This site uses cookies, tags, and tracking settings to store information that help give you the very best browsing experience. Dismiss this warning

Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery

Noboru Kusaka Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Noboru Kusaka in
Current site
Google Scholar
PubMed Close
 M.D.
,
Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Kenji Sugiu in
Current site
Google Scholar
PubMed Close
 M.D.
,
Koji Tokunaga Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Koji Tokunaga in
Current site
Google Scholar
PubMed Close
 M.D.
,
Atsushi Katsumata Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Atsushi Katsumata in
Current site
Google Scholar
PubMed Close
 M.D.
,
Ayumi Nishida Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Ayumi Nishida in
Current site
Google Scholar
PubMed Close
 M.D.
,
Katsunari Namba Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Katsunari Namba in
Current site
Google Scholar
PubMed Close
 M.D.
,
Hirofumi Hamada Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Hirofumi Hamada in
Current site
Google Scholar
PubMed Close
 M.D.
,
Hiroyuki Nakashima Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Hiroyuki Nakashima in
Current site
Google Scholar
PubMed Close
 M.D.
, and
Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama; and Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan

Search for other papers by Isao Date in
Current site
Google Scholar
PubMed Close
 M.D.
Page Range:
882–890
Volume/Issue:
Volume 103: Issue 5
DOI link:
https://doi.org/10.3171/jns.2005.103.5.0882
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $536.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $636.00
Click here for subscription options

  • Purchase Now

    USD  $45.00

  • JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

    USD  $536.00

  • JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

    USD  $636.00
USD  $45.00
USD  $536.00
USD  $636.00
Print or Print + Online Sign in

Object. Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. The conceptual basis for therapeutic angiogenesis after plasmid human VEGF gene (phVEGF) transfer has been established in patients presenting with limb ischemia and myocardial infarction. The authors hypothesized that overexpression of VEGF using a gene transfer method combined with indirect vasoreconstruction might induce effective brain angiogenesis in chronic cerebral hypoperfusion, leading to prevention of ischemic attacks.

Methods. A chronic cerebral hypoperfusion model induced by permanent ligation of both common carotid arteries in rats was used in this investigation. Seven days after induction of cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration in the temporal muscle were performed. Fourteen days after treatment, the VEGF gene therapy group displayed numbers and areas of capillary vessels in temporal muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the control group. In the brain, the number and area of capillary vessels in the group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively, relative to the control group.

Conclusions. In rat models of chronic cerebral hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive surgery significantly increased capillary density in the brain. The authors' results indicate that administration of phVEGF may be an effective therapy in patients with chronic cerebral hypoperfusion, such as those with moyamoya disease.

  • Collapse
  • Expand
Volume 103: Issue 5
Publish Before Print
Volume: 140 (2024)
Show Items
Volume: 139 (2023)
Show Items
Volume: 138 (2023)
Show Items
Volume: 137 (2022)
Show Items
Volume: 136 (2022)
Show Items
Volume: 135 (2021)
Show Items
Volume: 134 (2021)
Show Items
Volume: 133 (2020)
Show Items
Volume: 132 (2020)
Show Items
Volume: 131 (2019)
Show Items
Volume: 130 (2019)
Show Items
Volume: 129 (2018)
Show Items
Volume: 128 (2018)
Show Items
Volume: 127 (2017)
Show Items
Volume: 126 (2017)
Show Items
Volume: 125 (2016)
Show Items
Volume: 124 (2016)
Show Items
Volume: 123 (2015)
Show Items
Volume: 122 (2015)
Show Items
Volume: 121 (2014)
Show Items
Volume: 120 (2014)
Show Items
Volume: 119 (2013)
Show Items
Volume: 118 (2013)
Show Items
Volume: 117 (2012)
Show Items
Volume: 116 (2012)
Show Items
Volume: 115 (2011)
Show Items
Volume: 114 (2011)
Show Items
Volume: 113 (2010)
Show Items
Volume: 112 (2010)
Show Items
Volume: 111 (2009)
Show Items
Volume: 110 (2009)
Show Items
Volume: 109 (2008)
Show Items
Volume: 108 (2008)
Show Items
Volume: 107 (2007)
Show Items
Volume: 106 (2007)
Show Items
Volume: 105 (2006)
Show Items
Volume: 104 (2006)
Show Items
Volume: 103 (2005)
Show Items
Volume: 102 (2005)
Show Items
Volume: 101 (2004)
Show Items
Volume: 100 (2004)
Show Items
Volume: 99 (2003)
Show Items
Volume: 98 (2003)
Show Items
Volume: 97 (2002)
Show Items
Volume: 96 (2002)
Show Items
Volume: 95 (2001)
Show Items
Volume: 94 (2001)
Show Items
Volume: 93 (2000)
Show Items
Volume: 92 (2000)
Show Items
Volume: 91 (1999)
Show Items
Volume: 90 (1999)
Show Items
Volume: 89 (1998)
Show Items
Volume: 88 (1998)
Show Items
Volume: 87 (1997)
Show Items
Volume: 86 (1997)
Show Items
Volume: 85 (1996)
Show Items
Volume: 84 (1996)
Show Items
Volume: 83 (1995)
Show Items
Volume: 82 (1995)
Show Items
Volume: 81 (1994)
Show Items
Volume: 80 (1994)
Show Items
Volume: 79 (1993)
Show Items
Volume: 78 (1993)
Show Items
Volume: 77 (1992)
Show Items
Volume: 76 (1992)
Show Items
Volume: 75 (1991)
Show Items
Volume: 74 (1991)
Show Items
Volume: 73 (1990)
Show Items
Volume: 72 (1990)
Show Items
Volume: 71 (1989)
Show Items
Volume: 70 (1989)
Show Items
Volume: 69 (1988)
Show Items
Volume: 68 (1988)
Show Items
Volume: 67 (1987)
Show Items
Volume: 66 (1987)
Show Items
Volume: 65 (1986)
Show Items
Volume: 64 (1986)
Show Items
Volume: 63 (1985)
Show Items
Volume: 62 (1985)
Show Items
Volume: 61 (1984)
Show Items
Volume: 60 (1984)
Show Items
Volume: 59 (1983)
Show Items
Volume: 58 (1983)
Show Items
Volume: 57 (1982)
Show Items
Volume: 56 (1982)
Show Items
Volume: 55 (1981)
Show Items
Volume: 54 (1981)
Show Items
Volume: 53 (1980)
Show Items
Volume: 52 (1980)
Show Items
Volume: 51 (1979)
Show Items
Volume: 50 (1979)
Show Items
Volume: 49 (1978)
Show Items
Volume: 48 (1978)
Show Items
Volume: 47 (1977)
Show Items
Volume: 46 (1977)
Show Items
Volume: 45 (1976)
Show Items
Volume: 44 (1976)
Show Items
Volume: 43 (1975)
Show Items
Volume: 42 (1975)
Show Items
Volume: 41 (1974)
Show Items
Volume: 40 (1974)
Show Items
Volume: 39 (1973)
Show Items
Volume: 38 (1973)
Show Items
Volume: 37 (1972)
Show Items
Volume: 36 (1972)
Show Items
Volume: 35 (1971)
Show Items
Volume: 34 (1971)
Show Items
Volume: 33 (1970)
Show Items
Volume: 32 (1970)
Show Items
Volume: 31 (1969)
Show Items
Volume: 30 (1969)
Show Items
Volume: 29 (1968)
Show Items
Volume: 28 (1968)
Show Items
Volume: 27 (1967)
Show Items
Volume: 26 (1967)
Show Items
Volume: 25 (1966)
Show Items
Volume: 24 (1966)
Show Items
Volume: 23 (1965)
Show Items
Volume: 22 (1965)
Show Items
Volume: 21 (1964)
Show Items
Volume: 20 (1963)
Show Items
Volume: 19 (1962)
Show Items
Volume: 18 (1961)
Show Items
Volume: 17 (1960)
Show Items
Volume: 16 (1959)
Show Items
Volume: 15 (1958)
Show Items
Volume: 14 (1957)
Show Items
Volume: 13 (1956)
Show Items
Volume: 12 (1955)
Show Items
Volume: 11 (1954)
Show Items
Volume: 10 (1953)
Show Items
Volume: 9 (1952)
Show Items
Volume: 8 (1951)
Show Items
Volume: 7 (1950)
Show Items
Volume: 6 (1949)
Show Items
Volume: 5 (1948)
Show Items
Volume: 4 (1947)
Show Items
Volume: 3 (1946)
Show Items
Volume: 2 (1945)
Show Items
Volume: 1 (1944)
Show Items

Contributor Notes

Address reprint requests to: Kenji Sugiu, M.D., Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2–5–1 Shikata-cho, Okayama 700–8558, Japan. email: ksugiu@md.okayama-u.ac.jp.
  • 1.

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Banai S, , Jaklitsch MT, , Shou M, , Lazarous DF, , Scheinowitz M, & Biro S, et al: Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 89:2183–2189, 1994 Banai S, Jaklitsch MT, Shou M, Lazarous DF, Scheinowitz M, Biro S, et al: Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 89:2183–2189, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Baumgartner I, , Pieczek A, , Manor O, , Blair R, , Kearney M, & Walsh K, et al: Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 97:1114–1123, 1998 Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, et al: Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 97:1114–1123, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Bauters C, , Asahara T, , Zheng LP, , Takeshita S, , Bunting S, & Ferrara N, et al: Recovery of disturbed endothelium-dependent flow in the collateral-perfused rabbit ischemic hindlimb after administration of vascular endothelial growth factor. Circulation 91:2802–2809, 1995 Bauters C, Asahara T, Zheng LP, Takeshita S, Bunting S, Ferrara N, et al: Recovery of disturbed endothelium-dependent flow in the collateral-perfused rabbit ischemic hindlimb after administration of vascular endothelial growth factor. Circulation 91:2802–2809, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Breier G, , Albrecht U, , Sterrer S, & Risau W: Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532, 1992 Breier G, Albrecht U, Sterrer S, Risau W: Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532, 1992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Bruce JN, , Criscuolo GR, , Merrill MJ, , Moquin RR, , Blacklock JB, & Oldfield EH: Vascular permeability induced by protein product of malignant brain tumors: inhibition by dexamethasone. J Neurosurg 67:880–884, 1987 Bruce JN, Criscuolo GR, Merrill MJ, Moquin RR, Blacklock JB, Oldfield EH: Vascular permeability induced by protein product of malignant brain tumors: inhibition by dexamethasone. J Neurosurg 67:880–884, 1987

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Davis HL, , Whalen RG, & Demeneix BA: Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum Gene Ther 4:151–159, 1993 Davis HL, Whalen RG, Demeneix BA: Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum Gene Ther 4:151–159, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Ferrara N, & Davis-Smyth T: The biology of vascular endothelial growth factor. Endocr Rev 18:4–25, 1997 Ferrara N, Davis-Smyth T: The biology of vascular endothelial growth factor. Endocr Rev 18:4–25, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Fishman RA: Steroids in the treatment of brain edema. N Engl J Med 306:359–360, 1982 Fishman RA: Steroids in the treatment of brain edema. N Engl J Med 306:359–360, 1982

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Flamme I, , von Reutern M, , Drexler HC, , Syed-Ali S, & Risau W: Overexpression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation. Dev Biol 171:399–414, 1995 Flamme I, von Reutern M, Drexler HC, Syed-Ali S, Risau W: Overexpression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation. Dev Biol 171:399–414, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Folkman J, & Klagsbrun M: Angiogenic factors. Science 235:442–447, 1987 Folkman J, Klagsbrun M: Angiogenic factors. Science 235:442–447, 1987

  • 12.

    Gale NW, & Yancopoulos GD: Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev 13:1055–1066, 1999 Gale NW, Yancopoulos GD: Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev 13:1055–1066, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    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 18:887–895, 1998 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 18:887–895, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    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 28:2039–2044, 1997 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 28:2039–2044, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Ishikawa T, , Houkin K, , Kamiyama H, & Abe H: Effects of surgical revascularization on outcome of patients with pediatric moyamoya disease. Stroke 28:1170–1173, 1997 Ishikawa T, Houkin K, Kamiyama H, Abe H: Effects of surgical revascularization on outcome of patients with pediatric moyamoya disease. Stroke 28:1170–1173, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Isner JM, , Pieczek A, , Schainfeld R, , Blair R, , Haley L, & Asahara T, et al: Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348:370–374, 1996 Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, et al: Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348:370–374, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Jakeman LB, , Armanini M, , Phillips HS, & Ferrara N: Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 133:848–859, 1993 Jakeman LB, Armanini M, Phillips HS, Ferrara N: Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 133:848–859, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Kinugasa K, , Mandai S, , Kamata I, , Sugiu K, & Ohmoto T: Surgical treatment of moyamoya disease: operative technique for encephalo-duro-arterio-myo-synangiosis, its follow-up, clinical results, and angiograms. Neurosurgery 32:527–531, 1993 Kinugasa K, Mandai S, Kamata I, Sugiu K, Ohmoto T: Surgical treatment of moyamoya disease: operative technique for encephalo-duro-arterio-myo-synangiosis, its follow-up, clinical results, and angiograms. Neurosurgery 32:527–531, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Kinugasa K, , Mandai S, , Tokunaga K, , Kamata I, , Sugiu K, & Handa A, et al: Ribbon encephalo-duro-arterio-myo-synangiosis for moyamoya disease. Surg Neurol 41:455–461, 1994 Kinugasa K, Mandai S, Tokunaga K, Kamata I, Sugiu K, Handa A, et al: Ribbon encephalo-duro-arterio-myo-synangiosis for moyamoya disease. Surg Neurol 41:455–461, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Kovacs Z, , Ikezaki K, , Samoto K, , Inamura T, & Fukui M: VEGF and flt. Expression time kinetics in rat brain infarct. Stroke 27:1865–1873, 1996 Kovacs Z, Ikezaki K, Samoto K, Inamura T, Fukui M: VEGF and flt. Expression time kinetics in rat brain infarct. Stroke 27:1865–1873, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Krupinski J, , Issa R, , Bujny T, , Slevin M, , Kumar P, & Kumar S, et al: A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans. Stroke 28:564–573, 1997 Krupinski J, Issa R, Bujny T, Slevin M, Kumar P, Kumar S, et al: A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans. Stroke 28:564–573, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Leung DW, , Cachianes G, , Kuang WJ, , Goeddel DV, & Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309, 1989 Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309, 1989

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Levy MY, , Barron LG, , Meyer KB, & Szoka FC Jr: Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Ther 3:201–211, 1996 Levy MY, Barron LG, Meyer KB, Szoka FC Jr: Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Ther 3:201–211, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Losordo DW, , Vale PR, , Symes JF, , Dunnington CH, , Esakof DD, & Maysky M, et al: Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98:2800–2804, 1998 Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, et al: Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98:2800–2804, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Manthorpe M, , Cornefert-Jensen F, , Hartikka J, , Felgner J, , Rundell A, & Margalith M, et al: Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum Gene Ther 4:419–431, 1993 Manthorpe M, Cornefert-Jensen F, Hartikka J, Felgner J, Rundell A, Margalith M, et al: Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum Gene Ther 4:419–431, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Marti HH, & Risau W: Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci USA 95:15809–15814, 1998 Marti HH, Risau W: Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci USA 95:15809–15814, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Matsushima T, , Inoue T, , Suzuki SO, , Fujii K, , Fukui M, & Hasuo K: Surgical treatment of moyamoya disease in pediatric patients—comparison between the results of indirect and direct revascularization procedures. Neurosurgery 31:401–405, 1992 Matsushima T, Inoue T, Suzuki SO, Fujii K, Fukui M, Hasuo K: Surgical treatment of moyamoya disease in pediatric patients—comparison between the results of indirect and direct revascularization procedures. Neurosurgery 31:401–405, 1992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Millauer B, , Wizigmann-Voos S, , Schnurch H, , Martinez R, , Moller NP, & Risau W, et al: High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72:835–846, 1993 Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Moller NP, Risau W, et al: High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72:835–846, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Miyoshi Y, , Date I, & Ohmoto T: Three-dimensional morphological study of microvascular regeneration in cavity wall of the rat cerebral cortex using the scanning electron microscope: implications for delayed neural grafting into brain cavities. Exp Neurol 131:69–82, 1995 Miyoshi Y, Date I, Ohmoto T: Three-dimensional morphological study of microvascular regeneration in cavity wall of the rat cerebral cortex using the scanning electron microscope: implications for delayed neural grafting into brain cavities. Exp Neurol 131:69–82, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Monacci WT, , Merrill MJ, & Oldfield EH: Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol 264:995–1002, 1993 Monacci WT, Merrill MJ, Oldfield EH: Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol 264:995–1002, 1993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Ni JW, , Ohta H, , Matsumoto K, & Watanabe H: Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res 653:231–236, 1994 Ni JW, Ohta H, Matsumoto K, Watanabe H: Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res 653:231–236, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Ogunshola OO, , Stewart WB, , Mihalcik V, , Solli T, , Madri JA, & Ment LR: Neuronal VEGF expression correlates with angiogenesis in postnatal developing rat brain. Brain Res Dev Brain Res 119:139–153, 2000 Ogunshola OO, Stewart WB, Mihalcik V, Solli T, Madri JA, Ment LR: Neuronal VEGF expression correlates with angiogenesis in postnatal developing rat brain. Brain Res Dev Brain Res 119:139–153, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Ohta H, , Nishikawa H, , Kimura H, , Anayama H, & Miyamoto M: Chronic cerebral hypoperfusion by permanent internal carotid ligation produces learning impairment without brain damage in rats. Neuroscience 79:1039–1050, 1997 Ohta H, Nishikawa H, Kimura H, Anayama H, Miyamoto M: Chronic cerebral hypoperfusion by permanent internal carotid ligation produces learning impairment without brain damage in rats. Neuroscience 79:1039–1050, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Park JE, , Chen HH, , Winer J, , Houck KA, & Ferrara N: Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 269:25646–25654, 1994 Park JE, Chen HH, Winer J, Houck KA, Ferrara N: Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 269:25646–25654, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Rosenstein JM, , Mani N, , Silverman WF, & Krum JM: Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo. Proc Natl Acad Sci USA 95:7086–7091, 1998 Rosenstein JM, Mani N, Silverman WF, Krum JM: Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo. Proc Natl Acad Sci USA 95:7086–7091, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Schratzberger P, , Schratzberger G, , Silver M, , Curry C, , Kearney M, & Magner M, et al: Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy. Nat Med 6:405–413, 2000 Schratzberger P, Schratzberger G, Silver M, Curry C, Kearney M, Magner M, et al: Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy. Nat Med 6:405–413, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Shweiki D, , Itin A, , Soffer D, & Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845, 1992 Shweiki D, Itin A, Soffer D, Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845, 1992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Sondell M, , Lundborg G, & Kanje M: Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J Neurosci 19:5731–5740, 1999 Sondell M, Lundborg G, Kanje M: Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J Neurosci 19:5731–5740, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Stratford-Perricaudet LD, , Makeh I, , Perricaudet M, & Briand P: Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest 90:626–630, 1992 Stratford-Perricaudet LD, Makeh I, Perricaudet M, Briand P: Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest 90:626–630, 1992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Stroemer RP, , Kent TA, & Hulsebosch CE: Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. Stroke 29:2381–2395, 1998 Stroemer RP, Kent TA, Hulsebosch CE: Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. Stroke 29:2381–2395, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Symes JF, , Losordo DW, , Vale PR, , Lathi KG, , Esakof DD, & Mayskiy M, et al: Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann Thorac Surg 68:830–837, 1999 Symes JF, Losordo DW, Vale PR, Lathi KG, Esakof DD, Mayskiy M, et al: Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann Thorac Surg 68:830–837, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Takeshita S, , Isshiki T, & Sato T: Increased expression of direct gene transfer into skeletal muscles observed after acute ischemic injury in rats. Lab Invest 74:1061–1065, 1996 Takeshita S, Isshiki T, Sato T: Increased expression of direct gene transfer into skeletal muscles observed after acute ischemic injury in rats. Lab Invest 74:1061–1065, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Takeshita S, , Pu LQ, , Stein LA, , Sniderman AD, , Bunting S, & Ferrara N, et al: Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia. Circulation 90:II228–II234, 1994 Takeshita S, Pu LQ, Stein LA, Sniderman AD, Bunting S, Ferrara N, et al: Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia. Circulation 90:II228–II234, 1994

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Takeshita S, , Tsurumi Y, , Couffinahl T, , Asahara T, , Bauters C, & Symes J, et al: Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest 75:487–501, 1996 Takeshita S, Tsurumi Y, Couffinahl T, Asahara T, Bauters C, Symes J, et al: Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest 75:487–501, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Takeshita S, , Weir L, , Chen D, , Zheng LP, , Riessen R, & Bauters C, et al: Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 227:628–635, 1996 Takeshita S, Weir L, Chen D, Zheng LP, Riessen R, Bauters C, et al: Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 227:628–635, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Takeshita S, , Zheng LP, , Brogi E, , Kearney M, , Pu LQ, & Bunting S, et al: Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 93:662–670, 1994 Takeshita S, Zheng LP, Brogi E, Kearney M, Pu LQ, Bunting S, et al: Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 93:662–670, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Tanaka K, , Ogawa N, , Asanuma M, , Kondo Y, & Nomura M: Relationship between cholinergic dysfunction and discrimination learning disabilities in Wistar rats following chronic cerebral hypoperfusion. Brain Res 729:55–65, 1996 Tanaka K, Ogawa N, Asanuma M, Kondo Y, Nomura M: Relationship between cholinergic dysfunction and discrimination learning disabilities in Wistar rats following chronic cerebral hypoperfusion. Brain Res 729:55–65, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Tanaka K, , Wada N, , Hori K, , Asanuma M, , Nomura M, & Ogawa N: Chronic cerebral hypoperfusion disrupts discriminative behavior in acquired-learning rats. J Neurosci Methods 84:63–68, 1998 Tanaka K, Wada N, Hori K, Asanuma M, Nomura M, Ogawa N: Chronic cerebral hypoperfusion disrupts discriminative behavior in acquired-learning rats. J Neurosci Methods 84:63–68, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Tripathy SK, , Svensson EC, , Black HB, , Goldwasser E, , Margalith M, & Hobart PM, et al: Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector. Proc Natl Acad Sci USA 93:10876–10880, 1996 Tripathy SK, Svensson EC, Black HB, Goldwasser E, Margalith M, Hobart PM, et al: Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector. Proc Natl Acad Sci USA 93:10876–10880, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Tsuchiya M, , Sako K, , Yura S, & Yonemasu Y: Local cerebral glucose utilization following acute and chronic bilateral carotid artery ligation in Wistar rats: relation to changes in local cerebral blood flow. Expl Brain Res 95:1–7, 1993 Tsuchiya M, Sako K, Yura S, Yonemasu Y: Local cerebral glucose utilization following acute and chronic bilateral carotid artery ligation in Wistar rats: relation to changes in local cerebral blood flow. Expl Brain Res 95:1–7, 1993

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Tsurumi Y, , Takeshita S, , Chen D, , Kearney M, , Rossow ST, & Passeri J, et al: Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. Circulation 94:3281–3290, 1996 Tsurumi Y, Takeshita S, Chen D, Kearney M, Rossow ST, Passeri J, et al: Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. Circulation 94:3281–3290, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Wakita H, , Tomimoto H, , Akiguchi I, & Kimura J: Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunohistochemical study. Acta Neuropath 87:484–492, 1994 Wakita H, Tomimoto H, Akiguchi I, Kimura J: Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunohistochemical study. Acta Neuropath 87:484–492, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Wakita H, , Tomimoto H, , Akiguchi I, & Kimura J: Protective effect of cyclosporine A on white matter changes in the rat brain after chronic cerebral hypoperfusion. Stroke 26:1415–1422, 1995 Wakita H, Tomimoto H, Akiguchi I, Kimura J: Protective effect of cyclosporine A on white matter changes in the rat brain after chronic cerebral hypoperfusion. Stroke 26:1415–1422, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    Wang W, , Merrill MJ, & Borchardt RT: Vascular endothelial growth factor affects permeability of brain microvessel endothelial cells in vitro. Am J Physiol 271:1973–1980, 1996 Wang W, Merrill MJ, Borchardt RT: Vascular endothelial growth factor affects permeability of brain microvessel endothelial cells in vitro. Am J Physiol 271:1973–1980, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    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 106:829–838, 2000 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 106:829–838, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 1312 89 9
Full Text Views 193 15 3
PDF Downloads 153 15 3
EPUB Downloads 0 0 0