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Therapeutic Angiogenesis for Brain Ischemia: A Brief Review

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Abstract

In the normal mature brain, blood vessel formation is tightly downregulated. However, pathologic processes such as ischemia can induce cerebral vascular regeneration. Angiogenesis is one of the major styles of new vessel formation. In this article, we summarize the major angiogenic factors in the brain, discuss the significant changes of angiogenic factors and endothelial progenitor cells (EPCs) in response to brain ischemia, and finally, review the therapeutic potential of angiogenic factors and EPCs in experimental cerebral ischemia based on the concept of neurovascular unit.

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References

  • Bacic M, Edwards NA, Merrill MJ (1995) Differential expression of vascular endothelial growth factor (vascular permeability factor) forms in rat tissues. Growth Factors 12:11–15

    PubMed  CAS  Google Scholar 

  • Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP, Gurtner GC (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10:858–864

    Article  PubMed  CAS  Google Scholar 

  • Cunningham LA, Wetzel M, Rosenberg GA (2005) Multiple roles for MMPs and TIMPs in cerebral ischemia. Glia 50:329–339

    Article  PubMed  Google Scholar 

  • Del Zoppo GJ (2006) Stroke and neurovascular protection. N Engl J Med 354:553–555

    Article  PubMed  Google Scholar 

  • Del Zoppo GJ, Mabuchi T (2003) Cerebral microvessel responses to focal ischemia. J Cereb Blood Flow Metab 23:879–894

    Article  PubMed  Google Scholar 

  • Ghani U, Shuaib A, Salam A, Nasir A, Shuaib U, Jeerakathil T, Sher F, O’Rourke F, Nasser AM, Schwindt B, Todd K (2005) Endothelial progenitor cells during cerebrovascular disease. Stroke 36:151–153

    Article  PubMed  Google Scholar 

  • Haas TL (2005) Endothelial cell regulation of matrix metalloproteinases. Can J Physiol Pharmacol 83:1–7

    Article  PubMed  CAS  Google Scholar 

  • Harrigan MR (2003) Angiogenic factors in the central nervous system. Neurosurgery 53:639–660; discussion 660–661

    Article  PubMed  Google Scholar 

  • Hayashi T, Noshita N, Sugawara T, Chan PH (2003) Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab 23:166–180

    Article  PubMed  CAS  Google Scholar 

  • Liew A, Barry F, O’Brien T (2006) Endothelial progenitor cells: diagnostic and therapeutic considerations. Bioessays 28:261–270

    Article  PubMed  Google Scholar 

  • Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60

    Article  PubMed  CAS  Google Scholar 

  • Ohab JJ, Fleming S, Blesch A, Carmichael ST (2006) A neurovascular niche for neurogenesis after stroke. J Neurosci 26:13007–13016

    Article  PubMed  CAS  Google Scholar 

  • Ohta T, Kikuta K, Imamura H, Takagi Y, Nishimura M, Arakawa Y, Hashimoto N, Nozaki K (2006) Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats. Neurosurgery 59:679–686; discussion 679–686

    Article  PubMed  Google Scholar 

  • Red-Horse K, Ferrara N (2006) Imaging tumor angiogenesis. J Clin Invest 116:2585–2587

    Article  PubMed  CAS  Google Scholar 

  • Sbarbati A, Pietra C, Baldassarri AM, Guerrini U, Ziviani L, Reggiani A, Boicelli A, Osculati F (1996) The microvascular system in ischemic cortical lesions. Acta Neuropathol (Berl) 92:56–63

    Article  CAS  Google Scholar 

  • Shen F, Su H, Fan Y, Chen Y, Zhu Y, Liu W, Young WL, Yang GY (2006) Adeno-associated viral-vector-mediated hypoxia-inducible vascular endothelial growth factor gene expression attenuates ischemic brain injury after focal cerebral ischemia in mice. Stroke 37:2601–2606

    Article  PubMed  CAS  Google Scholar 

  • Slevin M, Krupinski J, Slowik A, Kumar P, Szczudlik A, Gaffney J (2000) Serial measurement of vascular endothelial growth factor and transforming growth factor-beta1 in serum of patients with acute ischemic stroke. Stroke 31:1863–1870

    PubMed  CAS  Google Scholar 

  • Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA (2003) VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 111:1843–1851

    Article  PubMed  CAS  Google Scholar 

  • Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T (2004) Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 114:330–338

    Article  PubMed  CAS  Google Scholar 

  • Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD (2000) Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 6:460–463

    Article  PubMed  CAS  Google Scholar 

  • Van Bruggen N, Thibodeaux H, Palmer JT, Lee WP, Fu L, Cairns B, Tumas D, Gerlai R, Williams SP, van Lookeren Campagne M, Ferrara N (1999) VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest 104:1613–1620

    Article  PubMed  Google Scholar 

  • Van Royen N, Hoefer I, Buschmann I, Heil M, Kostin S, Deindl E, Vogel S, Korff T, Augustin H, Bode C, Piek JJ, Schaper W (2002) Exogenous application of transforming growth factor beta 1 stimulates arteriogenesis in the peripheral circulation. FASEB J 16:432–434

    PubMed  Google Scholar 

  • Von Degenfeld G, Banfi A, Springer ML, Blau HM (2003) Myoblast-mediated gene transfer for therapeutic angiogenesis and arteriogenesis. Br J Pharmacol 140:620–626

    Article  CAS  Google Scholar 

  • Wei L, Erinjeri JP, Rovainen CM, Woolsey TA (2001) Collateral growth and angiogenesis around cortical stroke. Stroke 32:2179–2184

    PubMed  CAS  Google Scholar 

  • Weintraub MI (2006) Thrombolysis (tissue plasminogen activator) in stroke: a medicolegal quagmire. Stroke 37:1917–1922

    Article  PubMed  Google Scholar 

  • Yang GY, Xu B, Hashimoto T, Huey M, Chaly T Jr, Wen R, Young WL (2003) Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain. Angiogenesis 6:151–158

    Article  PubMed  CAS  Google Scholar 

  • Yu SW, Friedman B, Cheng Q, Lyden PD (2007) Stroke-evoked angiogenesis results in a transient population of microvessels. J Cereb Blood Flow Metab 27:755–763

    PubMed  Google Scholar 

  • Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, Bruggen N, Chopp M (2000) VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 106:829–838

    PubMed  CAS  Google Scholar 

  • Zhang ZG, Zhang L, Croll SD, Chopp M (2002a) Angiopoietin-1 reduces cerebral blood vessel leakage and ischemic lesion volume after focal cerebral embolic ischemia in mice. Neuroscience 113:683–687

    Article  PubMed  CAS  Google Scholar 

  • Zhang ZG, Zhang L, Jiang Q, Chopp M (2002b) Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res 90:284–288

    Article  PubMed  CAS  Google Scholar 

  • Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, Wang X, Lo EH (2006) Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med 12:441–445

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y, Yang GY, Ahlemeyer B, Pang L, Che XM, Culmsee C, Klumpp S, Krieglstein J (2002) Transforming growth factor-beta 1 increases bad phosphorylation and protects neurons against damage. J Neurosci 22:3898–3909

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesia and Perioperative Care, University of California, San Francisco, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA, 94110, USA

    Yongfeng Fan & Guo-Yuan Yang

  2. Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, 94110, USA

    Guo-Yuan Yang

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  1. Yongfeng Fan
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  2. Guo-Yuan Yang
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Correspondence to Guo-Yuan Yang.

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Fan, Y., Yang, GY. Therapeutic Angiogenesis for Brain Ischemia: A Brief Review. Jrnl Neuroimmune Pharm 2, 284–289 (2007). https://doi.org/10.1007/s11481-007-9073-3

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  • DOI: https://doi.org/10.1007/s11481-007-9073-3

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