Journal of Neuroimmune Pharmacology

, Volume 12, Issue 4, pp 575–592 | Cite as

Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia

  • Wen Zhu
  • Yang Ye
  • Yi Liu
  • Xue-Rui Wang
  • Guang-Xia Shi
  • Shuai Zhang
  • Cun-Zhi LiuEmail author


Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.


Cerebral ischemia Acupuncture Neuroprotection Recovery enhancement 



This work was supported by a grant from the National Natural Science Foundation of China (Grant no. 81473501). This work was also supported by the Beijing Nova Program (Grant no. 2014B063).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Adhami F, Liao G, Morozov YM, Schloemer A, Schmithorst VJ, Lorenz JN, Dunn RS, Vorhees CV, Wills-Karp M, Degen JL, Davis RJ, Mizushima N, Rakic P, Dardzinski BJ, Holland SK, Sharp FR, Kuan CY (2006) Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy. Am J Pathol 169:566–583PubMedPubMedCentralCrossRefGoogle Scholar
  2. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963–970PubMedCrossRefGoogle Scholar
  3. Baranano DE, Ferris CD, Snyder SH (2001) Atypical neural messengers. Trends Neurosci 24:99–106PubMedCrossRefGoogle Scholar
  4. Barton GM, Medzhitov R (2003) Toll-like receptor signaling pathways. Science 300:1524–1525PubMedCrossRefGoogle Scholar
  5. Bradbury MW (1985) The blood-brain barrier. Transport across the cerebral endothelium. Circ Res 57:213–222PubMedCrossRefGoogle Scholar
  6. Broughton BR, Reutens DC, Sobey CG (2009) Apoptotic mechanisms after cerebral ischemia. Stroke 40:e331–e339PubMedCrossRefGoogle Scholar
  7. Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Caldwell RW (2003) Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev 19:442–455PubMedCrossRefGoogle Scholar
  8. Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Liou GI, Caldwell RW (2005) Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets 6:511–524PubMedCrossRefGoogle Scholar
  9. Cao CX, Yang QW, Lv FL, Cui J, Fu HB, Wang JZ (2007) Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice. Biochem Biophys Res Commun 353:509–514PubMedCrossRefGoogle Scholar
  10. Ceulemans AG, Zgavc T, Kooijman R, Hachimi-Idrissi S, Sarre S, Michotte Y (2010) The dual role of the neuroinflammatory response after ischemic stroke: modulatory effects of hypothermia. J Neuroinflammation 7:74PubMedPubMedCentralCrossRefGoogle Scholar
  11. Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14PubMedCrossRefGoogle Scholar
  12. Chang J, Zhang H, Tan Z, Xiao J, Li S, Gao Y (2017) Effect of electroacupuncture in patients with post-stroke motor aphasia: neurolinguistic and neuroimaging characteristics. Wien Klin Wochenschr 129(3-4):102–109PubMedCrossRefGoogle Scholar
  13. Chao MV (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 4:299–309PubMedCrossRefGoogle Scholar
  14. Chau AC, Fai Cheung RT, Jiang X, Au-Yeung PK, Li LS (2010) An fMRI study showing the effect of acupuncture in chronic stage stroke patients with aphasia. J Acupunct Meridian Stud 3:53–57PubMedCrossRefGoogle Scholar
  15. Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149PubMedCrossRefGoogle Scholar
  16. Chen A, Lin Z, Lan L, Xie G, Huang J, Lin J, Peng J, Tao J, Chen L (2012) Electroacupuncture at the Quchi and Zusanli acupoints exerts neuroprotective role in cerebral ischemia-reperfusion injured rats via activation of the PI3K/Akt pathway. Int J Mol Med 30:791–796PubMedCrossRefGoogle Scholar
  17. Chen J, Wang J, Huang Y, Lai X, Tang C, Yang J, Wu J, Zeng T, Qu S (2014) Modulatory effect of acupuncture at Waiguan (TE5) on the functional connectivity of the central nervous system of patients with ischemic stroke in the left basal ganglia. PLoS One 9:e96777PubMedPubMedCentralCrossRefGoogle Scholar
  18. Chen B, Tao J, Lin Y, Lin R, Liu W, Chen L (2015) Electro-acupuncture exerts beneficial effects against cerebral ischemia and promotes the proliferation of neural progenitor cells in the cortical peri-infarct area through the Wnt/beta-catenin signaling pathway. Int J Mol Med 36:1215–1222PubMedPubMedCentralCrossRefGoogle Scholar
  19. Cheng YD, Al-Khoury L, Zivin JA (2004) Neuroprotection for ischemic stroke: two decades of success and failure. NeuroRx 1:36–45PubMedPubMedCentralCrossRefGoogle Scholar
  20. Cheng S, Ma M, Ma Y, Wang Z, Xu G, Liu X (2009) Combination therapy with intranasal NGF and electroacupuncture enhanced cell proliferation and survival in rats after stroke. Neurol Res 31:753–758PubMedCrossRefGoogle Scholar
  21. Cheng CY, Lin JG, Su SY, Tang NY, Kao ST, Hsieh CL (2014) Electroacupuncture-like stimulation at Baihui and Dazhui acupoints exerts neuroprotective effects through activation of the brain-derived neurotrophic factor-mediated MEK1/2/ERK1/2/p90RSK/bad signaling pathway in mild transient focal cerebral ischemia in rats. BMC Complement Altern Med 14:92PubMedPubMedCentralCrossRefGoogle Scholar
  22. Cheng CY, Lin JG, Tang NY, Kao ST, Hsieh CL (2015) Electroacupuncture at different frequencies (5Hz and 25Hz) ameliorates cerebral ischemia-reperfusion injury in rats: possible involvement of p38 MAPK-mediated anti-apoptotic signaling pathways. BMC Complement Altern Med 15:241PubMedPubMedCentralCrossRefGoogle Scholar
  23. Choi S, Lee GJ, Chae SJ, Kang SW, Yin CS, Lee SH, Choi SK, Park HK (2010) Potential neuroprotective effects of acupuncture stimulation on diabetes mellitus in a global ischemic rat model. Physiol Meas 31:633–647PubMedCrossRefGoogle Scholar
  24. Chopin V, Lagadec C, Toillon RA, Le Bourhis X (2016) Neurotrophin signaling in cancer stem cells. Cell Mol Life Sci 73(9):1859–1870PubMedCrossRefGoogle Scholar
  25. Chrissobolis S, Faraci FM (2008) The role of oxidative stress and NADPH oxidase in cerebrovascular disease. Trends Mol Med 14:495–502PubMedPubMedCentralCrossRefGoogle Scholar
  26. Chuang CM, Hsieh CL, Li TC, Lin JG (2007) Acupuncture stimulation at Baihui acupoint reduced cerebral infarct and increased dopamine levels in chronic cerebral hypoperfusion and ischemia-reperfusion injured sprague-dawley rats. Am J Chin Med 35:779–791PubMedCrossRefGoogle Scholar
  27. Das KC, Lewis-Molock Y, White CW (1997) Elevation of manganese superoxide dismutase gene expression by thioredoxin. Am J Respir Cell Mol Biol 17:713–726PubMedCrossRefGoogle Scholar
  28. Dong H, Fan YH, Zhang W, Wang Q, Yang QZ, Xiong LZ (2009) Repeated electroacupuncture preconditioning attenuates matrix metalloproteinase-9 expression and activity after focal cerebral ischemia in rats. Neurol Res 31:853–858PubMedCrossRefGoogle Scholar
  29. Doyle KP, Simon RP, Stenzel-Poore MP (2008) Mechanisms of ischemic brain damage. Neuropharmacology 55:310–318PubMedPubMedCentralCrossRefGoogle Scholar
  30. Du Y, Shi L, Li J, Xiong J, Li B, Fan X (2011) Angiogenesis and improved cerebral blood flow in the ischemic boundary area were detected after electroacupuncture treatment to rats with ischemic stroke. Neurol Res 33:101–107PubMedCrossRefGoogle Scholar
  31. Faraco G, Moraga A, Moore J, Anrather J, Pickel VM, Iadecola C (2013) Circulating endothelin-1 alters critical mechanisms regulating cerebral microcirculation. Hypertension 62:759–766PubMedCrossRefGoogle Scholar
  32. Feng X, Yang S, Liu J, Huang J, Peng J, Lin J, Tao J, Chen L (2013) Electroacupuncture ameliorates cognitive impairment through inhibition of NF-kappaB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats. Mol Med Rep 7:1516–1522PubMedCrossRefGoogle Scholar
  33. Furness DN, Dehnes Y, Akhtar AQ, Rossi DJ, Hamann M, Grutle NJ, Gundersen V, Holmseth S, Lehre KP, Ullensvang K, Wojewodzic M, Zhou Y, Attwell D, Danbolt NC (2008) A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2). Neuroscience 157:80–94PubMedPubMedCentralCrossRefGoogle Scholar
  34. Furukawa K, Fu W, Li Y, Witke W, Kwiatkowski DJ, Mattson MP (1997) The actin-severing protein gelsolin modulates calcium channel and NMDA receptor activities and vulnerability to excitotoxicity in hippocampal neurons. J Neurosci 17:8178–8186PubMedGoogle Scholar
  35. Gan P, Cheng JS, Ng YK, Ling EA (2005) Role of GABA in electro-acupuncture therapy on cerebral ischemia induced by occlusion of the middle cerebral artery in rats. Neurosci Lett 383:317–321PubMedCrossRefGoogle Scholar
  36. Gao H, Guo J, Zhao P, Cheng J (2002) The neuroprotective effects of electroacupuncture on focal cerebral ischemia in monkey. Acupunct Electrother Res 27:45–57PubMedCrossRefGoogle Scholar
  37. Guo F, Song W, Jiang T, Liu L, Wang F, Zhong H, Yin H, Wang Q, Xiong L (2014) Electroacupuncture pretreatment inhibits NADPH oxidase-mediated oxidative stress in diabetic mice with cerebral ischemia. Brain Res 1573:84–91PubMedCrossRefGoogle Scholar
  38. Guo Z, Zhang L, Wu Y, Li M, Yang X, He Z, Wu Z, Hu Y, Jia J (2015) The role of glutamate transporter-1 in the acquisition of brain ischaemic tolerance in rats induced by electro-acupuncture pre-treatment. Brain Inj 29:396–402PubMedCrossRefGoogle Scholar
  39. Halestrap AP, Meredith D (2004) The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447:619–628PubMedCrossRefGoogle Scholar
  40. Han X, Huang X, Wang Y, Chen H (2010) A study of astrocyte activation in the periinfarct region after cerebral ischemia with electroacupuncture. Brain Inj 24:773–779PubMedCrossRefGoogle Scholar
  41. Han B, Lu Y, Zhao H, Wang Y, Li L, Wang T (2015) Electroacupuncture modulated the inflammatory reaction in MCAO rats via inhibiting the TLR4/NF-kappaB signaling pathway in microglia. Int J Clin Exp Pathol 8:11199–11205PubMedPubMedCentralGoogle Scholar
  42. Hartig W, Bauer A, Brauer K, Grosche J, Hortobagyi T, Penke B, Schliebs R, Harkany T (2002) Functional recovery of cholinergic basal forebrain neurons under disease conditions: old problems, new solutions? Rev Neurosci 13:95–165PubMedCrossRefGoogle Scholar
  43. van der Hel WS, Notenboom RG, Bos IW, van Rijen PC, van Veelen CW, de Graan PN (2005) Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology 64:326–333PubMedCrossRefGoogle Scholar
  44. Hong J, Wu G, Zou Y, Tao J, Chen L (2013) Electroacupuncture promotes neurological functional recovery via the retinoic acid signaling pathway in rats following cerebral ischemia-reperfusion injury. Int J Mol Med 31:225–231PubMedCrossRefGoogle Scholar
  45. Hsieh CL, Chang QY, Lin IH, Lin JG, Liu CH, Tang NY, Lane HY (2006) The study of electroacupuncture on cerebral blood flow in rats with and without cerebral ischemia. Am J Chin Med 34:351–361PubMedCrossRefGoogle Scholar
  46. Hsiu H, Huang SM, Chen CT, Hsu CL, Hsu WC (2011) Acupuncture stimulation causes bilaterally different microcirculatory effects in stroke patients. Microvasc Res 81:289–294PubMedCrossRefGoogle Scholar
  47. Hsiu H, Hsu CL, Chen CT, Hsu WC, Lin FC (2013) Effects of acupuncture on the harmonic components of the radial arterial blood-pressure waveform in stroke patients. Biorheology 50:69–81PubMedGoogle Scholar
  48. Huang L, Chen N, Ge M, Zhu Y, Guan S, Wang JH (2010) Ca2+ and acidosis synergistically lead to the dysfunction of cortical GABAergic neurons during ischemia. Biochem Biophys Res Commun 394:709–714PubMedCrossRefGoogle Scholar
  49. Huang Y, Tang C, Wang S, Lu Y, Shen W, Yang J, Chen J, Lin R, Cui S, Xiao H, Qu S, Lai X, Shan B (2012) Acupuncture regulates the glucose metabolism in cerebral functional regions in chronic stage ischemic stroke patients--a PET-CT cerebral functional imaging study. BMC Neurosci 13:75PubMedPubMedCentralCrossRefGoogle Scholar
  50. Huang Y, Chen JQ, Lai XS, Tang CZ, Yang JJ, Chen H, Wu JX, Xiao HL, Qu SS, Zhang YD, Zhang ZJ (2013) Lateralisation of cerebral response to active acupuncture in patients with unilateral ischaemic stroke: an fMRI study. Acupunct Med 31:290–296PubMedCrossRefGoogle Scholar
  51. Huang J, Ye X, You Y, Liu W, Gao Y, Yang S, Peng J, Hong Z, Tao J, Chen L (2014) Electroacupuncture promotes neural cell proliferation in vivo through activation of the ERK1/2 signaling pathway. Int J Mol Med 33:1547–1553PubMedCrossRefGoogle Scholar
  52. Hwang IK, Chung JY, Yoo DY, Yi SS, Youn HY, Seong JK, Yoon YS (2010) Comparing the effects of acupuncture and electroacupuncture at Zusanli and Baihui on cell proliferation and neuroblast differentiation in the rat hippocampus. J Vet Med Sci 72:279–284PubMedCrossRefGoogle Scholar
  53. Igloffstein J, Vogel P (1991) Subacute AIDS-related lumbosacral radiculopathy: a bacterial infection? J Neurol 238:239–241PubMedCrossRefGoogle Scholar
  54. Jiang Y, Yang S, Tao J, Lin Z, Ye X, You Y, Peng J, Hong Z, Chen L (2016) Opposing needling promotes behavior recovery and exerts neuroprotection via the cAMP/PKA/CREB signal transduction pathway in transient MCAO rats. Mol Med Rep 13:2060–2070PubMedPubMedCentralCrossRefGoogle Scholar
  55. Jin Z, Liang J, Wang J, Kolattukudy PE (2013) Delayed brain ischemia tolerance induced by electroacupuncture pretreatment is mediated via MCP-induced protein 1. J Neuroinflammation 10:63PubMedPubMedCentralGoogle Scholar
  56. Jung YS, Lee SW, Park JH, Seo HB, Choi BT, Shin HK (2016) Electroacupuncture preconditioning reduces ROS generation with NOX4 down-regulation and ameliorates blood-brain barrier disruption after ischemic stroke. J Biomed Sci 23:32PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kahles T, Luedike P, Endres M, Galla HJ, Steinmetz H, Busse R, Neumann-Haefelin T, Brandes RP (2007) NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke 38:3000–3006PubMedCrossRefGoogle Scholar
  58. Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, Feng L, Meyer BC, Olson S, Schwamm LH, Yoo AJ, Marshall RS, Meyers PM, Yavagal DR, Wintermark M, Guzy J, Starkman S, Saver JL, Investigators MR (2013) A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 368:914–923PubMedPubMedCentralCrossRefGoogle Scholar
  59. Kim EH, Kim YJ, Lee HJ, Huh Y, Chung JH, Seo JC, Kang JE, Lee HJ, Yim SV, Kim CJ (2001) Acupuncture increases cell proliferation in dentate gyrus after transient global ischemia in gerbils. Neurosci Lett 297:21–24PubMedCrossRefGoogle Scholar
  60. Kim EH, Jang MH, Shin MC, Lim BV, Kim HB, Kim YJ, Chung JH, Kim CJ (2002) Acupuncture increases cell proliferation and neuropeptide Y expression in dentate gyrus of streptozotocin-induced diabetic rats. Neurosci Lett 327:33–36PubMedCrossRefGoogle Scholar
  61. Kim MW, Chung YC, Jung HC, Park MS, Han YM, Chung YA, Maeng LS, Park SI, Lim J, Im WS, Chung JY, Kim M, Mook I, Kim M (2012) Electroacupuncture enhances motor recovery performance with brain-derived neurotrophic factor expression in rats with cerebral infarction. Acupunct Med 30:222–226PubMedCrossRefGoogle Scholar
  62. Kim JH, Choi KH, Jang YJ, Bae SS, Shin BC, Choi BT, Shin HK (2013a) Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice. PLoS One 8:e56736PubMedPubMedCentralCrossRefGoogle Scholar
  63. Kim JH, Choi KH, Jang YJ, Kim HN, Bae SS, Choi BT, Shin HK (2013b) Electroacupuncture preconditioning reduces cerebral ischemic injury via BDNF and SDF-1alpha in mice. BMC Complement Altern Med 13:22PubMedPubMedCentralCrossRefGoogle Scholar
  64. Kim YR, Kim HN, Jang JY, Park C, Lee JH, Shin HK, Choi YH, Choi BT (2013c) Effects of electroacupuncture on apoptotic pathways in a rat model of focal cerebral ischemia. Int J Mol Med 32:1303–1310PubMedCrossRefGoogle Scholar
  65. Kim YR, Kim HN, Ahn SM, Choi YH, Shin HK, Choi BT (2014) Electroacupuncture promotes post-stroke functional recovery via enhancing endogenous neurogenesis in mouse focal cerebral ischemia. PLoS One 9:e90000PubMedPubMedCentralCrossRefGoogle Scholar
  66. Kokaia Z, Lindvall O (2003) Neurogenesis after ischaemic brain insults. Curr Opin Neurobiol 13:127–132PubMedCrossRefGoogle Scholar
  67. Kwak S, Weiss JH (2006) Calcium-permeable AMPA channels in neurodegenerative disease and ischemia. Curr Opin Neurobiol 16:281–287PubMedCrossRefGoogle Scholar
  68. Lan L, Tao J, Chen A, Xie G, Huang J, Lin J, Peng J, Chen L (2013) Electroacupuncture exerts anti-inflammatory effects in cerebral ischemia-reperfusion injured rats via suppression of the TLR4/NF-kappaB pathway. Int J Mol Med 31:75–80PubMedCrossRefGoogle Scholar
  69. Lee GJ, Yin CS, Choi SK, Choi S, Yang JS, Lee H, Park HK (2010) Acupuncture attenuates extracellular glutamate level in global ischemia model of rat. Neurol Res 32(Suppl 1):79–83PubMedCrossRefGoogle Scholar
  70. Lee JY, Lee HE, Kang SR, Choi HY, Ryu JH, Yune TY (2014) Fluoxetine inhibits transient global ischemia-induced hippocampal neuronal death and memory impairment by preventing blood-brain barrier disruption. Neuropharmacology 79:161–171PubMedCrossRefGoogle Scholar
  71. Lee S, Kim W, Park J, Jang HH, Lee SM, Woo JS, Kim HS, Lee KH, Kwon YJ, Lee U, Kim JB, Kim WS, Kim KS (2015) Effects of electroacupuncture on endothelial function and circulating endothelial progenitor cells in patients with cerebral infarction. Clin Exp Pharmacol Physiol 42:822–827PubMedCrossRefGoogle Scholar
  72. Li G, Yang ES (2011) An fMRI study of acupuncture-induced brain activation of aphasia stroke patients. Complement Ther Med 19(Suppl 1):S49–S59PubMedCrossRefGoogle Scholar
  73. Li G, Jack CR Jr, Yang ES (2006) An fMRI study of somatosensory-implicated acupuncture points in stable somatosensory stroke patients. J Magn Reson Imaging 24:1018–1024PubMedCrossRefGoogle Scholar
  74. Li M, Peng J, Song Y, Liang H, Mei Y, Fang Y (2012) Electro-acupuncture combined with transcranial magnetic stimulation improves learning and memory function of rats with cerebral infarction by inhibiting neuron cell apoptosis. J Huazhong Univ Sci Technolog Med Sci 32:746–749PubMedCrossRefGoogle Scholar
  75. Li J, He J, Du Y, Cui J, Ma Y, Zhang X (2014) Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic injury via Angiotensin II its receptors-mediated mechanism in rats. BMC Complement Altern Med 14:441PubMedPubMedCentralCrossRefGoogle Scholar
  76. Li F, Yan CQ, Lin LT, Li H, Zeng XH, Liu Y, Du SQ, Zhu W, Liu CZ (2015a) Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats. BMC Complement Altern Med 15:133PubMedPubMedCentralCrossRefGoogle Scholar
  77. Li MK, Li YJ, Zhang GF, Chen JQ, Zhang JP, Qi J, Huang Y, Lai XS, Tang CZ (2015b) Acupuncture for ischemic stroke: cerebellar activation may be a central mechanism following Deqi. Neural Regen Res 10:1997–2003PubMedPubMedCentralCrossRefGoogle Scholar
  78. Li Y, Wang Y, Zhang H, Wu P, Huang W (2015c) The effect of acupuncture on the motor function and white matter microstructure in ischemic stroke patients. Evid Based Complement Alternat Med eCAM 2015:164792PubMedGoogle Scholar
  79. Liang J, Wang J, Azfer A, Song W, Tromp G, Kolattukudy PE, Fu M (2008) A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages. J Biol Chem 283:6337–6346PubMedCrossRefGoogle Scholar
  80. Lin YW, Hsieh CL (2010) Electroacupuncture at Baihui acupoint (GV20) reverses behavior deficit and long-term potentiation through N-methyl-d-aspartate and transient receptor potential vanilloid subtype 1 receptors in middle cerebral artery occlusion rats. J Integr Neurosci 9:269–282PubMedCrossRefGoogle Scholar
  81. Lin R, Lin Y, Tao J, Chen B, Yu K, Chen J, Li X, Chen LD (2015) Electroacupuncture ameliorates learning and memory in rats with cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting p-CREB expression in the hippocampus. Mol Med Rep 12:6807–6814PubMedCrossRefGoogle Scholar
  82. Lin D, Lin LL, Sutherland K, Cao CH (2016) Manual acupuncture at the SJ5 (Waiguan) acupoint shows neuroprotective effects by regulating expression of the anti-apoptotic gene Bcl-2. Neural Regen Res 11:305–311PubMedPubMedCentralCrossRefGoogle Scholar
  83. Liu Q (2004) Effects of acupuncture on hemorheology, blood lipid content and nail fold microcirculation in multiple infarct dementia patients. J Tradit Chin Med 24:219–223PubMedGoogle Scholar
  84. Liu CZ, Yu JC, Zhang XZ, Fu WW, Wang T, Han JX (2006) Acupuncture prevents cognitive deficits and oxidative stress in cerebral multi-infarction rats. Neurosci Lett 393:45–50PubMedCrossRefGoogle Scholar
  85. Liu YP, Lang BT, Baskaya MK, Dempsey RJ, Vemuganti R (2009) The potential of neural stem cells to repair stroke-induced brain damage. Acta Neuropathol 117:469–480PubMedCrossRefGoogle Scholar
  86. Liu CZ, Li ZG, Wang DJ, Shi GX, Liu LY, Li QQ, Li C (2013a) Effect of acupuncture on hippocampal ref-1 expression in cerebral multi-infarction rats. Neurol Sci 34:305–312PubMedCrossRefGoogle Scholar
  87. Liu H, Shen X, Tang H, Li J, Xiang T, Yu W (2013b) Using microPET imaging in quantitative verification of the acupuncture effect in ischemia stroke treatment. Sci Rep 3:1070PubMedPubMedCentralCrossRefGoogle Scholar
  88. Liu F, Jiang YJ, Zhao HJ, Yao LQ, Chen LD (2015a) Electroacupuncture ameliorates cognitive impairment and regulates the expression of apoptosis-related genes Bcl-2 and Bax in rats with cerebral ischaemia-reperfusion injury. Acupunct Med 33:478–484PubMedCrossRefGoogle Scholar
  89. Liu Z, Chen X, Gao Y, Sun S, Yang L, Yang Q, Bai F, Xiong L, Wang Q (2015b) Involvement of GluR2 up-regulation in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptor in mice. Sci Rep 5:9490PubMedPubMedCentralCrossRefGoogle Scholar
  90. Liu W, Wang X, Zheng Y, Shang G, Huang J, Tao J, Chen L (2016a) Electroacupuncture inhibits inflammatory injury by targeting the miR-9-mediated NF-kappaB signaling pathway following ischemic stroke. Mol Med Rep 13:1618–1626PubMedCrossRefGoogle Scholar
  91. Liu W, Wang X, Yang S, Huang J, Xue X, Zheng Y, Shang G, Tao J, Chen L (2016b) Electroacupunctre improves motor impairment via inhibition of microglia-mediated neuroinflammation in the sensorimotor cortex after ischemic stroke. Life Sci 151:313–322PubMedCrossRefGoogle Scholar
  92. Liu W, Shang G, Yang S, Huang J, Xue X, Lin Y, Zheng Y, Wang X, Wang L, Lin R, Tao J, Chen L (2016c) Electroacupuncture protects against ischemic stroke by reducing autophagosome formation and inhibiting autophagy through the mTORC1-ULK1 complex-Beclin1 pathway. Int J Mol Med 37:309–318PubMedCrossRefGoogle Scholar
  93. Lu HC, Mackie K (2016) An introduction to the endogenous cannabinoid system. Biol Psychiatry 79:516–525PubMedCrossRefGoogle Scholar
  94. Lu T, Luo Y, Sun H, Qin W, Li Y (2013) Electroacupuncture improves behavioral recovery and increases SCF/c-kit expression in a rat model of focal cerebral ischemia/reperfusion. Neurol Sci 34:487–495PubMedCrossRefGoogle Scholar
  95. Lu Y, Zhao H, Wang Y, Han B, Wang T, Zhao H, Cui K, Wang S (2015) Electro-acupuncture up-regulates astrocytic MCT1 expression to improve neurological deficit in middle cerebral artery occlusion rats. Life Sci 134:68–72PubMedCrossRefGoogle Scholar
  96. Lu L, Zhang XG, Zhong LL, Chen ZX, Li Y, Zheng GQ, Bian ZX (2016) Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis. Sci Rep 6:19521PubMedPubMedCentralCrossRefGoogle Scholar
  97. Luo Y, Xu NG, Yi W, Yu T, Yang ZH (2011) Study on the correlation between synaptic reconstruction and astrocyte after ischemia and the influence of electroacupuncture on rats. Chin J Integr Med 17:750–757PubMedCrossRefGoogle Scholar
  98. Luo D, Fan X, Ma C, Fan T, Wang X, Chang N, Li L, Zhang Y, Meng Z, Wang S, Shi X (2014) A study on the effect of neurogenesis and regulation of GSK3beta/PP2A expression in acupuncture treatment of neural functional damage caused by focal ischemia in MCAO rats. Evid Based Complement Alternat Med eCAM 2014:962343PubMedGoogle Scholar
  99. Ma J, Luo Y (2008) 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 28:217–222PubMedCrossRefGoogle Scholar
  100. Ma L, Zhu Z, Zhao Y, Hou L, Wang Q, Xiong L, Zhu X, Jia J, Chen S (2011) Cannabinoid receptor type 2 activation yields delayed tolerance to focal cerebral ischemia. Curr Neurovasc Res 8:145–152PubMedCrossRefGoogle Scholar
  101. Ma R, Yuan B, Du J, Wang L, Ma L, Liu S, Shu Q, Sun H (2016) Electroacupuncture alleviates nerve injury after cerebra ischemia in rats through inhibiting cell apoptosis and changing the balance of MMP-9/TIMP-1 expression. Neurosci Lett 633:158–164PubMedCrossRefGoogle Scholar
  102. Mauch DH, Nagler K, Schumacher S, Goritz C, Muller EC, Otto A, Pfrieger FW (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294:1354–1357PubMedCrossRefGoogle Scholar
  103. Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250PubMedCrossRefGoogle Scholar
  104. Muir KW, Lees KR (2003) Excitatory amino acid antagonists for acute stroke Cochrane Database Syst Rev. doi: 10.1002/14651858.CD001244
  105. Mukherjee D, Patil CG (2011) Epidemiology and the global burden of stroke. World Neurosurg 76:S85–S90PubMedCrossRefGoogle Scholar
  106. Nakamura H (2004) Thioredoxin as a key molecule in redox signaling. Antioxid Redox Signal 6:15–17PubMedCrossRefGoogle Scholar
  107. Nathan C, Ding A (2010) SnapShot: reactive oxygen intermediates (ROI). Cell 140:951–95.e952PubMedCrossRefGoogle Scholar
  108. Navaratna D, Guo S, Arai K, Lo EH (2009) Mechanisms and targets for angiogenic therapy after stroke. Cell Adhes Migr 3:216–223CrossRefGoogle Scholar
  109. Neumann S, Shields NJ, Balle T, Chebib M, Clarkson AN (2015) Innate immunity and inflammation post-stroke: an alpha7-nicotinic agonist perspective. Int J Mol Sci 16:29029–29046PubMedPubMedCentralCrossRefGoogle Scholar
  110. Nozaki K, Nishimura M, Hashimoto N (2001) Mitogen-activated protein kinases and cerebral ischemia. Mol Neurobiol 23:1–19PubMedCrossRefGoogle Scholar
  111. Otsuka S, Sakakima H, Sumizono M, Takada S, Terashi T, Yoshida Y (2016) The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats. Behav Brain Res 303:9–18PubMedCrossRefGoogle Scholar
  112. Ou YW, Han L, Da CD, Huang YL, Cheng JS (2001) Influence of acupuncture upon expressing levels of basic fibroblast growth factor in rat brain following focal cerebral ischemia--evaluated by time-resolved fluorescence immunoassay. Neurol Res 23:47–50PubMedCrossRefGoogle Scholar
  113. Pan T, Kondo S, Le W, Jankovic J (2008) The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 131:1969–1978PubMedCrossRefGoogle Scholar
  114. Pan S, Zhan X, Su X, Guo L, Lv L, Su B (2011) Proteomic analysis of serum proteins in acute ischemic stroke patients treated with acupuncture. Exp Biol Med 236:325–333CrossRefGoogle Scholar
  115. Pang J, Itano T, Sumitani K, Negi T, Miyamoto O (2003) Electroacupuncture attenuates both glutamate release and hyperemia after transient ischemia in gerbils. Am J Chin Med 31:295–303PubMedCrossRefGoogle Scholar
  116. Paravicini TM, Touyz RM (2008) NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diabetes Care 31(Suppl 2):S170–S180PubMedCrossRefGoogle Scholar
  117. Park J, Hopwood V, White AR, Ernst E (2001) Effectiveness of acupuncture for stroke: a systematic review. J Neurol 248:558–563PubMedCrossRefGoogle Scholar
  118. Peng Y, Wang H, Sun J, Chen L, Xu M, Chu J (2012) Electroacupuncture reduces injury to the blood-brain barrier following cerebral ischemia/reperfusion injury. Neural Regen Res 7:2901–2906PubMedPubMedCentralGoogle Scholar
  119. Pias-Peleteiro J, Perez-Mato M, Lopez-Arias E, Rodriguez-Yanez M, Blanco M, Campos F, Castillo J, Sobrino T (2016) Increased endothelial progenitor cell levels are associated with good outcome in intracerebral hemorrhage. Sci Rep 6:28724PubMedPubMedCentralCrossRefGoogle Scholar
  120. Qi J, Chen J, Huang Y, Lai X, Tang C, Yang J, Chen H, Qu S (2014) Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study. Neural Regen Res 9:293–300PubMedPubMedCentralCrossRefGoogle Scholar
  121. Qin WY, Luo Y, Chen L, Tao T, Li Y, Cai YL, Li YH (2013) Electroacupuncture could regulate the NF-kappaB signaling pathway to ameliorate the inflammatory injury in focal cerebral ischemia/reperfusion model rats. Evid Based Complement Alternat Med eCAM 2013:924541PubMedGoogle Scholar
  122. Ratmansky M, Levy A, Messinger A, Birg A, Front L, Treger I (2016) The effects of acupuncture on cerebral Blood flow in post-stroke patients: a randomized controlled trial. J Altern Complement Med 22:33–37PubMedPubMedCentralCrossRefGoogle Scholar
  123. Ren L, Zhang WA, Fang NY, Wang JX (2008) The influence of electro-acupuncture on neural plasticity in acute cerebral infarction. Neurol Res 30:985–989PubMedCrossRefGoogle Scholar
  124. Ren L, Wang YK, Fang YN, Zhang AW, Li XL (2010a) Effect of electroacupuncture therapy on the expression of Na(v)1.1 and Na(v)1.6 in rat after acute cerebral ischemia. Neurol Res 32:1110–1116PubMedCrossRefGoogle Scholar
  125. Ren L, Fang Y, Zhang A, Li X, Wang X, Yin Z, Miao J (2010b) Effect of electroacupuncture on the expression of Nav1.1 in rat after acute cerebral ischemia. Neurol Res 32:763–769PubMedCrossRefGoogle Scholar
  126. Roux PP, Barker PA (2002) Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol 67:203–233PubMedCrossRefGoogle Scholar
  127. Sahota P, Savitz SI (2011) Investigational therapies for ischemic stroke: neuroprotection and neurorecovery. Neurotherapeutics 8:434–451PubMedPubMedCentralCrossRefGoogle Scholar
  128. Schaechter JD, Connell BD, Stason WB, Kaptchuk TJ, Krebs DE, Macklin EA, Schnyer RN, Stein J, Scarborough DM, Parker SW, McGibbon CA, Wayne PM (2007) Correlated change in upper limb function and motor cortex activation after verum and sham acupuncture in patients with chronic stroke. J Altern Complement Med 13:527–532PubMedCrossRefGoogle Scholar
  129. Schurr A, Payne RS, Miller JJ, Tseng MT, Rigor BM (2001) Blockade of lactate transport exacerbates delayed neuronal damage in a rat model of cerebral ischemia. Brain Res 895:268–272PubMedCrossRefGoogle Scholar
  130. Shen Y, Li M, Wei R, Lou M (2012) Effect of acupuncture therapy for postponing Wallerian degeneration of cerebral infarction as shown by diffusion tensor imaging. J Altern Complement Med 18:1154–1160PubMedPubMedCentralCrossRefGoogle Scholar
  131. Shi GX, Wang XR, Yan CQ, He T, Yang JW, Zeng XH, Xu Q, Zhu W, Du SQ, Liu CZ (2015) Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia. Sci Rep 5:17981PubMedPubMedCentralCrossRefGoogle Scholar
  132. Shih CC, Liao CC, Sun MF, Su YC, Wen CP, Morisky DE, Sung FC, Hsu CY, Lin JG (2015) A retrospective cohort study comparing stroke recurrence rate in ischemic stroke patients with and without acupuncture treatment. Medicine 94:e1572PubMedPubMedCentralCrossRefGoogle Scholar
  133. Shu S, Li CM, You YL, Qian XL, Zhou S, Ling CQ (2016) Electroacupuncture ameliorates cerebral ischemia-reperfusion injury by regulation of autophagy and apoptosis. Evid Based Complement Alternat Med eCAM 2016:7297425PubMedGoogle Scholar
  134. Shuaib A, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM, Diener HC, Ashwood T, Wasiewski WW, Emeribe U, Investigators SIT (2007) NXY-059 for the treatment of acute ischemic stroke. N Engl J Med 357:562–571PubMedCrossRefGoogle Scholar
  135. Siu FK, Lo SC, Leung MC (2004a) Effectiveness of multiple pre-ischemia electro-acupuncture on attenuating lipid peroxidation induced by cerebral ischemia in adult rats. Life Sci 75:1323–1332PubMedCrossRefGoogle Scholar
  136. Siu FK, Lo SC, Leung MC (2004b) Electroacupuncture reduces the extent of lipid peroxidation by increasing superoxide dismutase and glutathione peroxidase activities in ischemic-reperfused rat brains. Neurosci Lett 354:158–162PubMedCrossRefGoogle Scholar
  137. Siu FK, Lo SC, Leung MC (2005) Electro-acupuncture potentiates the disulphide-reducing activities of thioredoxin system by increasing thioredoxin expression in ischemia-reperfused rat brains. Life Sci 77:386–399PubMedCrossRefGoogle Scholar
  138. Song H, Stevens CF, Gage FH (2002) Astroglia induce neurogenesis from adult neural stem cells. Nature 417:39–44PubMedCrossRefGoogle Scholar
  139. Stroke Therapy Academic Industry R (1999) Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 30:2752–2758CrossRefGoogle Scholar
  140. Strong K, Mathers C, Bonita R (2007) Preventing stroke: saving lives around the world. Lancet Neurol 6:182–187PubMedCrossRefGoogle Scholar
  141. Sun N, Zou X, Shi J, Liu X, Li L, Zhao L (2005) Electroacupuncture regulates NMDA receptor NR1 subunit expression via PI3-K pathway in a rat model of cerebral ischemia-reperfusion. Brain Res 1064:98–107PubMedCrossRefGoogle Scholar
  142. Sun S, Chen X, Gao Y, Liu Z, Zhai Q, Xiong L, Cai M, Wang Q (2016) Mn-SOD upregulation by Electroacupuncture attenuates ischemic oxidative damage via CB1R-mediated STAT3 phosphorylation. Mol Neurobiol 53:331–343PubMedCrossRefGoogle Scholar
  143. Szymanska P, Martin KR, MacKeigan JP, Hlavacek WS, Lipniacki T (2015) Computational analysis of an autophagy/translation switch based on mutual inhibition of MTORC1 and ULK1. PLoS One 10:e0116550PubMedPubMedCentralCrossRefGoogle Scholar
  144. Takano T, Oberheim N, Cotrina ML, Nedergaard M (2009) Astrocytes and ischemic injury. Stroke 40:S8–12PubMedCrossRefGoogle Scholar
  145. Tao J, Xue XH, Chen LD, Yang SL, Jiang M, Gao YL, Wang XB (2010) Electroacupuncture improves neurological deficits and enhances proliferation and differentiation of endogenous nerve stem cells in rats with focal cerebral ischemia. Neurol Res 32:198–204PubMedCrossRefGoogle Scholar
  146. Tao J, Zheng Y, Liu W, Yang S, Huang J, Xue X, Shang G, Wang X, Lin R, Chen L (2016) Electro-acupuncture at LI11 and ST36 acupoints exerts neuroprotective effects via reactive astrocyte proliferation after ischemia and reperfusion injury in rats. Brain Res Bull 120:14–24PubMedCrossRefGoogle Scholar
  147. Wang SJ, Omori N, Li F, Jin G, Zhang WR, Hamakawa Y, Sato K, Nagano I, Shoji M, Abe K (2002) Potentiation of Akt and suppression of caspase-9 activations by electroacupuncture after transient middle cerebral artery occlusion in rats. Neurosci Lett 331:115–118PubMedCrossRefGoogle Scholar
  148. Wang SJ, Omori N, Li F, Jin G, Hamakawa Y, Sato K, Nagano I, Shoji M, Abe K (2003) Functional improvement by electro-acupuncture after transient middle cerebral artery occlusion in rats. Neurol Res 25:516–521PubMedCrossRefGoogle Scholar
  149. Wang Q, Peng Y, Chen S, Gou X, Hu B, Du J, Lu Y, Xiong L (2009a) Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system. Stroke 40:2157–2164PubMedCrossRefGoogle Scholar
  150. Wang T, Liu CZ, Yu JC, Jiang W, Han JX (2009b) Acupuncture protected cerebral multi-infarction rats from memory impairment by regulating the expression of apoptosis related genes Bcl-2 and Bax in hippocampus. Physiol Behav 96:155–161PubMedCrossRefGoogle Scholar
  151. Wang JY, Xia Q, Chu KT, Pan J, Sun LN, Zeng B, Zhu YJ, Wang Q, Wang K, Luo BY (2011a) Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in rat is prevented by 3-methyladenine: a widely used inhibitor of autophagy. J Neuropathol Exp Neurol 70:314–322PubMedCrossRefGoogle Scholar
  152. Wang Q, Li X, Chen Y, Wang F, Yang Q, Chen S, Min Y, Li X, Xiong L (2011b) Activation of epsilon protein kinase C-mediated anti-apoptosis is involved in rapid tolerance induced by electroacupuncture pretreatment through cannabinoid receptor type 1. Stroke 42:389–396PubMedCrossRefGoogle Scholar
  153. Wang Q, Wang F, Li X, Yang Q, Li X, Xu N, Huang Y, Zhang Q, Gou X, Chen S, Xiong L (2012) Electroacupuncture pretreatment attenuates cerebral ischemic injury through alpha7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats. J Neuroinflammation 9:24PubMedPubMedCentralGoogle Scholar
  154. Wang WW, Xie CL, Lu L, Zheng GQ (2014) A systematic review and meta-analysis of Baihui (GV20)-based scalp acupuncture in experimental ischemic stroke. Sci Rep 4:3981PubMedPubMedCentralCrossRefGoogle Scholar
  155. Wang JH, Zhao M, Bao YC, Shang JF, Yan Q, Zhang ZC, Du XZ, Jiang H, Zhang WD (2016a) Effect of scalp-acupuncture treatment on levels of serum high-sensitivity C-reactive protein, and pro-inflammatory cytokines in patients with acute cerebral infarction. Zhen Ci Yan Jiu 41:80–84PubMedGoogle Scholar
  156. Wang Y, Shen Y, Lin HP, Li Z, Chen YY, Wang S (2016b) Large-conductance ca(2+)-activated K(+) channel involvement in suppression of cerebral ischemia/reperfusion injury after electroacupuncture at Shuigou (GV26) acupoint in rats. Neural Regen Res 11:957–962PubMedPubMedCentralGoogle Scholar
  157. Wei H, Yao X, Yang L, Wang S, Guo F, Zhou H, Marsicano G, Wang Q, Xiong L (2014) Glycogen synthase kinase-3beta is involved in electroacupuncture pretreatment via the cannabinoid CB1 receptor in ischemic stroke. Mol Neurobiol 49:326–336PubMedCrossRefGoogle Scholar
  158. Wu XD, Du LN, Wu GC, Cao XD (2001) Effects of electroacupuncture on blood-brain barrier after cerebral ischemia-reperfusion in rat. Acupunct Electrother Res 26:1–9PubMedCrossRefGoogle Scholar
  159. Wu Z, Zou Z, Zou R, Zhou X, Cui S (2015) Electroacupuncture pretreatment induces tolerance against cerebral ischemia/reperfusion injury through inhibition of the autophagy pathway. Mol Med Rep 11:4438–4446PubMedCrossRefGoogle Scholar
  160. Xie G, Yang S, Chen A, Lan L, Lin Z, Gao Y, Huang J, Lin J, Peng J, Tao J, Chen L (2013) Electroacupuncture at Quchi and Zusanli treats cerebral ischemia-reperfusion injury through activation of ERK signaling. Exp Ther Med 5:1593–1597PubMedPubMedCentralCrossRefGoogle Scholar
  161. Xie Z, Cui F, Zou Y, Bai L (2014) Acupuncture enhances effective connectivity between cerebellum and primary sensorimotor cortex in patients with stable recovery stroke. Evid Based Complement Alternat Med eCAM 2014:603909PubMedGoogle Scholar
  162. Xin Z, Xue-Ting L, De-Ying K (2015) GRADE in systematic reviews of acupuncture for stroke rehabilitation: recommendations based on high-quality evidence. Sci Rep 5:16582PubMedPubMedCentralCrossRefGoogle Scholar
  163. Xu Q, Liu T, Chen S, Gao Y, Wang J, Qiao L, Liu J (2012) The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region. Neural Regen Res 7:1378–1385PubMedPubMedCentralGoogle Scholar
  164. Xu MS, Zhang SJ, Zhao D, Liu CY, Li CZ, Chen CY, Li LH, Li MZ, Xu J, Ge LB (2013a) Electroacupuncture-induced neuroprotection against cerebral ischemia in rats: role of the dopamine D2 receptor. Evid Based Complement Alternat Med eCAM 2013:137631PubMedGoogle Scholar
  165. Xu Q, Liu T, Chen S, Gao Y, Wang J, Qiao L, Liu J (2013b) Correlation between the cumulative analgesic effect of electroacupuncture intervention and synaptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica. Neural Regen Res 8:218–225PubMedPubMedCentralGoogle Scholar
  166. Xu H, Zhang Y, Sun H, Chen S, Wang F (2014a) Effects of acupuncture at GV20 and ST36 on the expression of matrix metalloproteinase 2, aquaporin 4, and aquaporin 9 in rats subjected to cerebral ischemia/reperfusion injury. PLoS One 9:e97488PubMedPubMedCentralCrossRefGoogle Scholar
  167. Xu H, Sun H, Chen SH, Zhang YM, Piao YL, Gao Y (2014b) Effects of acupuncture at Baihui (DU20) and Zusanli (ST36) on the expression of heat shock protein 70 and tumor necrosis factor alpha in the peripheral serum of cerebral ischemia-reperfusion-injured rats. Chin J Integr Med 20:369–374PubMedCrossRefGoogle Scholar
  168. Xue X, You Y, Tao J, Ye X, Huang J, Yang S, Lin Z, Hong Z, Peng J, Chen L (2014) Electro-acupuncture at points of Zusanli and Quchi exerts anti-apoptotic effect through the modulation of PI3K/Akt signaling pathway. Neurosci Lett 558:14–19PubMedCrossRefGoogle Scholar
  169. Yang Y, Rosenberg GA (2011) Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 42:3323–3328PubMedPubMedCentralCrossRefGoogle Scholar
  170. Yang B, Zhang C, Feng G, Chen H (2007) The effect of acupuncture on plasma endothelin content in cerebral infarction patients--a clinical study. J Tradit Chin Med 27:197–198PubMedGoogle Scholar
  171. Yu H, Chen P, Yang Z, Luo W, Pi M, Wu Y, Wang L (2014) Electro-acupuncture at conception and governor vessels and transplantation of umbilical cord blood-derived mesenchymal stem cells for treating cerebral ischemia/reperfusion injury. Neural Regen Res 9:84–91PubMedPubMedCentralCrossRefGoogle Scholar
  172. Zhan J, Qin W, Zhang Y, Jiang J, Ma H, Li Q, Luo Y (2016) Upregulation of neuronal zinc finger protein A20 expression is required for electroacupuncture to attenuate the cerebral inflammatory injury mediated by the nuclear factor-kB signaling pathway in cerebral ischemia/reperfusion rats. J Neuroinflammation 13:258PubMedPubMedCentralCrossRefGoogle Scholar
  173. Zhang FH (2010) Effects of acupuncture at 7-9 am and 3-5 pm on plasma thromboxane and prostaglandin in patients with ischemic cerebrovascular disease. J Tradit Chin Med 30:9–12PubMedCrossRefGoogle Scholar
  174. Zhang SH, Liu M, Asplund K, Li L (2005) Acupuncture for acute stroke. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD003317.pub2
  175. Zhang HX, Liu LG, Zhou L, Huang H, Li X, Yang M (2007) Effect of scalp acupuncture on inflammatory response in rats with acute cerebral ischemia-reperfusion injury. Zhong Xi Yi Jie He Xue Bao 5:686–691PubMedCrossRefGoogle Scholar
  176. Zhang RL, Zhang ZG, Chopp M (2008) Ischemic stroke and neurogenesis in the subventricular zone. Neuropharmacology 55:345–352PubMedPubMedCentralCrossRefGoogle Scholar
  177. Zhang F, Wu Y, Jia J (2011a) Electro-acupuncture can alleviate the cerebral oedema of rat after ischemia. Brain Inj 25:895–900PubMedCrossRefGoogle Scholar
  178. Zhang LD, Yu D, Qu Y, Wang Z, Gao Y, Pan Q, Wang J, Guan HQ (2011b) Effect of eye-acupuncture on cerebral intracellular adhesion molecule-1 expression in rats with acute cerebral ischemia-reperfusion injury. Zhen ci yan jiu 36:409–413PubMedGoogle Scholar
  179. Zhang S, Li G, Xu X, Chang M, Zhang C, Sun F (2011c) Acupuncture to point Baihui prevents ischemia-induced functional impairment of cortical GABAergic neurons. J Neurol Sci 307:139–143PubMedCrossRefGoogle Scholar
  180. Zhang X, Wu B, Nie K, Jia Y, Yu J (2014) Effects of acupuncture on declined cerebral blood flow, impaired mitochondrial respiratory function and oxidative stress in multi-infarct dementia rats. Neurochem Int 65:23–29PubMedCrossRefGoogle Scholar
  181. Zhang C, Wen Y, Fan XN, Tian G, Zhou XY, Deng SZ, Meng ZH (2015) Therapeutic effects of different durations of acupuncture on rats with middle cerebral artery occlusion. Neural Regen Res 10:159–164PubMedPubMedCentralCrossRefGoogle Scholar
  182. Zhao L, Wang Y, Sun N, Liu X, Li L, Shi J (2007) Electroacupuncture regulates TRPM7 expression through the trkA/PI3K pathway after cerebral ischemia-reperfusion in rats. Life Sci 81:1211–1222PubMedCrossRefGoogle Scholar
  183. Zhao L, Shen P, Han Y, Zhang X, Nie K, Cheng H, Kan B, Li G, Yu J, Han J (2011) Effects of acupuncture on glycometabolic enzymes in multi-infarct dementia rats. Neurochem Res 36:693–700PubMedCrossRefGoogle Scholar
  184. Zhao Y, Chen X, Ma L, Zuo Z, Zhu Z, Zhu X, Wang Q, He E, Xiong L, Pei J, Xu L, Hou L, Chen S (2012) Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway. BMC Neurosci 13:111PubMedPubMedCentralCrossRefGoogle Scholar
  185. Zhao Y, Deng B, Li Y, Zhou L, Yang L, Gou X, Wang Q, Chen G, Xu H, Xu L (2015) Electroacupuncture pretreatment attenuates cerebral ischemic injury via Notch pathway-mediated up-regulation of hypoxia inducible factor-1alpha in rats. Cell Mol Neurobiol 35:1093–1103PubMedPubMedCentralCrossRefGoogle Scholar
  186. Zhou F, Guo J, Cheng J, Wu G, Xia Y (2011) Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency. J Appl Physiol 111:1877–1887PubMedPubMedCentralCrossRefGoogle Scholar
  187. Zhou F, Guo J, Cheng J, Wu G, Xia Y (2013a) Effect of electroacupuncture on rat ischemic brain injury: importance of stimulation duration. Evid Based Complement Alternat Med eCAM 2013:878521PubMedGoogle Scholar
  188. Zhou F, Guo J, Cheng J, Wu G, Sun J, Xia Y (2013b) Electroacupuncture and Brain protection against cerebral ischemia: specific effects of Acupoints. Evid Based Complement Alternat Med eCAM 2013:804397PubMedGoogle Scholar
  189. Zhu X, Yin J, Li L, Ma L, Tan H, Deng J, Chen S, Zuo Z (2013) Electroacupuncture preconditioning-induced neuroprotection may be mediated by glutamate transporter type 2. Neurochem Int 63:302–308PubMedPubMedCentralCrossRefGoogle Scholar
  190. Zhu T, Yao Q, Hu X, Chen C, Yao H, Chao J (2015) The role of MCPIP1 in ischemia/reperfusion injury-induced HUVEC migration and apoptosis. Cell Physiol Biochem 37:577–591PubMedCrossRefGoogle Scholar
  191. Zou R, Wu Z, Cui S (2015) Electroacupuncture pretreatment attenuates bloodbrain barrier disruption following cerebral ischemia/reperfusion. Mol Med Rep 12:2027–2034PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Wen Zhu
    • 1
  • Yang Ye
    • 1
    • 2
  • Yi Liu
    • 1
  • Xue-Rui Wang
    • 1
  • Guang-Xia Shi
    • 1
  • Shuai Zhang
    • 1
  • Cun-Zhi Liu
    • 1
    Email author
  1. 1.Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing Key Laboratory of Acupuncture NeuromodulationBeijingChina
  2. 2.Graduate SchoolBeijing University of Chinese MedicineBeijingChina

Personalised recommendations