Skip to main content
SpringerLink
Log in
Book cover

Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke pp 93–108Cite as

Angiogenesis: A Realistic Therapy for Ischemic Stroke

  • Chapter
  • First Online:

  • 863 Accesses

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Angiogenesis is a physiopathologic process where new blood vessels generate from existing vascular endothelial cells to deliver nutrients and oxygen to various organs and tissue. Angiogenesis is strictly regulated by many key anti- or pro-angiogenic factors, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. In human diseases angiogenesis has a dual effect: inhibition of angiogenesis can prevent diseases such as cancer, arthritis, diabetic nephropathy, psoriasis, whereas stimulation of angiogenesis is beneficial in the treatment of wound healing, tissue remodeling, or ischemic heart and brain diseases. Following ischemic stroke, angiogenesis is activated to modify capillary network and acts as an effective self-protective route to achieve restoration or improvement of the reduced regional cerebral blood supply, which is very critical for the stroke outcomes and post-stroke functional recovery both in human and experimental animal models. In this review, we summarize current knowledge about angiogenesis processes following ischemic stroke and potential benefit of future development of therapeutic angiogenic-related treatments.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Schellinger PD, Kaste M, Hacke W. An update on thrombolytic therapy for acute stroke. Curr Opin Neurol. 2004;17(1):69–77.

    Article  CAS  PubMed  Google Scholar 

  2. Schellinger PD, Warach S. Therapeutic time window of thrombolytic therapy following stroke. Curr Atheroscler Rep. 2004;6(4):288–94.

    Article  PubMed  Google Scholar 

  3. Stapf C, Mohr JP. Ischemic stroke therapy. Annu Rev Med. 2002;53:453–75.

    Article  CAS  PubMed  Google Scholar 

  4. Barone FC. Ischemic stroke intervention requires mixed cellular protection of the penumbra. Curr Opin Investig Drugs. 2009;10(3):220–3.

    PubMed  Google Scholar 

  5. Del Zoppo GJ, Milner R, Mabuchi T, Hung S, Wang X, Koziol JA. Vascular matrix adhesion and the blood-brain barrier. Biochem Soc Trans. 2006;34(Pt 6):1261–6.

    PubMed  Google Scholar 

  6. Ginsberg MD. Current status of neuroprotection for cerebral ischemia: synoptic overview. Stroke. 2009;40(3 Suppl):S111–4.

    Article  PubMed  Google Scholar 

  7. Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci. 2003;4(5):399–415.

    Article  CAS  PubMed  Google Scholar 

  8. Yuan J. Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis. 2009;14(4):469–77.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hayashi T, Deguchi K, Nagotani S, Zhang H, Sehara Y, Tsuchiya A, et al. Cerebral ischemia and angiogenesis. Curr Neurovasc Res. 2006;3(2):119–29.

    Article  CAS  PubMed  Google Scholar 

  10. Beck H, Plate KH. Angiogenesis after cerebral ischemia. Acta Neuropathol. 2009;117(5):481–96.

    Article  PubMed  Google Scholar 

  11. Arai K, Jin G, Navaratna D, Lo EH. Brain angiogenesis in developmental and pathological processes: neurovascular injury and angiogenic recovery after stroke. FEBS J. 2009;276(17):4644–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol. 2009;8(5):491–500.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yin KJ, Hamblin M, Chen YE. Non-coding RNAs in cerebral endothelial pathophysiology: emerging roles in stroke. Neurochem Int. 2014;77:9–16.

    Article  CAS  PubMed  Google Scholar 

  14. Yin KJ, Hamblin M, Chen YE. Angiogenesis-regulating microRNAs and ischemic stroke. Curr Vasc Pharmacol. 2015;13(3):352–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Krupinski J, Kaluza J, Kumar P, Kumar S, Wang JM. Some remarks on the growth-rate and angiogenesis of microvessels in ischemic stroke. Morphometric and immunocytochemical studies. Patol Pol. 1993;44(4):203–9.

    CAS  PubMed  Google Scholar 

  16. Krupinski J, Kaluza J, Kumar P, Kumar S, Wang JM. Role of angiogenesis in patients with cerebral ischemic stroke. Stroke. 1994;25(9):1794–8.

    Article  CAS  PubMed  Google Scholar 

  17. Chen YC, Wu JS, Yang ST, Huang CY, Chang C, Sun GY, et al. Stroke, angiogenesis and phytochemicals. Front Biosci. 2012;4:599–610.

    CAS  Google Scholar 

  18. Al Sabti H. Therapeutic angiogenesis in cardiovascular disease. J Cardiothorac Surg. 2007;2:49.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Manoonkitiwongsa PS. Critical questions for preclinical trials on safety and efficacy of vascular endothelial growth factor-based therapeutic angiogenesis for ischemic stroke. CNS Neurol Disord Drug Targets. 2011;10(2):215–34.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, et al. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000;106(7):829–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003;111(12):1843–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang Y, Kilic E, Kilic U, Weber B, Bassetti CL, Marti HH, et al. VEGF overexpression induces post-ischaemic neuroprotection, but facilitates haemodynamic steal phenomena. Brain. 2005;128(Pt 1):52–63.

    PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. Issa R, Krupinski J, Bujny T, Kumar S, Kaluza J, Kumar P. Vascular endothelial growth factor and its receptor, KDR, in human brain tissue after ischemic stroke. Lab Invest. 1999;79(4):417–25.

    CAS  PubMed  Google Scholar 

  25. Kovacs Z, Ikezaki K, Samoto K, Inamura T, Fukui M. VEGF and flt. Expression time kinetics in rat brain infarct. Stroke. 1996;27(10):1865–72; discussion 72–3.

    Article  CAS  PubMed  Google Scholar 

  26. Greenberg DA, Jin K. From angiogenesis to neuropathology. Nature. 2005;438(7070):954–9.

    Article  CAS  PubMed  Google Scholar 

  27. Gunsilius E, Petzer AL, Stockhammer G, Kahler CM, Gastl G. Serial measurement of vascular endothelial growth factor and transforming growth factor-beta1 in serum of patients with acute ischemic stroke. Stroke. 2001;32(1):275–8.

    Article  CAS  PubMed  Google Scholar 

  28. Slevin M, Krupinski J, Slowik A, Kumar P, Szczudlik A, Gaffney J. Serial measurement of vascular endothelial growth factor and transforming growth factor-beta1 in serum of patients with acute ischemic stroke. Stroke. 2000;31(8):1863–70.

    Article  CAS  PubMed  Google Scholar 

  29. Stapor P, Wang X, Goveia J, Moens S, Carmeliet P. Angiogenesis revisited—role and therapeutic potential of targeting endothelial metabolism. J Cell Sci. 2014;127(Pt 20):4331–41.

    Article  CAS  PubMed  Google Scholar 

  30. Stapor PC, Sweat RS, Dashti DC, Betancourt AM, Murfee WL. Pericyte dynamics during angiogenesis: new insights from new identities. J Vasc Res. 2014;51(3):163–74.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ. Hypoxia-induced tumor angiogenic pathway in head and neck cancer: an in vivo study. Cancer Lett. 2005;225(2):297–304.

    Article  CAS  PubMed  Google Scholar 

  32. Shi H. Hypoxia inducible factor 1 as a therapeutic target in ischemic stroke. Curr Med Chem. 2009;16(34):4593–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. Bai YY, Wang L, Chang D, Zhao Z, Lu CQ, Wang G, et al. Synergistic effects of transplanted endothelial progenitor cells and RWJ 67657 in diabetic ischemic stroke models. Stroke. 2015;46(7):1938–46.

    Article  CAS  PubMed  Google Scholar 

  35. Gopinathan G, Milagre C, Pearce OM, Reynolds LE, Hodivala-Dilke K, Leinster DA, et al. Interleukin-6 stimulates defective angiogenesis. Cancer Res. 2015;75(15):3098–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhang ZG, Chopp M. Promoting brain remodeling to aid in stroke recovery. Trends Mol Med. 2015;21(9):543–8.

    Article  PubMed  Google Scholar 

  37. Zhao X, Wang H, Sun G, Zhang J, Edwards NJ, Aronowski J. Neuronal interleukin-4 as a modulator of microglial pathways and ischemic brain damage. J Neurosci. 2015;35(32):11281–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Beck H, Acker T, Wiessner C, Allegrini PR, Plate KH. Expression of angiopoietin-1, angiopoietin-2, and tie receptors after middle cerebral artery occlusion in the rat. Am J Pathol. 2000;157(5):1473–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hayashi T, Noshita N, Sugawara T, Chan PH. Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab. 2003;23(2):166–80.

    Article  CAS  PubMed  Google Scholar 

  40. Marti HJ, Bernaudin M, Bellail A, Schoch H, Euler M, Petit E, et al. Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol. 2000;156(3):965–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yang Y, Salayandia VM, Thompson JF, Yang LY, Estrada EY, Yang Y. Attenuation of acute stroke injury in rat brain by minocycline promotes blood-brain barrier remodeling and alternative microglia/macrophage activation during recovery. J Neuroinflammation. 2015;12:26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Zents K, Copray S. The therapeutic potential of induced pluripotent stem cells after stroke: evidence from rodent models. Curr Stem Cell Res Ther. 2015;11(2):166–74.

    Article  Google Scholar 

  43. Yin KJ, Olsen K, Hamblin M, Zhang J, Schwendeman SP, Chen YE. Vascular endothelial cell-specific microRNA-15a inhibits angiogenesis in hindlimb ischemia. J Biol Chem. 2012;287(32):27055–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Shanab AY, Elshaer SL, El-Azab MF, Soliman S, Sabbineni H, Matragoon S, et al. Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1). Angiogenesis. 2015;18(2):137–50.

    Article  CAS  PubMed  Google Scholar 

  45. Szpak GM, Lechowicz W, Lewandowska E, Bertrand E, Wierzba-Bobrowicz T, Dymecki J. Border zone neovascularization in cerebral ischemic infarct. Folia Neuropathol. 1999;37(4):264–8.

    CAS  PubMed  Google Scholar 

  46. Wegener S, Gottschalk B, Jovanovic V, Knab R, Fiebach JB, Schellinger PD, et al. Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke. 2004;35(3):616–21.

    Article  PubMed  Google Scholar 

  47. Cobbs CS, Chen J, Greenberg DA, Graham SH. Vascular endothelial growth factor expression in transient focal cerebral ischemia in the rat. Neurosci Lett. 1998;249(2–3):79–82.

    Article  CAS  PubMed  Google Scholar 

  48. Chen HH, Chien CH, Liu HM. Correlation between angiogenesis and basic fibroblast growth factor expression in experimental brain infarct. Stroke. 1994;25(8):1651–7.

    Article  CAS  PubMed  Google Scholar 

  49. Issa R, AlQteishat A, Mitsios N, Saka M, Krupinski J, Tarkowski E, et al. Expression of basic fibroblast growth factor mRNA and protein in the human brain following ischaemic stroke. Angiogenesis. 2005;8(1):53–62.

    Article  CAS  PubMed  Google Scholar 

  50. Iihara K, Sasahara M, Hashimoto N, Hazama F. Induction of platelet-derived growth factor beta-receptor in focal ischemia of rat brain. J Cereb Blood Flow Metab. 1996;16(5):941–9.

    Article  CAS  PubMed  Google Scholar 

  51. Iihara K, Sasahara M, Hashimoto N, Uemura Y, Kikuchi H, Hazama F. Ischemia induces the expression of the platelet-derived growth factor-B chain in neurons and brain macrophages in vivo. J Cereb Blood Flow Metab. 1994;14(5):818–24.

    Article  CAS  PubMed  Google Scholar 

  52. Krupinski J, Kumar P, Kumar S, Kaluza J. Increased expression of TGF-beta 1 in brain tissue after ischemic stroke in humans. Stroke. 1996;27(5):852–7.

    Article  CAS  PubMed  Google Scholar 

  53. Yamashita K, Gerken U, Vogel P, Hossmann K, Wiessner C. Biphasic expression of TGF-beta1 mRNA in the rat brain following permanent occlusion of the middle cerebral artery. Brain Res. 1999;836(1–2):139–45.

    Article  CAS  PubMed  Google Scholar 

  54. Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, et al. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med. 2006;12(4):441–5.

    Article  CAS  PubMed  Google Scholar 

  55. Lin TN, Kim GM, Chen JJ, Cheung WM, He YY, Hsu CY. Differential regulation of thrombospondin-1 and thrombospondin-2 after focal cerebral ischemia/reperfusion. Stroke. 2003;34(1):177–86.

    Article  CAS  PubMed  Google Scholar 

  56. Lin TN, Wang CK, Cheung WM, Hsu CY. Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion. J Cereb Blood Flow Metab. 2000;20(2):387–95.

    Article  CAS  PubMed  Google Scholar 

  57. Zhang Z, Chopp M. Vascular endothelial growth factor and angiopoietins in focal cerebral ischemia. Trends Cardiovasc Med. 2002;12(2):62–6.

    Article  CAS  PubMed  Google Scholar 

  58. Zhang ZG, Chopp M, Lu D, Wayne T, Zhang RL, Morris D. Receptor tyrosine kinase tie 1 mRNA is upregulated on cerebral microvessels after embolic middle cerebral artery occlusion in rat. Brain Res. 1999;847(2):338–42.

    Article  CAS  PubMed  Google Scholar 

  59. Chen J, Zacharek A, Zhang C, Jiang H, Li Y, Roberts C, et al. Endothelial nitric oxide synthase regulates brain-derived neurotrophic factor expression and neurogenesis after stroke in mice. J Neurosci. 2005;25(9):2366–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Huang Z, Huang PL, Ma J, Meng W, Ayata C, Fishman MC, et al. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine. J Cereb Blood Flow Metab. 1996;16(5):981–7.

    Article  CAS  PubMed  Google Scholar 

  61. Chen J, Cui X, Zacharek A, Roberts C, Chopp M. eNOS mediates TO90317 treatment-induced angiogenesis and functional outcome after stroke in mice. Stroke. 2009;40(7):2532–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang ZG, Tsang W, Zhang L, Powers C, Chopp M. Up-regulation of neuropilin-1 in neovasculature after focal cerebral ischemia in the adult rat. J Cereb Blood Flow Metab. 2001;21(5):541–9.

    Article  PubMed  Google Scholar 

  63. Wang S, Olson EN. AngiomiRs—key regulators of angiogenesis. Curr Opin Genet Dev. 2009;19(3):205–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kuehbacher A, Urbich C, Dimmeler S. Targeting microRNA expression to regulate angiogenesis. Trends Pharmacol Sci. 2008;29(1):12–5.

    Article  CAS  PubMed  Google Scholar 

  65. Suarez Y, Sessa WC. MicroRNAs as novel regulators of angiogenesis. Circ Res. 2009;104(4):442–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S. Role of dicer and drosha for endothelial microRNA expression and angiogenesis. Circ Res. 2007;101(1):59–68.

    Article  CAS  PubMed  Google Scholar 

  67. Suarez Y, Fernandez-Hernando C, Yu J, Gerber SA, Harrison KD, Pober JS, et al. Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci U S A. 2008;105(37):14082–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rink C, Khanna S. MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics. 2011;43(10):521–8.

    Article  CAS  PubMed  Google Scholar 

  69. Saugstad JA. MicroRNAs as effectors of brain function with roles in ischemia and injury, neuroprotection, and neurodegeneration. J Cereb Blood Flow Metab. 2010;30(9):1564–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tan JR, Koo YX, Kaur P, Liu F, Armugam A, Wong PT, et al. microRNAs in stroke pathogenesis. Curr Mol Med. 2011;11(2):76–92.

    Article  CAS  PubMed  Google Scholar 

  71. Vemuganti R. The microRNAs and stroke: no need to be coded to be counted. Transl Stroke Res. 2010;1(3):158–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ouyang YB, Stary CM, Yang GY, Giffard R. microRNAs: innovative targets for cerebral ischemia and stroke. Curr Drug Targets. 2013;14(1):90–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Eacker SM, Dawson TM, Dawson VL. The interplay of microRNA and neuronal activity in health and disease. Front Cell Neurosci. 2013;7:136.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Liu XS, Chopp M, Zhang RL, Zhang ZG. MicroRNAs in cerebral ischemia-induced neurogenesis. J Neuropathol Exp Neurol. 2013;72(8):718–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dharap A, Bowen K, Place R, Li LC, Vemuganti R. Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab. 2009;29(4):675–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Jeyaseelan K, Lim KY, Armugam A. MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 2008;39(3):959–66.

    Article  CAS  PubMed  Google Scholar 

  77. Yuan Y, Wang JY, Xu LY, Cai R, Chen Z, Luo BY. MicroRNA expression changes in the hippocampi of rats subjected to global ischemia. J Clin Neurosci. 2010;17(6):774–8.

    Article  CAS  PubMed  Google Scholar 

  78. Liu DZ, Tian Y, Ander BP, Xu H, Stamova BS, Zhan X, et al. Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab. 2010;30(1):92–101.

    Article  PubMed  CAS  Google Scholar 

  79. Lusardi TA, Farr CD, Faulkner CL, Pignataro G, Yang T, Lan J, et al. Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex. J Cereb Blood Flow Metab. 2010;30(4):744–56.

    Article  CAS  PubMed  Google Scholar 

  80. Lee ST, Chu K, Jung KH, Yoon HJ, Jeon D, Kang KM, et al. MicroRNAs induced during ischemic preconditioning. Stroke. 2010;41(8):1646–51.

    Article  PubMed  CAS  Google Scholar 

  81. Dharap A, Vemuganti R. Ischemic pre-conditioning alters cerebral microRNAs that are upstream to neuroprotective signaling pathways. J Neurochem. 2010;113(6):1685–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Tan KS, Armugam A, Sepramaniam S, Lim KY, Setyowati KD, Wang CW, et al. Expression profile of MicroRNAs in young stroke patients. PLoS One. 2009;4(11):e7689.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Gan CS, Wang CW, Tan KS. Circulatory microRNA-145 expression is increased in cerebral ischemia. Genet Mol Res. 2012;11(1):147–52.

    Article  CAS  PubMed  Google Scholar 

  84. Tsai PC, Liao YC, Wang YS, Lin HF, Lin RT, Juo SH. Serum microRNA-21 and microRNA-221 as potential biomarkers for cerebrovascular disease. J Vasc Res. 2013;50(4):346–54.

    Article  CAS  PubMed  Google Scholar 

  85. Yin KJ, Deng Z, Huang H, Hamblin M, Xie C, Zhang J, et al. miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol Dis. 2010;38(1):17–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yin KJ, Deng Z, Hamblin M, Xiang Y, Huang H, Zhang J, et al. Peroxisome proliferator-activated receptor delta regulation of miR-15a in ischemia-induced cerebral vascular endothelial injury. J Neurosci. 2010;30(18):6398–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sepramaniam S, Armugam A, Lim KY, Karolina DS, Swaminathan P, Tan JR, et al. MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J Biol Chem. 2010;285(38):29223–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Buller B, Liu X, Wang X, Zhang RL, Zhang L, Hozeska-Solgot A, et al. MicroRNA-21 protects neurons from ischemic death. FEBS J. 2010;277(20):4299–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Harraz MM, Eacker SM, Wang X, Dawson TM, Dawson VL. MicroRNA-223 is neuroprotective by targeting glutamate receptors. Proc Natl Acad Sci U S A. 2012;109(46):18962–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Siegel C, Li J, Liu F, Benashski SE, McCullough LD. miR-23a regulation of X-linked inhibitor of apoptosis (XIAP) contributes to sex differences in the response to cerebral ischemia. Proc Natl Acad Sci U S A. 2011;108(28):11662–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ouyang YB, Lu Y, Yue S, Xu LJ, Xiong XX, White RE, et al. miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo. Neurobiol Dis. 2012;45(1):555–63.

    Article  CAS  PubMed  Google Scholar 

  92. Moon JM, Xu L, Giffard RG. Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss. J Cereb Blood Flow Metab. 2013;33(12):1976–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Selvamani A, Sathyan P, Miranda RC, Sohrabji F. An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS One. 2012;7(2):e32662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Hunsberger JG, Fessler EB, Wang Z, Elkahloun AG, Chuang DM. Post-insult valproic acid-regulated microRNAs: potential targets for cerebral ischemia. Am J Transl Res. 2012;4(3):316–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Zhang L, Chopp M, Liu X, Teng H, Tang T, Kassis H, et al. Combination therapy with VELCADE and tissue plasminogen activator is neuroprotective in aged rats after stroke and targets MicroRNA-146a and the toll-like receptor signaling pathway. Arterioscler Thromb Vasc Biol. 2012;32(8):1856–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Park HA, Kubicki N, Gnyawali S, Chan YC, Roy S, Khanna S, et al. Natural vitamin E alpha-tocotrienol protects against ischemic stroke by induction of multidrug resistance-associated protein 1. Stroke. 2011;42(8):2308–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Liu XS, Chopp M, Zhang RL, Tao T, Wang XL, Kassis H, et al. MicroRNA profiling in subventricular zone after stroke: MiR-124a regulates proliferation of neural progenitor cells through Notch signaling pathway. PLoS One. 2011;6(8):e23461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Doeppner TR, Doehring M, Bretschneider E, Zechariah A, Kaltwasser B, Muller B, et al. MicroRNA-124 protects against focal cerebral ischemia via mechanisms involving Usp14-dependent REST degradation. Acta Neuropathol. 2013;126(2):251–65.

    Article  CAS  PubMed  Google Scholar 

  99. Xin H, Li Y, Liu Z, Wang X, Shang X, Cui Y, et al. Mir-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells. 2013;31(12):2737–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Pandi G, Nakka VP, Dharap A, Roopra A, Vemuganti R. MicroRNA miR-29c down-regulation leading to de-repression of its target DNA methyltransferase 3a promotes ischemic brain damage. PLoS One. 2013;8(3):e58039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Liu XS, Chopp M, Wang XL, Zhang L, Hozeska-Solgot A, Tang T, et al. MicroRNA-17-92 cluster mediates the proliferation and survival of neural progenitor cells after stroke. J Biol Chem. 2013;288(18):12478–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Li Y, Mao L, Gao Y, Baral S, Zhou Y, Hu B. MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1. Sci Rep. 2015;5:13316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Li LJ, Huang Q, Zhang N, Wang GB, Liu YH. miR-376b-5p regulates angiogenesis in cerebral ischemia. Mol Med Rep. 2014;10(1):527–35.

    CAS  PubMed  Google Scholar 

  104. Lou YL, Guo F, Liu F, Gao FL, Zhang PQ, Niu X, et al. miR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia. Mol Cell Biochem. 2012;370(1–2):45–51.

    Article  CAS  PubMed  Google Scholar 

  105. Zeng L, He X, Wang Y, Tang Y, Zheng C, Cai H, et al. MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain. Gene Ther. 2013;21(1):37–43.

    Article  PubMed  CAS  Google Scholar 

  106. Laterza OF, Lim L, Garrett-Engele PW, Vlasakova K, Muniappa N, Tanaka WK, et al. Plasma microRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem. 2009;55(11):1977–83.

    Article  CAS  PubMed  Google Scholar 

  107. Li M, Zhang J. Circulating microRNAs: potential and emerging biomarkers for diagnosis of cardiovascular and cerebrovascular diseases. Biomed Res Int. 2015;2015:730535.

    PubMed  PubMed Central  Google Scholar 

  108. Zeng L, Liu J, Wang Y, Wang L, Weng S, Tang Y, et al. MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia. Front Biosci (Elite Ed). 2011;3:1265–72.

    Google Scholar 

  109. Cui L, Duchamp NS, Boston DJ, Ren X, Zhang X, Hu H, et al. NF-kappaB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke. Exp Neurol. 2015;263:17–27.

    Article  CAS  PubMed  Google Scholar 

  110. Avraham Y, Davidi N, Lassri V, Vorobiev L, Kabesa M, Dayan M, et al. Leptin induces neuroprotection neurogenesis and angiogenesis after stroke. Curr Neurovasc Res. 2011;8(4):313–22.

    Article  CAS  PubMed  Google Scholar 

  111. Zhang L, Chopp M, Zhang RL, Wang L, Zhang J, Wang Y, et al. Erythropoietin amplifies stroke-induced oligodendrogenesis in the rat. PLoS One. 2010;5(6):e11016.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Lu H, Wang Y, He X, Yuan F, Lin X, Xie B, et al. Netrin-1 hyperexpression in mouse brain promotes angiogenesis and long-term neurological recovery after transient focal ischemia. Stroke. 2012;43(3):838–43.

    Article  CAS  PubMed  Google Scholar 

  113. Doeppner TR, Mlynarczuk-Bialy I, Kuckelkorn U, Kaltwasser B, Herz J, Hasan MR, et al. The novel proteasome inhibitor BSc2118 protects against cerebral ischaemia through HIF1A accumulation and enhanced angioneurogenesis. Brain. 2012;135(Pt 11):3282–97.

    Article  PubMed  Google Scholar 

  114. Wang J, Shi Y, Zhang L, Zhang F, Hu X, Zhang W, et al. Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke. Neurobiol Dis. 2014;68:91–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Zechariah A, ElAli A, Doeppner TR, Jin F, Hasan MR, Helfrich I, et al. Vascular endothelial growth factor promotes pericyte coverage of brain capillaries, improves cerebral blood flow during subsequent focal cerebral ischemia, and preserves the metabolic penumbra. Stroke. 2013;44(6):1690–7.

    Article  CAS  PubMed  Google Scholar 

  116. Soliman S, Ishrat T, Pillai A, Somanath PR, Ergul A, El-Remessy AB, et al. Candesartan induces a prolonged proangiogenic effect and augments endothelium-mediated neuroprotection after oxygen and glucose deprivation: role of vascular endothelial growth factors A and B. J Pharmacol Exp Ther. 2014;349(3):444–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Camos S, Gubern C, Sobrado M, Rodriguez R, Romera VG, Moro MA, et al. The high-mobility group I-Y transcription factor is involved in cerebral ischemia and modulates the expression of angiogenic proteins. Neuroscience. 2014;269:112–30.

    Article  CAS  PubMed  Google Scholar 

  118. Wang L, Chopp M, Teng H, Bolz M, Francisco MA, Aluigi DM, et al. Tumor necrosis factor alpha primes cerebral endothelial cells for erythropoietin-induced angiogenesis. J Cereb Blood Flow Metab. 2011;31(2):640–7.

    Article  CAS  PubMed  Google Scholar 

  119. Shimamura M, Sato N, Oshima K, Aoki M, Kurinami H, Waguri S, et al. Novel therapeutic strategy to treat brain ischemia: overexpression of hepatocyte growth factor gene reduced ischemic injury without cerebral edema in rat model. Circulation. 2004;109(3):424–31.

    Article  CAS  PubMed  Google Scholar 

  120. Jiang N, Finklestein SP, Do T, Caday CG, Charette M, Chopp M. Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat. J Neurol Sci. 1996;139(2):173–9.

    Article  CAS  PubMed  Google Scholar 

  121. Zan L, Zhang X, Xi Y, Wu H, Song Y, Teng G, et al. Src regulates angiogenic factors and vascular permeability after focal cerebral ischemia-reperfusion. Neuroscience. 2014;262:118–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Ma Y, Qiang L, He M. Exercise therapy augments the ischemia-induced proangiogenic state and results in sustained improvement after stroke. Int J Mol Sci. 2013;14(4):8570–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Ding YH, Luan XD, Li J, Rafols JA, Guthinkonda M, Diaz FG, et al. Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke. Curr Neurovasc Res. 2004;1(5):411–20.

    Article  CAS  PubMed  Google Scholar 

  124. Gertz K, Priller J, Kronenberg G, Fink KB, Winter B, Schrock H, et al. Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase-dependent augmentation of neovascularization and cerebral blood flow. Circ Res. 2006;99(10):1132–40.

    Article  CAS  PubMed  Google Scholar 

  125. Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, et al. Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts. Circulation. 2001;104(12 Suppl 1):I207–12.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institutes of Health Grants: NS094930, NS091175, and NS086820 (K.J. Yin).

Author information

Authors and Affiliations

  1. Department of Neurology, University of Pittsburgh School of Medicine, S514 BST, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Ke-Jie Yin M.D., Ph.D. & Xinxin Yang

Authors
  1. Ke-Jie Yin M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinxin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ke-Jie Yin M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Jun Chen

  2. Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    John H. Zhang

  3. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Xiaoming Hu

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Yin, KJ., Yang, X. (2016). Angiogenesis: A Realistic Therapy for Ischemic Stroke. In: Chen, J., Zhang, J., Hu, X. (eds) Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-32337-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-32337-4_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-32335-0

  • Online ISBN: 978-3-319-32337-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation