Skip to main content

Advertisement

SpringerLink
Log in

Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Spinal cord injury causes immediate damage of nervous tissue accompanied by the loss of motor and sensory function. The limited self-repair ability of damaged nervous tissue underlies the need for reparative interventions to restore function after spinal cord injury. Blood vessels play a crucial role in spinal cord injury and repair. Injury-induced loss of local blood vessels and a compromised blood–brain barrier contribute to inflammation and ischemia and thus to the overall damage to the nervous tissue of the spinal cord. Lack of vasculature and leaking blood vessels impede endogenous tissue repair and limit prospective repair approaches. A reduction of blood vessel loss and the restoration of blood vessels so that they no longer leak might support recovery from spinal cord injury. The promotion of new blood vessel formation (i.e., angio- and vasculogenesis) might aid repair but also incorporates the danger of exacerbating tissue loss and thus functional impairment. The delicate interplay between cells and molecules that govern blood vessel repair and formation determines the extent of damage and the success of reparative interventions. This review deals with the cellular and molecular mechanisms underlying the role of blood vessels in spinal cord injury and repair.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8:464–478

    PubMed  CAS  Google Scholar 

  • Allen AR (1914) Remarks on the histopathological changes in the spinal cord due to impact. An experimental study. J Nerv Ment Dis 41:141–1147

    Google Scholar 

  • Alvarez JI, Dodelet-Devillers A, Kebir H, Ifergan I, Fabre PJ, Terouz S, Sabbagh M, Wosik K, Bourbonnière L, Bernard M, Horssen J van, Vries HE de, Charron F, Prat A (2011) The hedgehog pathway promotes blood–brain barrier integrity and CNS immune quiescence. Science 334:1727–1731

    PubMed  CAS  Google Scholar 

  • Anderson TE, Stokes BT (1992) Experimental models for spinal cord injury research: physical and physiological considerations. J Neurotrauma 9:135–142

    Google Scholar 

  • Anderson RG, Kamen BA, Rothberg KG, Lacey SW (1992) Potocytosis: sequestration and transport of small molecules by caveolae. Science 255:410–411

    PubMed  CAS  Google Scholar 

  • Armulik A, Genové G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21:193–215

    PubMed  CAS  Google Scholar 

  • Asahi M, Asahi K, Jung JC, Zoppo GJ del, Fini ME, Lo EH (2000) Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab 20:1681–1689

    PubMed  CAS  Google Scholar 

  • Banfi A, Degenfeld G von, Gianni-Barrera R, Reginato S, Merchant MJ, McDonald DM, Blau HM (2012) Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB. FASEB J (in press)

  • Batchelor PE, Porritt MJ, Nilsson SK, Bertoncello I, Donnan GA, Howells DW (2002) Periwound dopaminergic sprouting is dependent on numbers of wound macrophages. Eur J Neurosci 15:826–832

    PubMed  CAS  Google Scholar 

  • Bednar MM (2008) The role of sildenafil in the treatment of stroke. Curr Opin Investig Drugs 9:754–759

    PubMed  CAS  Google Scholar 

  • Benjamin LE, Hemo I, Keshet E (1998) A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125:1591–1598

    PubMed  CAS  Google Scholar 

  • Benton RL, Whittemore SR (2003) VEGF165 therapy exacerbates secondary damage following spinal cord injury. Neurochem Res 28:1693–1703

    PubMed  CAS  Google Scholar 

  • Benton RL, Maddie MA, Minnillo DR, Hagg T, Whittemore SR (2008) Griffonia simplicifolia isolectin B4 identifies a specific subpopulation of angiogenic blood vessels following contusive spinal cord injury in the adult mouse. J Comp Neurol 507:1031–1052

    PubMed  Google Scholar 

  • Bentzel CJ, Hainau B, Edelman A, Anagnostopoulos T, Benedetti EL (1976) Effect of plant cytokinins on microfilaments and tight junction permeability. Nature 264:666–668

    PubMed  CAS  Google Scholar 

  • Berg ME van den, Castellote JM, Mahillo-Fernandez I, Pedro-Cuesta J de (2010) Incidence of spinal cord injury worldwide: a systematic review. Neuroepidemiology 34:184–192

    PubMed  Google Scholar 

  • Bertram JP, Williams CA, Robinson R, Segal SS, Flynn NT, Lavik EB (2009) Intravenous hemostat: nanotechnology to halt bleeding. Sci Transl Med 1:11ra22

    PubMed  Google Scholar 

  • Blight AR (1991) Morphometric analysis of blood vessels in chronic experimental spinal cord injury: hypervascularity and recovery of function. J Neurol Sci 106:158–174

    PubMed  CAS  Google Scholar 

  • Bo X, Wu D, Yeh J, Zhang Y (2011) Gene therapy approaches for neuroprotection and axonal regeneration after spinal cord and spinal root injury. Curr Gene Ther 11:101–115

    PubMed  CAS  Google Scholar 

  • Boyd NL, Park H, Yi H, Boo YC, Sorescu GP, Sykes M, Jo H (2003) Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells. Am J Physiol Heart Circ Physiol 285:H1113–H1122

    PubMed  CAS  Google Scholar 

  • Bramlett HM, Dietrich WD (2007) Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res 161:125–141

    PubMed  Google Scholar 

  • Brightman MW, Zis K, Anders J (1983) Morphology of cerebral endothelium and astrocytes as determinants of the neuronal microenvironment. Acta Neuropathol Suppl (Berl) 8:21–33

    CAS  Google Scholar 

  • Brines ML, Ghezzi P, Keenan S, Agnello D, De Lanerolle NC, Cerami C, Itri LM, Cerami A (2000) Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 97:10526–10531

    PubMed  CAS  Google Scholar 

  • Bullock R, Fujisawa H (1992) The role of glutamate antagonists for the treatment of CNS injury. J Neurotrauma 9 (Suppl 2):S443–S462

    PubMed  Google Scholar 

  • Candelario-Jalil E, Yang Y, Rosenberg GA (2008) Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 158:983–994

    PubMed  Google Scholar 

  • Cao Q, Zhang YP, Iannotti C, DeVries WH, Xu XM, Shields CB, Whittemore SR (2005) Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat. Exp Neurol 191:S3–S16

    PubMed  Google Scholar 

  • Carelli S, Marfia G, Di Giulio AM, Ghilardi G, Gorio A (2011) Erythropoietin: recent developments in the treatment of spinal cord injury. Neurol Res Int 2011:453179

    PubMed  Google Scholar 

  • Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936

    PubMed  CAS  Google Scholar 

  • Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    PubMed  CAS  Google Scholar 

  • Casella GT, Marcillo A, Bunge MB, Wood PM (2002) New vascular tissue rapidly replaces neural parenchyma and vessels destroyed by a contusion injury to the rat spinal cord. Exp Neurol 173:63–76

    PubMed  Google Scholar 

  • Casella GT, Bunge MB, Wood PM (2006) Endothelial cell loss is not a major cause of neuronal and glial cell death following contusion injury of the spinal cord. Exp Neurol 202:8–20

    PubMed  Google Scholar 

  • Cherian L, Goodman JC, Robertson C (2007) Neuroprotection with erythropoietin administration following controlled cortical impact injury in rats. J Pharmacol Exp Ther 322:789–794

    PubMed  CAS  Google Scholar 

  • Chiu WT, Lin HC, Lam C, Chu SF, Chiang YH, Tsai SH (2010) Review paper: epidemiology of traumatic spinal cord injury: comparisons between developed and developing countries. Asia Pac J Publ Health 22:9–18

    Google Scholar 

  • Chopp M, Li Y (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurol 1:92–100

    PubMed  Google Scholar 

  • Côté MP, Amin AA, Tom VJ, Houle JD (2011) Peripheral nerve grafts support regeneration after spinal cord injury. Neurotherapeutics 8:294–303

    PubMed  Google Scholar 

  • Cripps RA, Lee BB, Wing P, Weerts E, Mackay J, Brown D (2011) A global map for traumatic spinal cord injury epidemiology: towards a living data repository for injury prevention. Spinal Cord 49:493–501

    PubMed  CAS  Google Scholar 

  • Dallasta LM, Pisarov LA, Esplen JE, Werley JV, Moses AV, Nelson JA, Achim CL (1999) Blood–brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. Am J Pathol 155:1915–1927

    PubMed  CAS  Google Scholar 

  • Darland DC, D’Amore PA (2001) TGFβ is required for the formation of capillary-like structures in three-dimensional cocultures of 10 T1/2 and endothelial cells. Angiogenesis 4:11–20

    PubMed  CAS  Google Scholar 

  • Davis GE, Stratman AN, Sacharidou A, Koh W (2011) Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting. Int Rev Cell Mol Biol 288:101–165

    PubMed  CAS  Google Scholar 

  • De Winter F, Oudega M, Lankhorst AJ, Hamers FP, Blits B, Ruitenberg MJ, Pasterkamp RJ, Gispen WH, Verhaagen J (2002) Injury-induced class 3 semaphorin expression in the rat spinal cord. Exp Neurol 175:61–75

    PubMed  Google Scholar 

  • Dobrogowska DH, Lossinsky AS, Tarnawski M, Vorbrodt AW (1998) Increased blood–brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor. J Neurocytol 27:163–173

    PubMed  CAS  Google Scholar 

  • Dray C, Rougon G, Debarbieux F (2009) Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cord. Proc Natl Acad Sci USA 106:9459–9464

    PubMed  CAS  Google Scholar 

  • Dumont DJ, Gradwohl GJ, Fong GH, Auerbach R, Breitman ML (1993) The endothelial-specific receptor tyrosine kinase, tek, is a member of a new subfamily of receptors. Oncogene 8:1293–1301

    PubMed  CAS  Google Scholar 

  • Ek CJ, Habgood MD, Callaway JK, Dennis R, Dziegielewska KM, Johansson PA, Potter A, Wheaton B, Saunders NR (2010) Spatio-temporal progression of grey and white matter damage following contusion injury in rat spinal cord. PLoS One 5:e12021

    PubMed  Google Scholar 

  • Fassbender JM, Whittemore SR, Hagg T (2011) Targeting microvasculature for neuroprotection after SCI. Neurotherapeutics 8:240–251

    PubMed  Google Scholar 

  • Fehlings MG, Tator CH, Linden RD (1989) The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury. J Neurosurg 71:403–416

    PubMed  CAS  Google Scholar 

  • Ford MC, Bertram JP, Hynes SR, Michaud M, Li Q, Young M, Segal SS, Madri JA, Lavik EB (2006) A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo. Proc Natl Acad Sci USA 103:2512–2517

    PubMed  CAS  Google Scholar 

  • Frank PG, Woodman SE, Park DS, Lisanti MP (2003) Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol 23:1161–1168

    PubMed  CAS  Google Scholar 

  • Frank PG, Pavlides S, Lisanti MP (2009) Caveolae and transcytosis in endothelial cells: role in atherosclerosis. Cell Tissue Res 335:41–47

    PubMed  CAS  Google Scholar 

  • Furuse M, Tsukita S (2006) Claudins in occluding junctions of humans and flies. Trends Cell Biol 16:181–188

    PubMed  CAS  Google Scholar 

  • Gamble JR, Drew J, Trezise L, Underwood A, Parsons M, Kasminkas L, Rudge J, Yancopoulos G, Vadas MA (2000) Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions. Circ Res 87:603–607

    PubMed  CAS  Google Scholar 

  • Gao F, Sugita M, Nukui H (2005) Phosphodiesterase 5 inhibitor, zaprinast, selectively increases cerebral blood flow in the ischemic penumbra in the rat brain. Neurol Res 27:638–643

    PubMed  CAS  Google Scholar 

  • Goritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisen J (2011) A pericyte origin of spinal cord scar tissue. Science 333:238–242

    PubMed  Google Scholar 

  • Grasso G, Sfacteria A, Cerami A, Brines M (2004) Erythropoietin as a tissue-protective cytokine in brain injury: what do we know and where do we go?Neuroscientist 10:93–98

    PubMed  CAS  Google Scholar 

  • Griffiths IR, Burns N, Crawford AR (1978) Early vascular changes in the spinal grey matter following impact injury. Acta Neuropathol 41:33–39

    PubMed  CAS  Google Scholar 

  • Gruner JA (1992) A monitored contusion model of spinal cord injury in the rat. J Neurotrauma 9:123–126

    PubMed  CAS  Google Scholar 

  • Guízar-Sahagún G, Velasco-Hernández L, Martínez-Cruz A, Castañeda-Hernández G, Bravo G, Rojas G, Hong E (2004) Systemic microcirculation after complete high and low thoracic spinal cord section in rats. J Neurotrauma 21:1614–1623

    PubMed  Google Scholar 

  • Guo X, Liu L, Zhang M, Bergeron A, Cui Z, Dong JF, Zhang J (2009) Correlation of CD34+ cells with tissue angiogenesis after traumatic brain injury in a rat model. J Neurotrauma 26:1337–1344

    PubMed  Google Scholar 

  • Habgood MD, Bye N, Dziegielewska KM, Ek CJ, Lane MA, Potter A, Morganti-Kossmann C, Saunders NR (2007) Changes in blood–brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci 25:231–238

    PubMed  CAS  Google Scholar 

  • Hagg T (2006) Collateral sprouting as a target for improved function after spinal cord injury. J Neurotrauma 23:281–294

    PubMed  Google Scholar 

  • Hagg T, Oudega M (2006) Degenerative and spontaneous regenerative processes after spinal cord injury. J Neurotrauma 23:264–280

    PubMed  Google Scholar 

  • Hall ED (1995) Inhibition of lipid peroxidation in central nervous system trauma and ischemia. J Neurol Sci 134 (suppl):79–83

    PubMed  Google Scholar 

  • Hall ED, Braughler JM (1986) Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review. Cent Nerv Syst Trauma 3:281–294

    PubMed  CAS  Google Scholar 

  • Hall ED, Springer JE (2004) Neuroprotection and acute spinal cord injury: a reappraisal.NeuroRx 1:80-100

    PubMed  Google Scholar 

  • Hall ED, McCall JM, Means ED (1994) Therapeutic potential of the lazaroids (21-aminosteroids) in acute central nervous system trauma, ischemia and subarachnoid hemorrhage. Adv Pharmacol 28:221–268

    PubMed  CAS  Google Scholar 

  • Han S, Arnold SA, Sithu SD, Mahoney ET, Geralds JT, Tran P, Benton RL, Maddie MA, D’Souza SE, Whittemore SR, Hagg T (2010) Rescuing vasculature with intravenous angiopoietin-1 and alpha v beta 3 integrin peptide is protective after spinal cord injury. Brain 133:1026–1042

    PubMed  Google Scholar 

  • Hardebo JE, Kahrstrom J (1985) Endothelial negative surface charge areas and blood–brain barrier function. Acta Physiol Scand 125:495–499

    PubMed  CAS  Google Scholar 

  • Hassler O (1966) Blood supply to human spinal cord. A microangiographic study. Arch Neurol 15:302–307

    PubMed  CAS  Google Scholar 

  • Hawighorst T, Skobe M, Streit M, Hong YK, Velasco P, Brown LF, Riccardi L, Lange-Asschenfeldt B, Detmar M (2002) Activation of the tie2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth. Am J Pathol 160:1381–1392

    PubMed  CAS  Google Scholar 

  • Hawkins BT, Lundeen TF, Norwood KM, Brooks HL, Egleton RD (2007) Increased blood–brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases. Diabetologia 50:202–211

    PubMed  CAS  Google Scholar 

  • Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-β in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055

    PubMed  CAS  Google Scholar 

  • Hill CE, Hurtado A, Blits B, Bahr BA, Wood PM, Bartlett Bunge M, Oudega M (2007) Early necrosis and apoptosis of Schwann cells transplanted into the injured rat spinal cord. Eur J Neurosci 26:1433–1445

    PubMed  Google Scholar 

  • Hong Z, Hong H, Chen H, Wang Z, Hong D (2012) Protective effects of erythropoietin in experimental spinal cord injury by reducing the C/EBP-homologous protein expression. Neurol Res 34:85–90

    PubMed  Google Scholar 

  • Hsu CY, Hogan EL, Gadsden RH Sr, Spicer KM, Shi MP, Cox RD (1985) Vascular permeability in experimental spinal cord injury. J Neurol Sci 70:275–282

    PubMed  CAS  Google Scholar 

  • Huang FJ, You WK, Bonaldo P, Seyfried TN, Pasquale EB, Stallcup WB (2010) Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse. Dev Biol 344:1035–1046

    PubMed  CAS  Google Scholar 

  • Hurtado A, Moon LD, Maquet V, Blits B, Jérôme R, Oudega M (2006) Poly (D, L-lactic acid) macroporous guidance scaffolds seeded with Schwann cells genetically modified to secrete a bi-functional neurotrophin implanted in the completely transected adult rat thoracic spinal cord. Biomaterials 27:430–442

    PubMed  CAS  Google Scholar 

  • Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25

    PubMed  CAS  Google Scholar 

  • Imperato-Kalmar EL, McKinney RA, Schnell L, Rubin BP, Schwab ME (1997) Local changes in vascular architecture following partial spinal cord lesion in the rat. Exp Neurol 145:322–328

    PubMed  CAS  Google Scholar 

  • Jain RK, Tomaso E di, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT (2007) Angiogenesis in brain tumours. Nat Rev Neurosci 8:610–622

    PubMed  CAS  Google Scholar 

  • Joshi M, Fehlings MG (2002) Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse. Part 1. Clip design, behavioral outcomes, and histopathology. J Neurotrauma 19:175–190

    PubMed  Google Scholar 

  • Kakulas BA (1999) A review of the neuropathology of human spinal cord injury with emphasis on special features. J Spinal Cord Med 22:119–124

    PubMed  CAS  Google Scholar 

  • Kaneko S, Iwanami A, Nakamura M, Kishino A, Kikuchi K, Shibata S, Okano HJ, Ikegami T, Moriya A, Konishi O, Nakayama C, Kumagai K, Kimura T, Sato Y, Goshima Y, Taniguchi M, Ito M, He Z, Toyama Y, Okano H (2006) A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med 12:1380–1389

    PubMed  CAS  Google Scholar 

  • Kim I, Kim HG, So JN, Kim JH, Kwak HJ, Koh GY (2000) Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Circ Res 86:24–29

    PubMed  CAS  Google Scholar 

  • Kim KT, Choi HH, Steinmetz MO, Maco B, Kammerer RA, Ahn SY et al (2005) Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2. J Biol Chem 280:20126–20131

    PubMed  CAS  Google Scholar 

  • Kim JH, Jung Y, Kim SH, Sun K, Choi J, Kim HC, Park Y, Kim SH (2011) The enhancement of mature vessel formation and cardiac function in infracted hearts using dual growth factor delivery with self-assembling peptides. Biomaterials 32:6080–6088

    PubMed  CAS  Google Scholar 

  • Krassioukov AV, Furlan JC, Fehlings MG (2003) Autonomic dysreflexia in acute spinal cord injury: an under-recognized clinical entity. J Neurotrauma 20:707–716

    PubMed  Google Scholar 

  • Kurz H (2000) Physiology of angiogenesis. J Neurooncol 50:17–35

    PubMed  CAS  Google Scholar 

  • Kwon BK, Oxland TR, Tetzlaff W (2002) Animal models used in spinal cord regeneration research. Spine 27:1504–1510

    PubMed  Google Scholar 

  • Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4:451–464

    PubMed  Google Scholar 

  • Lee SW, Kim WJ, Jun HO, Choi YK, Kim KW (2009) Angiopoietin-1 reduces vascular endothelial growth factor-induced brain endothelial permeability via upregulation of ZO-2. Int J Mol Med 23:279–284

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Li B, Mahmood A, Lu D, Wu H, Xiong Y, Qu C, Chopp M (2009) Simvastatin attenuates microglial cells and astrocyte activation and decreases interleukin-1beta level after traumatic brain injury. Neurosurgery 65:179–185

    PubMed  Google Scholar 

  • Li L, Jiang Q, Zhang L, Ding G, Gang Zhang Z, Li Q, Ewing JR, Lu M, Panda S, Ledbetter KA, Whitton PA et al (2007) Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke. Brain Res 1132:185–192

    PubMed  CAS  Google Scholar 

  • Li Q, Ford MC, Lavik EB, Madri JA (2006) Modeling the neurovascular niche: VEGF- and BDNF-mediated cross-talk between neural stem cells and endothelial cells: an in vitro study. J Neurosci Res 84:1656–1668

    PubMed  CAS  Google Scholar 

  • Li X, Hahn CN, Parsons M, Drew J, Vadas MA, Gamble JR (2004) Role of protein kinase Czeta in thrombin-induced endothelial permeability changes: inhibition by angiopoietin-1. Blood 104:1716–1724

    PubMed  CAS  Google Scholar 

  • Liebner S, Czupalla CJ, Wolburg H (2011) Current concepts of blood–brain barrier development. Int J Dev Biol 55:467–476

    PubMed  CAS  Google Scholar 

  • Lok J, Gupta P, Guo S, Kim WJ, Whalen MJ, Van Leyen K, Lo EH (2007) Cell-cell signaling in the neurovascular unit. Neurochem Res 32:2032–2045

    PubMed  CAS  Google Scholar 

  • Lossinsky AS, Shivers RR (2004) Structural pathways for macromolecular and cellular transport across the blood–brain barrier during inflammatory conditions. Histol Histopathol 19:535–564

    PubMed  CAS  Google Scholar 

  • Lovasik D (1999) The older patient with a spinal cord injury. Crit Care Nurs Q 22:20–30

    PubMed  CAS  Google Scholar 

  • Loy DN, Crawford CH, Darnall JB, Burke DA, Onifer SM, Whittemore SR (2002) Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat. J Comp Neurol 445:308–324

    PubMed  Google Scholar 

  • Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, Chopp M (2004a) Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. J Neurotrauma 21:21–32

    PubMed  Google Scholar 

  • Lu D, Mahmood A, Goussev A, Schallert T, Qu C, Zhang ZG, Li Y, Lu M, Chopp M (2004b) Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury. J Neurosurg 101:813–821

    PubMed  CAS  Google Scholar 

  • Lu D, Mahmood A, Qu C, Goussev A, Schallert T, Chopp M (2005) Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury. J Neurotrauma 22:1011–1017

    PubMed  Google Scholar 

  • Madeddu P (2005) Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp Physiol 90:315–326

    PubMed  CAS  Google Scholar 

  • Mahmood A, Lu D, Chopp M (2004) Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 21:33–39

    PubMed  Google Scholar 

  • Mahmood A, Lu D, Qu C, Goussev A, Zhang ZG, Lu C, Chopp M (2007) Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin. J Neurosurg 107:392–397

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Makinde T, Agrawal DK (2008) Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease. J Cell Mol Med 12:810–828

    PubMed  CAS  Google Scholar 

  • Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K (1999) Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J Biol Chem 274:21217–21222

    PubMed  CAS  Google Scholar 

  • Mammis A, Mcintosh TK, Maniker AH (2009) Erythropoietin as a neuroprotective agent in traumatic brain injury Review. Surg Neurol 71:527–531

    PubMed  Google Scholar 

  • Matsumoto M, Iida Y, Wakamatsu H, Ohtake K, Nakakimura K, Xiong L, Sakabe T (1999) The effects of N(G)-nitro-L-arginine-methyl ester on neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits. Anesth Analg 89:696–702

    PubMed  CAS  Google Scholar 

  • Mautes AE, Weinzierl MR, Donovan F, Noble LJ (2000) Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther 80:673–687

    PubMed  CAS  Google Scholar 

  • McCreedy DA, Sakiyama-Elbert SE (2012) Combination therapies in the CNS: engineering the environment. Neurosci Lett (in press)

  • Means ED, Anderson DK, Nicolosi G, Gaudsmith J (1978) Microvascular perfusion experimental spinal cord injury. Surg Neurol 9:353–360

    PubMed  CAS  Google Scholar 

  • Minshall RD, Sessa WC, Stan RV, Anderson RG, Malik AB (2003) Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol 285:L1179–L1183

    PubMed  CAS  Google Scholar 

  • Mondrinos MJ, Koutzaki SH, Poblete HM, Crisanti MC, Lelkes PI, Finck CM (2008) In vivo pulmonary tissue engineering: contribution of donor-derived endothelial cells to construct vascularization. Tissue Eng Part A 14:361–368

    PubMed  CAS  Google Scholar 

  • Morita K, Furuse M, Fujimoto K, Tsukita S (1999) Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci USA 96:511–516

    PubMed  CAS  Google Scholar 

  • Nag S (1995) Role of the endothelial cytoskeleton in blood–brain-barrier permeability to protein. Acta Neuropathol (Berl) 90:454–460

    CAS  Google Scholar 

  • Nag S (2007) Structure and pathology of the blood–brain barrier. In: Lathja A (ed) Handbook of neurochemistry and molecular neurobiology. Springer, New York, pp 58–78

    Google Scholar 

  • Nag S, Eskandarian MR, Davis J, Eubanks JH (2002) Differential expression of vascular endothelial growth factor-A (VEGF-A) and VEGF-B after brain injury. J Neuropathol Exp Neurol 61:778–788

    PubMed  CAS  Google Scholar 

  • Nag S, Papneja T, Venugopalan R, Stewart DJ (2005) Increased angiopoietin2 expression is associated with endothelial apoptosis and blood–brain barrier breakdown. Lab Invest 85:1189–1198

    PubMed  CAS  Google Scholar 

  • Nag S, Manias JL, Stewart DJ (2009) Expression of endothelial phosphorylated caveolin-1 is increased in brain injury. Neuropathol Appl Neurobiol 35:417–426

    PubMed  CAS  Google Scholar 

  • Nag S, Kapadia A, Stewart DJ (2011) Review: molecular pathogenesis of blood–brain barrier breakdown in acute brain injury. Neuropathol Appl Neurobiol 37:3–23

    PubMed  CAS  Google Scholar 

  • Nagy Z, Peters H, Huttner I (1983) Charge-related alterations of the cerebral endothelium. Lab Invest 49:662–671

    PubMed  CAS  Google Scholar 

  • Nakano N, Nakai Y, Seo TB, Yamada Y, Ohno T, Yamanaka A, Nagai Y, Fukushima M, Suzuki Y, Nakatani T, Ide C (2010) Characterization of conditioned medium of cultured bone marrow stromal cells. Neurosci Lett 483:57–61

    PubMed  CAS  Google Scholar 

  • Nandoe Tewarie RD, Hurtado A, Ritfeld GJ, Rahiem ST, Wendell DF, Barroso MM, Grotenhuis JA, Oudega M (2009) Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord. J Neurotrauma 26:2313–2322

    PubMed  Google Scholar 

  • Nandoe Tewarie RD, Bossers K, Ritfeld GJ, Blits B, Grotenhuis JA, Verhaagen J, Oudega M (2011) Early passage bone marrow stromal cells express genes involved in nervous system development supporting their relevance for neural repair. Restor Neurol Neurosci 29:187–201

    PubMed  CAS  Google Scholar 

  • Nico B, Frigeri A, Nicchia GP, Corsi P, Ribatti D, Quondamatteo F, Herken R, Girolamo F, Marzullo A, Svelto M, Roncali L (2003) Severe alterations of endothelial and glial cells in the blood–brain barrier of dystrophic mdx mice. Glia 42:235–251

    PubMed  Google Scholar 

  • Noble LJ, Wrathall JR (1989) Distribution and time course of protein extravasion in the rat spinal cord after contusive injury. Brain Res 482:57–66

    PubMed  CAS  Google Scholar 

  • Noble LJ, Donovan F, Igarashi T, Goussev S, Werb Z (2002) Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. J Neurosci 22:7526–7535

    PubMed  CAS  Google Scholar 

  • Nusrat A, Parkos CA, Verkade P, Foley CS, Liang TW, Innis-Whitehouse W, Eastburn KK, Madara JL (2000) Tight junctions are membrane microdomains. J Cell Sci 113:1771–1781

    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

    PubMed  CAS  Google Scholar 

  • Olofsson B, Pajusola K, Euler G von, Chilov D, Alitalo K, Eriksson U (1996) Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform. J Biol Chem 271:19310–19317

    PubMed  CAS  Google Scholar 

  • Onifer SM, Smith GM, Fouad K (2011) Plasticity after spinal cord injury: relevance to recovery and approaches to facilitate it. Neurotherapeutics 8:283–293

    PubMed  Google Scholar 

  • Onimaru M, Yonemitsu Y, Fujii T, Tanii M, Nakano T, Nakagawa K, Kohno R, Hasegawa M, Nishikawa S, Sueishi K (2009) VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B. Am J Physiol Heart Circ Physiol 297:H1685–H1696

    PubMed  CAS  Google Scholar 

  • Oudega M (2010) Spinal cord injury and repair: role of blood vessel loss and endogenous angiogenesis. Adv Wound Care 1:335–340

    Google Scholar 

  • Papapetropoulos A, Fulton D, Mahboubi K, Kalb RG, OConnor DS, Li FZ, Altieri DC, Sessa WC (2000) Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway. J Biol Chem 275:9102–9105

    PubMed  CAS  Google Scholar 

  • Parat MO (2009) The biology of caveolae: achievements and perspectives. Int Rev Cell Mol Biol 273:117–162

    PubMed  CAS  Google Scholar 

  • Paul R, Zhang ZG, Eliceiri BP, Jiang Q, Boccia AD, Zhang RL, Chopp M, Cheresh DA (2001) Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat Med 7:222–227

    PubMed  CAS  Google Scholar 

  • Pinzon A, Marcillo A, Pabon D, Bramlett HM, Bunge MB, Dietrich WD (2008) A re-assessment of erythropoietin as a neuroprotective agent following rat spinal cord compression or contusion injury. Exp Neurol 213:129–136

    PubMed  CAS  Google Scholar 

  • Popovich PG (2000) Immunological regulation of neuronal degeneration and regeneration in the injured spinal cord. Prog Brain Res 28:43–58

    Google Scholar 

  • Puri MC, Rossant J, Alitalo K, Bernstein A, Partanen J (1995) The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. EMBO J 14:5884–5891

    PubMed  CAS  Google Scholar 

  • Raineteau O, Schwab ME (2001) Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci 2:263–273

    PubMed  CAS  Google Scholar 

  • Rauch MF, Hynes SR, Bertram J, Redmond A, Robinson R, Williams C, Xu H, Madri JA, Lavik EB (2009) Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier. Eur J Neurosci 29:132–145

    PubMed  Google Scholar 

  • Reginato S, Gianni-Barrera R, Banfi A (2011) Taming of the wild vessel: promoting vessel stabilization for safe therapeutic angiogenesis. Biochem Soc Trans 39:1654–1658

    PubMed  CAS  Google Scholar 

  • Richardson RM, Sun D, Bullock MR (2007) Neurogenesis after traumatic brain injury. Neurosurg Clin N Am 18:169–181

    PubMed  Google Scholar 

  • Richter T, Floetenmeyer M, Ferguson C, Galea J, Goh J, Lindsay MR, Morgan GP, Marsh BJ, Parton RG (2008) High-resolution 3D quantitative analysis of caveolar ultrastructure and caveola-cytoskeleton interactions. Traffic 9:893–909

    PubMed  CAS  Google Scholar 

  • Ritfeld GJ, Nandoe Tewarie RD, Rahiem ST, Hurtado A, Roos RA, Grotenhuis A, Oudega M (2010) Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord. NeuroReport 21:221–226

    PubMed  CAS  Google Scholar 

  • Ritfeld GJ, Nandoe Tewarie R, Vajn K, Rahiem ST, Hurtado A, Wendell DF, Roos RA, Oudega M (2012) Bone marrow stromal cell-mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats. Cell Transplant (in press)

  • Rosenberg GA, Yang Y (2007) Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia. Neurosurg Focus 22:E4

    PubMed  Google Scholar 

  • Roy H, Bhardwaj S, Yla-Herttuala S (2006) Biology of vascular endothelial growth factors. FEBS Lett 580:2879–2887

    PubMed  CAS  Google Scholar 

  • Sacharidou A, Stratman AN, Davis GE (2012) Molecular mechanisms controlling vascular lumen formation in three-dimensional extracellular matrices. Cells Tissues Organs 195:122–143

    PubMed  CAS  Google Scholar 

  • Sadrzadeh SM, Eaton JW (1988) Hemoglobin-mediated oxidant damage to the central nervous system requires endogenous ascorbate. J Clin Invest 82:1510–1515

    PubMed  CAS  Google Scholar 

  • Sadrzadeh SM, Anderson DK, Panter SS, Hallaway PE, Eaton JW (1987) Hemoglobin potentiates central nervous system damage. J Clin Invest 79:662–664

    PubMed  CAS  Google Scholar 

  • Scheff SW, Rabchevsky AG, Fugaccia I, Main JA (2003) Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma 20:179–193

    PubMed  Google Scholar 

  • Segura I, De Smet F, Hohensinner PJ, Ruiz de Almodovar C, Carmeliet P (2009) The neurovascular link in health and disease: an update. Trends Mol Med 15:439–451

    PubMed  CAS  Google Scholar 

  • Shen F, Walker EJ, Jiang L, Degos V, Li J, Sun B, Heriyanto F, Young WL, Su H (2011) Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood–brain barrier and reduces atrophy volume. J Cereb Blood Flow Metab 31:2343–2351

    PubMed  CAS  Google Scholar 

  • Smith GM, Falone AE, Frank E (2012) Sensory axon regeneration: rebuilding functional connections in the spinal cord. Trends Neurosci 35:156–163

    PubMed  CAS  Google Scholar 

  • Smith SL, Scherch HM, Hall ED (1996) Protective effects of tirilazad mesylate and metabolite U-89678 against blood–brain barrier damage after subarachnoid hemorrhage and lipid peroxidative neuronal injury. J Neurosurg 84:229–233

    PubMed  CAS  Google Scholar 

  • Song L, Ge S, Pachter JS (2007) Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells. Blood 109:1515–1523

    PubMed  CAS  Google Scholar 

  • Stan RV (2007) Endothelial stomatal and fenestral diaphragms in normal vessels and angiogenesis. J Cell Mol Med 11:621–643

    PubMed  CAS  Google Scholar 

  • Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516

    PubMed  CAS  Google Scholar 

  • Tanaka S, Takehashi M, Iida S, Kitajima T, Kamanaka Y, Stedeford T, Banasik M, Ueda K (2005) Mitochondrial impairment induced by poly(ADP-ribose) polymerase-1 activation in cortical neurons after oxygen and glucose deprivation. J Neurochem 95:179–190

    PubMed  CAS  Google Scholar 

  • Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75:15–26

    PubMed  CAS  Google Scholar 

  • Tell D von, Armulik A, Betsholtz C (2006) Pericytes and vascular stability. Exp Cell Res 312:623–629

    Google Scholar 

  • Tetzlaff W, Alexander SW, Miller FD, Bisby MA (1991) Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43. J Neurosci 11:2528–2544

    PubMed  CAS  Google Scholar 

  • Thau-Zuchman O, Shohami E, Alexandrovich AG, Leker RR (2012) Combination of vascular endothelial and fibroblast growth factor 2 for induction of neurogenesis and angiogenesis after traumatic brain injury. J Mol Neurosci 47:166–172

    PubMed  CAS  Google Scholar 

  • Thomas CM, Smart EJ (2008) Caveolae structure and function. J Cell Mol Med 12:796–809

    PubMed  CAS  Google Scholar 

  • Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM (1999) Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 286:2511–2514

    PubMed  CAS  Google Scholar 

  • Turnbull IM, Brieg A, Hassler O (1966) Blood supply of cervical spinal cord in man. A microangiographic cadaver study. J Neurosurg 24:951–965

    PubMed  CAS  Google Scholar 

  • Wang L, Chopp M, Gregg SR, Zhang RL, Teng H, Jiang A, Feng Y, Zhang ZG (2008) Neural progenitor cells treated with EPO induce angiogenesis through the production of VEGF. J Cereb Blood Flow Metab 28:1361–1368

    PubMed  CAS  Google Scholar 

  • Wang W, Dentler WL, Borchardt RT (2001) VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly. Am J Physiol Heart Circ Physiol 280:H434–H440

    PubMed  CAS  Google Scholar 

  • Whetstone WD, Hsu JY, Eisenberg M, Werb Z, Noble-Haeusslein L (2003) Blood-spinal cord barrier after spinal cord injury: relation to revascularization and wound healing. J Neurosci Res 74:227–239

    PubMed  CAS  Google Scholar 

  • Wible EF, Laskowitz DT (2010) Statins in traumatic brain injury. Neurotherapeutics 7:62–73

    PubMed  CAS  Google Scholar 

  • Widenfalk J, Lipson A, Jubran M, Hofstetter C, Ebendal T, Cao Y, Olson I (2003) Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience 120:951–960

    PubMed  CAS  Google Scholar 

  • Wolburg H, Lippoldt A (2002) Tight junctions of the blood–brain barrier: development, composition and regulation. Vascul Pharmacol 38:323–337

    PubMed  CAS  Google Scholar 

  • Wolman L (1965)The disturbance of circulation in traumatic paraplegia in acute and late stages: a pathological study. Paraplegia 2:213–226

    PubMed  CAS  Google Scholar 

  • Wong AL, Haroon ZA, Werner S, Dewhirst MW, Greenberg CS, Peters KG (1997) Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues. Circ Res 81:567–574

    PubMed  CAS  Google Scholar 

  • Wu H, Lu D, Jiang H, Xiong Y, Qu C, Li B, Mahmood A, Zhou D, Chopp M (2008) Increase in phosphorylation of Akt and its downstream signaling targets and suppression of apoptosis by simvastatin after traumatic brain injury. J Neurosurg 109:691–698

    PubMed  CAS  Google Scholar 

  • Xiong Y, Lu D, Qu C, Goussev A, Schallert T, Mahmood A, Chopp M (2008) Effects of erythropoietin on reducing brain damage and improving functional outcome after traumatic brain injury in mice. J Neurosurg 109:510–521

    PubMed  Google Scholar 

  • Xiong Y, Mahmood A, Chopp M (2010a) Neurorestorative treatments for traumatic brain injury. Discov Med 10:434–442

    PubMed  Google Scholar 

  • Xiong Y, Mahmood A, Meng Y, Zhang Y, Qu C, Schallert T, Chopp M (2010b) Delayed administration of erythropoietin reducing hippocampal cell loss, enhancing angiogenesis and neurogenesis, and improving functional outcome following traumatic brain injury in rats: comparison of treatment with single and triple dose. J Neurosurg 113:598–608

    PubMed  CAS  Google Scholar 

  • Yamauchi T, Lin Y, Sharp FR, Noble-Haeusslein LJ (2004) Hemin induces heme oxygenase-1 in spinal cord vasculature and attenuates barrier disruption and neutrophil infiltration in the injured murine spinal cord. J Neurotrauma 21:1017–1030

    PubMed  Google Scholar 

  • Yan Z, Okutsu M, Akhtar YN, Lira VA (2011) Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle. J Appl Physiol 110:264–274

    PubMed  CAS  Google Scholar 

  • Young W (2002) Spinal cord contusion models. Prog Brain Res 137:231–255

    PubMed  Google Scholar 

  • Zacchigna S, Pattarini L, Zentilin L, Moimas S, Carrer A, Sinigaglia M, Arsic N, Tafuro S, Sinagra G, Giacca M (2008a) Bone marrow cells recruited through the neuropilin-1 receptor promote arterial formation at the sites of adult neoangiogenesis in mice. J Clin Invest 118:2062–2075

    PubMed  CAS  Google Scholar 

  • Zacchigna S, Lambrechts D, Carmeliet P (2008b) Neurovascular signalling defects in neurodegeneration. Nat Rev Neurosci 9:169–181

    PubMed  CAS  Google Scholar 

  • Zachary I (2005) Neuroprotective role of vascular endothelial growth factor: signalling mechanisms, biological function, and therapeutic potential. Neurosignals 14:207–221

    PubMed  CAS  Google Scholar 

  • Zagzag D, Amirnovin R, Greco MA, Yee H, Holash J, Wiegand SJ, Zabski S, Yancopoulos GD, Grumet M (2000) Vascular apoptosis and involution in gliomas precede neovascularization: a novel concept for glioma growth and angiogenesis. Lab Invest 80:837–849

    PubMed  CAS  Google Scholar 

  • Zhang L, Zhang Z, Zhang RL, Cui Y, LaPointe MC, Silver B, Chopp M (2006) Tadalafil, a long-acting type 5 phosphodiesterase isoenzyme inhibitor, improves neurological functional recovery in a rat model of embolic stroke. Brain Res 1118:192–198

    PubMed  CAS  Google Scholar 

  • Zhang L, Hu Y, Sun CY, Li J, Guo T, Huang J, Chu ZB (2010) Lentiviral shRNA silencing of BDNF inhibits in vivo multiple myeloma growth and angiogenesis via down-regulated stroma-derived VEGF expression in the bone marrow milieu. Cancer Sci 101:1117–1124

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ziegelhoeffer T, Fernandez B, Kostin S, Heil M, Voswinckel R, Helisch A, Schaper W (2004) Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res 94:230–238

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Physical Medicine & Rehabilitation, Neurobiology, and Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA

    Martin Oudega

  2. University of Pittsburgh School of Medicine, W1452 BSTWR, 200 Lothrop Street, Pittsburgh, PA 15213, USA

    Martin Oudega

Authors
  1. Martin Oudega
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Oudega.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oudega, M. Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair. Cell Tissue Res 349, 269–288 (2012). https://doi.org/10.1007/s00441-012-1440-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-012-1440-6

Keywords

Search

Navigation