Targeting Microvasculature for Neuroprotection after SCI

Neurotherapeutics

Volumn 8, Issue 2, 2011, Pages 240-251

  Fassbender, Janelle M ^a   Whittemore, Scott R ^a   Hagg, Theo ^a  

^a University of Louisville School of Medicine   (United States)

Author keywords

inflammation; neuroprotection; Spinal cord injury; therapeutics; vasculature

Indexed keywords

4 AMINOPYRIDINE; ADENOVIRUS VECTOR; ADRENALIN; ANGIOPOIETIN 1; ANGIOPOIETIN 2; BILIVERDIN; C 16; GANGLIOSIDE GM1; GLIBENCLAMIDE; HEMIN; HYPERTENSIVE FACTOR; MATRIX METALLOPROTEINASE 14; METHYLPREDNISOLONE; NALOXONE; NEUROPROTECTIVE AGENT; NIMODIPINE; REACTIVE OXYGEN METABOLITE; REPAGLINIDE; SCATTER FACTOR; SELENIUM; SM 216289; TEMPOL; TIRILAZAD; TIZANIDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN A; VITRONECTIN RECEPTOR; YELLOW FLUORESCENT PROTEIN; ZINC FINGER PROTEIN;

ANGIOGENESIS; ANTISENSE THERAPY; BLOOD SPINAL CORD BARRIER; BLOOD VESSEL PERMEABILITY; CELL THERAPY; COMPETITIVE INHIBITION; DRUG EFFICACY; ENDOTHELIUM CELL; EXPERIMENTAL STUDY; EXTRACELLULAR MATRIX; GENE LOCUS; GENETIC MODEL; GLYCOCALYX; GRAY MATTER; HUMAN; LEUKOENCEPHALOPATHY; LIPID PEROXIDATION; MEAN ARTERIAL PRESSURE; MEMBRANE PERMEABILITY; MICROVASCULATURE; NEURAL STEM CELL TRANSPLANTATION; NEUROPROTECTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OLIGODENDROGLIA; OXIDATIVE STRESS; PARACRINE SIGNALING; PATHOPHYSIOLOGY; PHASE 3 CLINICAL TRIAL (TOPIC); PORPHYRIA; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; SPINAL CORD BLOOD FLOW; SPINAL CORD COMPRESSION; SPINAL CORD INJURY; TRAUMATIC BRAIN INJURY; UMBILICAL VEIN ENDOTHELIAL CELL; UPREGULATION; VIRAL GENE DELIVERY SYSTEM;

ANIMALS; CEREBROVASCULAR CIRCULATION; HUMANS; MICROVESSELS; NEOVASCULARIZATION, PHYSIOLOGIC; NERVE DEGENERATION; NEUROPROTECTIVE AGENTS; SPINAL CORD INJURIES;

EID: 79955063410     PISSN: 19337213     EISSN: None     Source Type: Journal    
DOI: 10.1007/s13311-011-0029-1     Document Type: Review

References (164)

1. Allen A. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column. A preliminary report. JAMA 1911; 57: 878-880.
2. Popovich P, McTigue D. Damage control in the nervous system: beware the immune system in spinal cord injury. Nat Med 2009; 15: 736-737.
3. Mautes AE, Weinzierl MR, Donovan F, Noble LJ. Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther 2000; 80: 673-687.
4. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991; 75: 15-26.
5. Hagg T, Oudega M. Degenerative and spontaneous regenerative processes after spinal cord injury. J Neurotrauma 2006; 23: 264-280.
6. Hall ED, Springer JE. Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx 2004; 1: 80-100.
7. Bramlett HM, Dietrich WD. Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res 2007; 161: 125-141.
8. Alexander JK, Popovich PG. Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration. Prog Brain Res 2009; 175: 125-137.
9. Allen AR. Remarks on the histopathological changes in the spinal cord due to impact. An experimental study. J. Nerv. Ment. Dis 1914; 41: 141-147.
10. Schneider RC, Crosby EC. Vascular insufficiency of brain stem and spinal cord in spinal trauma. Neurology 1959; 9: 643-656.
11. Tonnis D. [Spinal cord trauma and circulatory insufficiency. Studies on the pathogenesis of traumatic spinal cord lesions and the symptoms of insufficiency of spinal circulation]. Beitr Neurochir 1963; 5: 1-167.
12. Wolman L. The disturbance of circulation in traumatic paraplegia in acute and late stages: a pathological study. Paraplegia 1965; 2: 213-226.
13. Kamiya T. Experimental study on anterior spinal cord compression with special emphasis on vascular disturbance. Nagoya J Med Sci 1968; 31: 171-190.
14. Wagner FC Jr., van Gilder JC, Dohrmann GJ. The development of intramedullary cavitation following spinal cord injury: an experimental pathological study. Paraplegia 1977; 14: 245-250.
15. Means ED, Anderson DK, Nicolosi G, Gaudsmith J. Microvascular perfusion experimental spinal cord injury. Surg Neurol 1978; 9: 353-360.
16. Zhang Z, Krebs CJ, Guth L. Experimental analysis of progressive necrosis after spinal cord trauma in the rat: etiological role of the inflammatory response. Exp Neurol 1997; 143: 141-152.
17. Loy DN, Crawford CH, Darnall JB, Burke DA, Onifer SM, Whittemore SR. Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat. J Comp Neurol 2002; 445: 308-324.
18. Facchiano F, Fernandez E, Mancarella S, et al. Promotion of regeneration of corticospinal tract axons in rats with recombinant vascular endothelial growth factor alone and combined with adenovirus coding for this factor. J Neurosurg 2002; 97: 161-168.
19. Goldsmith HS. The evolution of omentum transposition: from lymphedema to spinal cord, stroke and Alzheimer's disease. Neurol Res 2004; 26: 586-593.
20. Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. J Neurotrauma 2004; 21: 429-440.
21. Fleming JC, Norenberg MD, Ramsay DA, et al. The cellular inflammatory response in human spinal cords after injury. Brain 2006; 129(Pt 12): 3249-3269.
22. Tator CH. Review of experimental spinal cord injury with emphasis on the local and systemic circulatory effects. Neurochirurgie 1991; 37: 291-302.
23. Noble LJ, Wrathall JR. Correlative analyses of lesion development and functional status after graded spinal cord contusive injuries in the rat. Exp Neurol 1989; 103: 34-40.
24. Beggs JL, Waggener JD. The acute microvascular responses to spinal cord injury. Adv Neurol 1979; 22: 179-189.
25. Sadrzadeh SM, Anderson DK, Panter SS, Hallaway PE, Eaton JW. Hemoglobin potentiates central nervous system damage. J Clin Invest 1987; 79: 662-664.
26. Anthes DL, Theriault E, Tator CH. Ultrastructural evidence for arteriolar vasospasm after spinal cord trauma. Neurosurgery 1996; 39: 804-814.
27. Smith AJ, McCreery DB, Bloedel JR, Chou SN. Hyperemia, CO2 responsiveness, and autoregulation in the white matter following experimental spinal cord injury. J Neurosurg 1978; 48: 239-251.
28. Senter HJ, Venes JL. Loss of autoregulation and posttraumatic ischemia following experimental spinal cord trauma. J Neurosurg 1979; 50: 198-206.
29. Bingham WG, Goldman H, Friedman SJ, Murphy S, Yashon D, Hunt WE. Blood flow in normal and injured monkey spinal cord. J Neurosurg 1975; 43: 162-171.
30. Guha A, Tator CH, Smith CR, Piper I. Improvement in post-traumatic spinal cord blood flow with a combination of a calcium channel blocker and a vasopressor. J Trauma 1989; 29: 1440-1447.
31. Vale FL, Burns J, Jackson AB, Hadley MN. Combined medical and surgical treatment after acute spinal cord injury: results of a prospective pilot study to assess the merits of aggressive medical resuscitation and blood pressure management. J Neurosurg 1997; 87: 239-246.
32. Guth L, Zhang Z, Steward O. The unique histopathological responses of the injured spinal cord. Implications for neuroprotective therapy. Ann N Y Acad Sci 1999; 890: 366-384.
33. Griffiths IR, Burns N, Crawford AR. Early vascular changes in the spinal grey matter following impact injury. Acta Neuropathol 1978; 41: 33-39.
34. Casella GT, Bunge MB, Wood PM. Endothelial cell loss is not a major cause of neuronal and glial cell death following contusion injury of the spinal cord. Exp Neurol 2006; 202: 8-20.
35. Dohrmann GJ, Wick KM. Demonstration of the microvasculature of the spinal cord by intravenous injection of the fluorescent dye, thioflavine S. Stain Technol 1971; 46: 321-322.
36. Whetstone WD, Hsu JY, Eisenberg M, Werb Z, Noble-Haeusslein LJ. Blood-spinal cord barrier after spinal cord injury: relation to revascularization and wound healing. J Neurosci Res 2003; 74: 227-239.
37. Benton RL, Maddie MA, Minnillo DR, Hagg T, Whittemore SR. Griffonia simplicifolia isolectin B4 identifies a specific subpopulation of angiogenic blood vessels following contusive spinal cord injury in the adult mouse. J Comp Neurol 2008; 507: 1031-1052.
38. Koyanagi I, Tator CH, Lea PJ. Three-dimensional analysis of the vascular system in the rat spinal cord with scanning electron microscopy of vascular corrosion casts. Part 2: Acute spinal cord injury. Neurosurgery 1993; 33: 285-291.
39. Casella GT, Marcillo A, Bunge MB, Wood PM. New vascular tissue rapidly replaces neural parenchyma and vessels destroyed by a contusion injury to the rat spinal cord. Exp Neurol 2002; 173: 63-76.
40. Hall ED. Inhibition of lipid peroxidation in central nervous system trauma and ischemia. J Neurol Sci 1995; 134(suppl): 79-83.
41. Whalley K, O'Neill P, Ferretti P. Changes in response to spinal cord injury with development: vascularization, hemorrhage and apoptosis. Neuroscience 2006; 137: 821-832.
42. Lin Y, Vreman HJ, Wong RJ, Tjoa T, Yamauchi T, Noble-Haeusslein LJ. Heme oxygenase-1 stabilizes the blood-spinal cord barrier and limits oxidative stress and white matter damage in the acutely injured murine spinal cord. J Cereb Blood Flow Metab 2007; 27: 1010-1021.
43. Hall ED, Braughler JM. Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review. Cent Nerv Syst Trauma 1986; 3: 281-294.
44. Demopoulos HB, Flamm ES, Seligman ML, Pietronigro DD, Tomasula J, DeCrescito V. Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury. Can J Physiol Pharmacol 1982; 60: 1415-1424.
45. Giancotti FG, Ruoslahti E. Integrin signaling. Science 1999; 285: 1028-1032.
46. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992; 69: 11-25.
47. Goodman JH, Bingham WG Jr., Hunt WE. Platelet aggregation in experimental spinal cord injury. Ultrastructural observations. ArchNeurol 1979; 36: 197-201.
48. Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 1994; 264: 569-571.
49. Ritz MF, Graumann U, Gutierrez B, Hausmann O. Traumatic spinal cord injury alters angiogenic factors and TGF-beta1 that may affect vascular recovery. Curr Neurovasc Res 2010; 7: 301-310.
50. Mochizuki N. Vascular integrity mediated by vascular endothelial cadherin and regulated by sphingosine 1-phosphate and angiopoietin-1. Circ J 2009; 73: 2183-2191.
51. Nambu H, Nambu R, Oshima Y, et al. Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier. Gene Ther 2004; 11: 865-873.
52. Carmeliet P. Angiogenesis in health and disease. Nat Med 2003; 9: 653-660.
53. Zhang ZG, Zhang L, Croll SD, Chopp M. Angiopoietin-1 reduces cerebral blood vessel leakage and ischemic lesion volume after focal cerebral embolic ischemia in mice. Neuroscience 2002; 113: 683-687.
54. Uemura A, Ogawa M, Hirashima M, et al. Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells. J Clin Invest 2002; 110: 1619-1628.
55. Gale NW, Thurston G, Davis S, et al. Complementary and coordinated roles of the VEGFs and angiopoietins during normal and pathologic vascular formation. Cold Spring Harb Symp Quant Biol 2002; 67: 267-273.
56. Thurston G, Wang Q, Baffert F, et al. Angiopoietin 1 causes vessel enlargement, without angiogenic sprouting, during a critical developmental period. Development 2005; 132: 3317-3326.
57. Thurston G, Rudge JS, Ioffe E, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. NatMed 2000; 6: 460-463.
58. Thurston G, Suri C, Smith K, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 1999; 286: 2511-2514.
59. Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA 2002; 99: 11205-11210.
60. Beggs JL, Waggener JD. Microvascular regeneration following spinal cord injury: the growth sequence and permeability properties of new vessels. Adv Neurol 1979; 22: 191-206.
61. Noble LJ, Mautes AE, Hall JJ. Characterization of the microvascular glycocalyx in normal and injured spinal cord in the rat. J Comp Neurol 1996; 376: 542-556.
62. Popovich PG, Horner PJ, Mullin BB, Stokes BT. A quantitative spatial analysis of the blood-spinal cord barrier. I. Permeability changes after experimental spinal contusion injury. Exp Neurol 1996; 142: 258-275.
63. del Zoppo GJ. Inflammationd and the neurovascular unit in the setting of focal cerebral ischemia. Neuroscience 2009; 158: 972-982.
64. Guo S, Kim WJ, Lok J, et al. Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc Natl Acad Sci U S A 2008; 105: 7582-7587.
65. Dore-Duffy P. Pericytes: pluripotent cells of the blood brain barrier. Curr Pharm Des 2008; 14: 1581-1593.
66. Bell RD, Winkler EA, Sagare AP, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 2010; 68: 409-427.
67. Armulik A, Genove G, Mae M, et al. Pericytes regulate the blood-brain barrier. Nature 2010; 468: 557-561.
68. Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010; 468: 562-566.
69. Dore-Duffy P, Owen C, Balabanov R, Murphy S, Beaumont T, Rafols JA. Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc Res 2000; 60: 55-69.
70. del Zoppo GJ. The neurovascular unit in the setting of stroke. J Intern Med 2010; 267: 156-171.
71. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37: 13-25.
72. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 2004; 84: 869-901.
73. Willis CL, Leach L, Clarke GJ, Nolan CC, Ray DE. Reversible disruption of tight junction complexes in the rat blood-brain barrier, following transitory focal astrocyte loss. Glia 2004; 48: 1-13.
74. Smith R, Brown EH, Shum-Siu A, et al. Swim training initiated acutely after spinal cord injury is ineffective and induces extravasation in and around the epicenter. J Neurotrauma 2009; 26: 1017-1027.
75. Noble LJ, Donovan F, Igarashi T, Goussev S, Werb Z. Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. J Neurosci 2002; 22: 7526-7535.
76. Noble LJ, Wrathall JR. Distribution and time course of protein extravasation in the rat spinal cord after contusive injury. Brain Res 1989; 482: 57-66.
77. Nagy Z, Peters H, Huttner I. Endothelial surface charge: blood-brain barrier opening to horseradish peroxidase induced by the polycation protamin sulfate. Acta Neuropathol Suppl 1981; 7: 7-9.
78. Nagy Z, Peters H, Huttner I. Charge-related alterations of the cerebral endothelium. Lab Invest 1983; 49: 662-671.
79. Mozer AB, Whittemore SR, Benton RL. Spinal microvascular expression of PV-1 is associated with inflammation, perivascular astrocyte loss, and diminished EC glucose transport potential in acute SCI. Curr Neurovasc Res 2010; 7: 238-250.
80. Furlan JC, Noonan V, Cadotte DW, Fehlings MG. Timing of decompressive surgery of spinal cord after traumatic spinal cord injury: an evidence-based examination of pre-clinical and clinical studies. J Neurotrauma 2010; 27: 1-29.
81. Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 1996; 139: 244-256.
82. Casha S, Yu WR, Fehlings MG. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 2001; 103: 203-218.
83. Han S, Arnold SA, Sithu SD, et al. Rescuing vasculature with intravenous angiopoietin-1 and alpha v beta 3 integrin peptide is protective after spinal cord injury. Brain 2010; 133(Pt 4): 1026-1042.
84. Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol 2008; 209: 378-388.
85. Takigawa T, Yonezawa T, Yoshitaka T, et al. Separation of the perivascular basement membrane provides a conduit for inflammatory cells in a mouse spinal cord injury model. J Neurotrauma 2010; 27: 739-751.
86. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2004; 24: 2143-2155.
87. Voskuhl RR, Peterson RS, Song B, et al. Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 2009; 29: 11511-11522.
88. Okada S, Nakamura M, Katoh H, et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 2006; 12: 829-834.
89. Onose G, Anghelescu A, Muresanu DF, et al. A review of published reports on neuroprotection in spinal cord injury. Spinal Cord 2009; 47: 716-726.
90. Hurlbert RJ, Hamilton MG. Methylprednisolone for acute spinal cord injury: 5-year practice reversal. Can J Neurol Sci 2008; 35: 41-45.
91. Fehlings MG, Tator CH, Linden RD. The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury. J Neurosurg 1989; 71: 403-416.
92. Ross IB, Tator CH, Theriault E. Effect of nimodipine or methylprednisolone on recovery from acute experimental spinal cord injury in rats. Surg Neurol 1993; 40: 461-470.
93. Hall ED, Wolf DL. A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia. J Neurosurg 1986; 64: 951-961.
94. Hall ED. Effects of the 21-aminosteroid U74006F on posttraumatic spinal cord ischemia in cats. J Neurosurg 1988; 68: 462-465.
95. Hall ED, McCall JM, Means ED. Therapeutic potential of the lazaroids (21-aminosteroids) in acute central nervous system trauma, ischemia and subarachnoid hemorrhage. Adv Pharmacol 1994; 28: 221-268.
96. Yamauchi T, Lin Y, Sharp FR, Noble-Haeusslein LJ. Hemin induces heme oxygenase-1 in spinal cord vasculature and attenuates barrier disruption and neutrophil infiltration in the injured murine spinal cord. J Neurotrauma 2004; 21: 1017-1030.
97. Simard JM, Woo SK, Norenberg MD, et al. Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma. Sci Transl Med 2010; 2: 28ra29.
98. Simard JM, Tsymbalyuk O, Ivanov A, et al. Endothelial sulfonylurea receptor 1-regulated NC Ca-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury. J Clin Invest 2007; 117: 2105-2113.
99. Gerzanich V, Woo SK, Vennekens R, et al. De novo expression of Trpm4 initiates secondary hemorrhage in spinal cord injury. Nat Med 2009; 15: 185-191.
100. Herrera JJ, Sundberg LM, Zentilin L, Giacca M, Narayana PA. Sustained expression of vascular endothelial growth factor and angiopoietin-1 improves blood spinal cord barrier integrity and functional recovery after spinal cord injury. J Neurotrauma 2010; 27: 2067-2076.
101. Nakashima S, Arnold SA, Mahoney ET, et al. Small-molecule protein tyrosine phosphatase inhibition as a neuroprotective treatment after spinal cord injury in adult rats. J Neurosci 2008; 28: 7293-7303.
102. Liu Y, Figley S, Spratt SK, et al. An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury. Neurobiol Dis 2010; 37: 384-393.
103. Kim HM, Hwang DH, Lee JE, Kim SU, Kim BG. Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. PLoS One 2009; 4: e4987.
104. Kaneko S, Iwanami A, Nakamura M, et al. A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med 2006; 12: 1380-1389.
105. Fassbender JM, Myers SA, Whittemore SR. Activating Notch signaling post-SCI modulates angiogenesis in penumbral vascular beds but does not improve hindlimb locomotor recovery. Exp Neurol 2011; 227: 302-313.
106. Kitamura K, Iwanami A, Nakamura M, et al. Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury. J Neurosci Res 2007; 85: 2332-2342.
107. Sasaki H, Ishikawa M, Tanaka N, et al. Administration of human peripheral blood-derived CD133+ cells accelerates functional recovery in a rat spinal cord injury model. Spine (Phila Pa 1976) 2009; 34: 249-254.
108. Glaser J, Gonzalez R, Perreau VM, Cotman CW, Keirstead HS. Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury. J Neurosci Res 2004; 77: 701-708.
109. Hall ED, Braughler JM, McCall JM. New pharmacological treatment of acute spinal cord trauma. J Neurotrauma 1988; 5: 81-89.
110. Xiong Y, Hall ED. Pharmacological evidence for a role of peroxynitrite in the pathophysiology of spinal cord injury. Exp Neurol 2009; 216: 105-114.
111. Liu XM, Peyton KJ, Ensenat D, et al. Endoplasmic reticulum stress stimulates heme oxygenase-1 gene expression in vascular smooth muscle. Role in cell survival. J Biol Chem 2005; 280: 872-877.
112. Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996; 87: 1171-1180.
113. Dumont DJ, Gradwohl GJ, Fong GH, Auerbach R, Breitman ML. The endothelial-specific receptor tyrosine kinase, tek, is a member of a new subfamily of receptors. Oncogene 1993; 8: 1293-1301.
114. Harfouche R, Hassessian HM, Guo Y, et al. Mechanisms which mediate the antiapoptotic effects of angiopoietin-1 on endothelial cells. Microvasc Res 2002; 64: 135-147.
115. Fujikawa K, de de Aos Scherpenseel I, Jain SK, Presman E, Christensen RA, Varticovski L. Role of PI 3-kinase in angiopoietin-1-mediated migration and attachment-dependent survival of endothelial cells. Exp Cell Res 1999; 253: 663-672.
116. Kim I, Moon SO, Park SK, Chae SW, Koh GY. Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression. Circ Res 2001; 89: 477-479.
117. Eliceiri BP. Integrin and growth factor receptor crosstalk. Circ Res 2001; 89: 1104-1110.
118. DeBusk LM, Hallahan DE, Lin PC. Akt is a major angiogenic mediator downstream of the Ang1/Tie2 signaling pathway. Exp Cell Res 2004; 298: 167-177.
119. Zheng DQ, Woodard AS, Tallini G, Languino LR. Substrate specificity of alpha(v)beta(3) integrin-mediated cell migration and phosphatidylinositol 3-kinase/AKT pathway activation. J Biol Chem 2000; 275: 24565-24574.
120. Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol 2006; 27: 552-558.
121. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol 1995; 11: 73-91.
122. Kurz H. Physiology of angiogenesis. J Neurooncol 2000; 50: 17-35.
123. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-967.
124. Asahara T, Takahashi T, Masuda H, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 1999; 18: 3964-3972.
125. Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT. Angiogenesis in brain tumours. Nat Rev Neurosci 2007; 8: 610-622.
126. Zhang Z, Guth L. Experimental spinal cord injury: Wallerian degeneration in the dorsal column is followed by revascularization, glial proliferation, and nerve regeneration. Exp Neurol 1997; 147: 159-171.
127. Griffiths IR, McCulloch M, Crawford RA. Ultrastructural appearances of the spinal microvasculature between 12 hours and 5 days after impact injury. Acta Neuropathol 1978; 43: 205-211.
128. Baker KA, Hagg T. Developmental and injury-induced expression of alpha1beta1 and alpha6beta1 integrins in the rat spinal cord. Brain Res 2007; 1130: 54-66.
129. Mahoney ET, Benton RL, Maddie MA, Whittemore SR, Hagg T. ADAM8 is selectively up-regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice. J Comp Neurol 2009; 512: 243-255.
130. Patel CB, Cohen DM, Ahobila-Vajjula P, Sundberg LM, Chacko T, Narayana PA. Effect of VEGF treatment on the blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced magnetic resonance imaging. J Neurotrauma 2009; 26: 1005-1016.
131. van Neerven S, Joosten EA, Brook GA, et al. Repetitive intrathecal VEGF(165) treatment has limited therapeutic effects after spinal cord injury in the rat. J Neurotrauma 2010; 27: 1781-1791.
132. Benton RL, Whittemore SR. VEGF165 therapy exacerbates secondary damage following spinal cord injury. Neurochem Res 2003; 28: 1693-1703.
133. Nunes SS, Greer KA, Stiening CM, et al. Implanted microvessels progress through distinct neovascularization phenotypes. Microvasc Res 2010; 79: 10-20.
134. Lorquet S, Berndt S, Blacher S, et al. Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment. FASEB J 2010; 24: 3782-3795.
135. Hamzah J, Jugold M, Kiessling F, et al. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature 2008; 453: 410-414.
136. Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383: 707-710.
137. Andre C. CADASIL: pathogenesis, clinical and radiological findings and treatment. Arq Neuropsiquiatr 2010; 68: 287-299.
138. Gridley T. Notch signaling in vascular development and physiology. Development 2007; 134: 2709-2718.
139. Dvorak HF. VPF/VEGF and the angiogenic response. Semin Perinatol 2000; 24: 75-78.
140. Bareyre FM, Schwab ME. Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci 2003; 26: 555-563.
141. Widenfalk J, Lipson A, Jubran M, et al. Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience 2003; 120: 951-960.
142. Karsan A. The role of notch in modeling and maintaining the vasculature. Can J Physiol Pharmacol 2005; 83: 14-23.
143. Liu ZJ, Shirakawa T, Li Y, et al. Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis. Mol Cell Biol 2003; 23: 14-25.
144. Hellstrom M, Phng LK, Hofmann JJ, et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 2007; 445: 776-780.
145. Roca C, Adams RH. Regulation of vascular morphogenesis by Notch signaling. Genes Dev 2007; 21: 2511-2524.
146. Cecchi F, Rabe DC, Bottaro DP. Targeting the HGF/Met signalling pathway in cancer. Eur J Cancer 2010; 46: 1260-1270.
147. van Belle E, Witzenbichler B, Chen D, et al. Potentiated angiogenic effect of scatter factor/hepatocyte growth factor via induction of vascular endothelial growth factor: the case for paracrine amplification of angiogenesis. Circulation 1998; 97: 381-390.
148. Maemura M, Yoshimoto A, Tsukada Y, et al. Inhibitory effect of c-Met mutants on the formation of branching tubules by a porcine aortic endothelial cell line. Cancer Sci 2006; 97: 1343-1350.
149. Nagayama T, Nagayama M, Kohara S, et al. Post-ischemic delayed expression of hepatocyte growth factor and c-Met in mouse brain following focal cerebral ischemia. Brain Res 2004; 999: 155-166.
150. Ponce ML, Nomizu M, Kleinman HK. An angiogenic laminin site and its antagonist bind through the alpha(v)beta3 and alpha5beta1 integrins. FASEB J 2001; 15: 1389-1397.
151. Ponce ML, Nomizu M, Delgado MC, et al. Identification of endothelial cell binding sites on the laminin gamma 1 chain. Circ Res 1999; 84: 688-694.
152. Glaser J, Gonzalez R, Sadr E, Keirstead HS. Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury. J Neurosci Res 2006; 84: 724-734.
153. Majka M, Janowska-Wieczorek A, Ratajczak J, et al. Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 2001; 97: 3075-3085.
154. Schlaeger TM, Bartunkova S, Lawitts JA, et al. Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice. Proc Natl Acad Sci U S A 1997; 94: 3058-3063.
155. Motoike T, Loughna S, Perens E, et al. Universal GFP reporter for the study of vascular development. Genesis 2000; 28: 75-81.
156. Ohtsuki S, Kamiya N, Hori S, Terasaki T. Vascular endothelium-selective gene induction by Tie2 promoter/enhancer in the brain and retina of a transgenic rat. Pharm Res 2005; 22: 852-857.
157. De Palma M, Venneri MA, Galli R, et al. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 2005; 8: 211-226.
158. Arai F, Hirao A, Ohmura M, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004; 118: 149-161.
159. Srinivas S, Watanabe T, Lin CS, et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol 2001; 1: 4.
160. Alva JA, Zovein AC, Monvoisin A, et al. VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells. Dev Dyn 2006; 235: 759-767.
161. Monvoisin A, Alva JA, Hofmann JJ, Zovein AC, Lane TF, Iruela-Arispe ML. VE-cadherin-CreERT2 transgenic mouse: a model for inducible recombination in the endothelium. Dev Dyn 2006; 235: 3413-3422.
162. Forde A, Constien R, Grone HJ, Hammerling G, Arnold B. Temporal Cre-mediated recombination exclusively in endothelial cells using Tie2 regulatory elements. Genesis 2002; 33: 191-197.
163. Dray C, Rougon G, Debarbieux F. Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cord. Proc Natl Acad Sci USA 2009; 106: 9459-9464.
164. Cao Q, Xu XM, Devries WH, et al. Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. J Neurosci 2005; 25: 6947-6957.