemia. PLoS One, 2014, 9(2)e90000
[http://dx.doi.org/10.1371/journal.pone.0090000] [PMID: 24587178]
[13]
Wu, J.P.; Li, X.Z.; Wang, Y. Effects of electroacupuncture and intracerebral injection of VEGF on Caspase12, Caspase3, and GRP78 genes in rats with cerebral ischemia-reperfusion injury. Sichuan Da Xue Xue Bao Yi Xue Ban, 2019, 50(1), 34-39.https://www.ncbi.nlm.nih.gov/pubmed/31037902
[PMID: 31037902]
[14]
Han, L.; Gao, Y.; Wang, X.; Zhang, Y.; Zhang, X. Mechanism of “Xingnao Kaiqiao” acupuncture for the opening of ATP sensitive potassium channel against cerebral ischemia reperfusion injury in rats. Zhongguo Zhenjiu, 2018, 38(12), 1319-1324.https://www.ncbi.nlm.nih.gov/pubmed/30672221
[PMID: 30672221]
[15]
Wu, C.X.; Feng, Y.H.; Yang, L. Electroacupuncture exerts neuroprotective effects on ischemia/reperfusion injury in JNK knockout mice: the underlying mechanism. Neural Regen. Res., 2018, 13(9), 1594-1601.
[http://dx.doi.org/10.4103/1673-5374.235294] [PMID: 30127120]
[16]
Longa, E.Z.; Weinstein, P.R.; Carlson, S.; Cummins, R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 1989, 20(1), 84-91.
[http://dx.doi.org/10.1161/01.STR.20.1.84] [PMID: 2643202]
[17]
Chen, J.; Sanberg, P.R.; Li, Y. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke, 2001, 32(11), 2682-2688.
[http://dx.doi.org/10.1161/hs1101.098367] [PMID: 11692034]
[18]
Khan, I.S.; Odom, M.; Ehtesham, M. Intraarterial administration of norcantharidin attenuates ischemic stroke damage in rodents when given at the time of reperfusion: Novel uses of endovascular capabilities. J. Neurosurg., 2016, 125(1), 152-159.
[http://dx.doi.org/10.3171/2015.4.JNS142400] [PMID: 26544777]
[19]
Rogers, D.C.; Campbell, C.A.; Stretton, J.L.; Mackay, K.B. Correlation between motor impairment and infarct volume after permanent and transient middle cerebral artery occlusion in the rat. Stroke, 1997, 28(10), 2060-2065.
[http://dx.doi.org/10.1161/01.STR.28.10.2060] [PMID: 9341719]
[20]
Metz, G.A.; Whishaw, I.Q. The ladder rung walking task: A scoring system and its practical application. J. Vis. Exp., 2009;, 12(28): pii: 1204. https://www.ncbi.nlm.nih.gov/pubmed/19525918
[PMID: 19525918]
[21]
Ide, K.; Pott, F.; Van Lieshout, J.J.; Secher, N.H. Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass. Acta Physiol. Scand., 1998, 162(1), 13-20.
[http://dx.doi.org/10.1046/j.1365-201X.1998.0280f.x] [PMID: 9492897]
[22]
Sato, K.; Ogoh, S.; Hirasawa, A.; Oue, A.; Sadamoto, T. The distribution of blood flow in the carotid and vertebral arteries during dynamic exercise in humans. J. Physiol., 2011, 589(Pt 11), 2847-2856.
[http://dx.doi.org/10.1113/jphysiol.2010.204461] [PMID: 21486813]
[23]
Yin, K.J.; Hamblin, M.; Chen, Y.E. Angiogenesis-regulating microRNAs and Ischemic Stroke. Curr. Vasc. Pharmacol., 2015, 13(3), 352-365.
[http://dx.doi.org/10.2174/15701611113119990016] [PMID: 26156265]
[24]
Greenberg, D.A.; Jin, K. From angiogenesis to neuropathology. Nature, 2005, 438(7070), 954-959.
[http://dx.doi.org/10.1038/nature04481] [PMID: 16355213]
[25]
Beck, H.; Plate, K.H. Angiogenesis after cerebral ischemia. Acta Neuropathol., 2009, 117(5), 481-496.
[http://dx.doi.org/10.1007/s00401-009-0483-6] [PMID: 19142647]
[26]
Brouns, R.; De Deyn, P.P. The complexity of neurobiological processes in acute ischemic stroke. Clin. Neurol. Neurosurg., 2009, 111(6), 483-495.
[http://dx.doi.org/10.1016/j.clineuro.2009.04.001] [PMID: 19446389]


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VOLUME: 17
ISSUE: 1
Year: 2020
Page: [71 - 78]
Pages: 8
DOI: 10.2174/1567202617666191223151553
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