Delayed administration of a bio-engineered zinc-finger VEGF-A gene therapy is neuroprotective and attenuates allodynia following traumatic spinal cord injury

PLoS ONE

Volumn 9, Issue 5, 2014, Pages

  Figley, Sarah A ^a,b   Liu, Yang ^a   Karadimas, Spyridon K ^a,b   Satkunendrarajah, Kajana ^a   Fettes, Peter ^a   Kaye Spratt, S ^c   Lee, Gary ^c   Ando, Dale ^c   Surosky, Richard ^c   Giedlin, Martin ^b   Fehlings, Michael G ^a,b  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c Department of Therapeutic Development Sangamo BioSciences ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; CYCLOSPORIN; MESSENGER RNA; VASCULOTROPIN A; ZINC FINGER PROTEIN; VASCULAR ENDOTHELIAL GROWTH FACTOR A, RAT;

ADULT; ALLODYNIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD VESSEL DIAMETER; CELL DEATH; CONTROLLED STUDY; FEMALE; IMMUNOSUPPRESSIVE TREATMENT; NEUROPROTECTION; NONHUMAN; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; RAT; REAL TIME POLYMERASE CHAIN REACTION; SPINAL CORD INJURY; VIRAL GENE THERAPY; WESTERN BLOTTING; ADENOVIRIDAE; ANGIOGENESIS; ANIMAL; BIOSYNTHESIS; COMPLICATION; GENE THERAPY; GENETICS; HEK293 CELL LINE; HUMAN; HYPERALGESIA; METABOLISM; PATHOLOGY; PROCEDURES; SPINAL CORD INJURIES; WISTAR RAT;

ADENOVIRIDAE; ANIMALS; FEMALE; GENETIC THERAPY; HEK293 CELLS; HUMANS; HYPERALGESIA; NEOVASCULARIZATION, PHYSIOLOGIC; RATS; RATS, WISTAR; SPINAL CORD INJURIES; VASCULAR ENDOTHELIAL GROWTH FACTOR A; ZINC FINGERS;

EID: 84901372372     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0096137     Document Type: Article

References (71)

1. Sekhon LH, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 26: S2-S12. (Pubitemid 34019773)
2. 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.
3. Beattie MS (2004) Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 10: 580-583.
4. Fehlings MG, Tator CH, Linden RD (1989) The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalogr Clin Neurophysiol 74: 241-259. (Pubitemid 19164308)
5. Leypold BG, Flanders AE, Schwartz ED, Burns AS (2007) The impact of methylprednisolone on lesion severity following spinal cord injury. Spine 32: 373-378; discussion 379-381.
6. 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. (Pubitemid 351214227)
7. Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359: 843-845.
8. Greenberg DA, Jin K (2005) From angiogenesis to neuropathology. Nature 438: 954-959. (Pubitemid 43093961)
9. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246: 1306-1309. (Pubitemid 20066716)
10. Waxman SG, Cummins TR, Dib-Hajj S, Fjell J, Black JA (1999) Sodium channels, excitability of primary sensory neurons, and the molecular basis of pain. Muscle & Nerve 22: 1177-1187. (Pubitemid 29409685)
11. Liu Y, Figley S, Spratt SK, Lee G, Ando D, et al. (2010) An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury. Neurobiology of Disease 37: 384-393.
12. Price SA, Dent C, Duran-Jimenez B, Liang Y, Zhang L, et al. (2006) Gene transfer of an engineered transcription factor promoting expression of VEGF-A protects against experimental diabetic neuropathy. Diabetes 55: 1847-1854. (Pubitemid 44324142)
13. Liu PQ, Rebar EJ, Zhang L, Liu Q, Jamieson AC, et al. (2001) Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. Activation of vascular endothelial growth factor A. J Biol Chem 276: 11323-11334. (Pubitemid 38089322)
14. Fehlings MG, Tator CH (1995) The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury. Exp Neurol 132: 220-228.
15. Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12: 1-21.
16. Koopmans GC, Deumens R, Honig WM, Hamers FP, Steinbusch HW, et al. (2005) The assessment of locomotor function in spinal cord injured rats: the importance of objective analysis of coordination. J Neurotrauma 22: 214-225. (Pubitemid 40333516)
17. Hamers FP, Koopmans GC, Joosten EA (2006) CatWalk-assisted gait analysis in the assessment of spinal cord injury. J Neurotrauma 23: 537-548. (Pubitemid 43726327)
18. Gensel JC, Tovar CA, Hamers FP, Deibert RJ, Beattie MS, et al. (2006) Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats. J Neurotrauma 23: 36-54. (Pubitemid 43191085)
19. Bruce JC, Oatway MA, Weaver LC (2002) Chronic pain after clip-compression injury of the rat spinal cord. Exp Neurol 178: 33-48. (Pubitemid 35425607)
20. Holm S (1979) A simple sequentially rejective multiple test procedure. Scandinavian Journal of Statistics 6: 65-70.
21. Glantz SA (2005) Primer of Biostatistics: McGraw-Hill Companies,Inc. 520 p.
22. Dai Q, Huang J, Klitzman B, Dong C, Goldschmidt-Clermont PJ, et al. (2004) Engineered zinc finger-activating vascular endothelial growth factor transcription factor plasmid DNA induces therapeutic angiogenesis in rabbits with hindlimb ischemia. Circulation 110: 2467-2475. (Pubitemid 39407355)
23. Rebar EJ, Huang Y, Hickey R, Nath AK, Meoli D, et al. (2002) Induction of angiogenesis in a mouse model using engineered transcription factors. Nat Med 8: 1427-1432. (Pubitemid 36019428)
24. Yu J, Lei L, Liang Y, Hinh L, Hickey RP, et al. (2006) An engineered VEGF-activating zinc finger protein transcription factor improves blood flow and limb salvage in advanced-age mice. Faseb J 20: 479-481. (Pubitemid 46671222)
25. Casha S, Yu WR, Fehlings MG (2001) Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 103: 203-218. (Pubitemid 32304360)
26. Schumacher PA, Siman RG, Fehlings MG (2000) Pretreatment with calpain inhibitor CEP-4143 inhibits calpain I activation and cytoskeletal degradation, improves neurological function, and enhances axonal survival after traumatic spinal cord injury. J Neurochem 74: 1646-1655. (Pubitemid 30163987)
27. Karimi-Abdolrezaee S, Eftekharpour E, Fehlings MG (2004) Temporal and spatial patterns of Kv1.1 and Kv1.2 protein and gene expression in spinal cord white matter after acute and chronic spinal cord injury in rats: implications for axonal pathophysiology after neurotrauma. Eur J Neurosci 19: 577-589. (Pubitemid 38241297)
28. Byrne AM, Bouchier-Hayes DJ, Harmey JH (2005) Angiogenic and cell survival functions of Vascular Endothelial Growth Factor (VEGF). Journal of Cellular and Molecular Medicine 9: 777-794. (Pubitemid 43116546)
29. Werhagen L, Budh CN, Hultling C, Molander C (2004) Neuropathic pain after traumatic spinal cord injury - relations to gender, spinal level, completeness, and age at the time of injury. Spinal Cord 42: 665-673. (Pubitemid 40065530)
30. Dijkers M, Bryce T, Zanca J (2009) Prevalence of chronic pain after traumatic spinal cord injury: A systematic review. Journal of Rehabilitation Research &Development 46: 13-30.
31. Nesic O, Sundberg LM, Herrera JJ, Mokkapati VUL, Lee J, et al. (2010) Vascular Endothelial Growth Factor and Spinal Cord Injury Pain. Journal of Neurotrauma 27: 1793-1803.
32. Sun Y, Jin K, Xie L, Childs J, Mao XO, et al. (2003) VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. The Journal of Clinical Investigation 111: 1843-1851. (Pubitemid 38057729)
33. Widenfalk J, Lipson A, Jubran M, Hofstetter C, Ebendal T, et al. (2003) Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience 120: 951-960. (Pubitemid 36966647)
34. Ling X, Liu D (2007) Temporal and spatial profiles of cell loss after spinal cord injury: Reduction by a metalloporphyrin. Journal of Neuroscience Research 85: 2175-2185. (Pubitemid 47172149)
35. Grossman SD, Rosenberg LJ, Wrathall JR (2001) Temporal-Spatial Pattern of Acute Neuronal and Glial Loss after Spinal Cord Contusion. Experimental Neurology 168: 273-282. (Pubitemid 32289763)
36. Liu XZ, Xu XM, Hu R, Du C, Zhang SX, et al. (1997) Neuronal and Glial Apoptosis after Traumatic Spinal Cord Injury. The Journal of Neuroscience 17: 5395-5406.
37. Loy DN, Crawford CH, Darnall JB, Burke DA, Onifer SM, et al. (2002) Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat. J Comp Neurol 445: 308-324. (Pubitemid 34252854)
38. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, et al. (2009) Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 29: 13435-13444.
39. Mabon PJ, Weaver LC, Dekaban GA (2000) Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Exp Neurol 166: 52-64.
40. Glaser J, Gonzalez R, Sadr E, Keirstead HS (2006) Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury. Journal of Neuroscience Research 84: 724-734. (Pubitemid 44366674)
41. Yoshihara T, Ohta M, Itokazu Y, Matsumoto N, Dezawa M, et al. (2007) Neuroprotective Effect of Bone Marrow - Derived Mononuclear Cells Promoting Functional Recovery from Spinal Cord Injury. Journal of Neurotrauma 24: 1026-1036. (Pubitemid 47015436)
42. Kaneko S, Iwanami A, Nakamura M, Kishino A, Kikuchi K, et al. (2006) A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nature Medicine 12: 1380-1389. (Pubitemid 44924496)
43. Ohab JJ, Fleming S, Blesch A, Carmichael ST (2006) A neurovascular niche for neurogenesis after stroke. Journal of Neuroscience 26: 13007-13016. (Pubitemid 44954619)
44. Raab S, Plate K (2007) Different networks, common growth factors: shared growth factors and receptors of the vascular and the nervous system. Acta Neuropathologica 113: 607-626. (Pubitemid 46863898)
45. Peters KG, De Vries C, Williams LT (1993) Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth. Proceedings of the National Academy of Sciences 90: 8915-8919. (Pubitemid 23306421)
46. Tsao MN, Li YQ, Lu G, Xu Y, Wong CS (1999) Upregulation of Vascular Endothelial Growth Factor Is Associated with Radiation-Induced Blood-Spinal Cord Barrier Breakdown. Journal of Neuropathology & Experimental Neurology 58: 1051-1060. (Pubitemid 29468266)
47. Skold MK, Gertten CV, Sandbergnordqvist A-C, Mathiesen T, Holmin S (2005) VEGF and VEGF Receptor Expression after Experimental Brain Contusion in Rat. Journal of Neurotrauma 22: 353-367. (Pubitemid 40434684)
48. Jin KL, Mao XO, Nagayama T, Goldsmith PC, Greenberg DA (2000) Induction of vascular endothelial growth factor and hypoxia-inducible factor-1α by global ischemia in rat brain. Neuroscience 99: 577-585. (Pubitemid 30612460)
49. Jin KL, Mao XO, Greenberg DA (2000) Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci U S A 97: 10242-10247.
50. Krum JM, Rosenstein JM (1998) VEGF mRNA and Its Receptor flt-1 Are Expressed in Reactive Astrocytes Following Neural Grafting and Tumor Cell Implantation in the Adult CNS. Experimental Neurology 154: 57-65. (Pubitemid 28553567)
51. Krum JM, Rosenstein JM (1999) Transient Coexpression of Nestin, GFAP, and Vascular Endothelial Growth Factor in Mature Reactive Astroglia Following Neural Grafting or Brain Wounds. Experimental Neurology 160: 348-360.
52. Neufeld G, Kessler O, Herzog Y (2003) The Interaction of Neuropilin-1 and Neuropilin-2 with Tyrosine-Kinase Receptors for VEGF. In: Bagnard D, editor: Springer US. pp. 81-90.
53. Neufeld G, Cohen T, Shraga N, Lange T, Kessler O, et al. (2002) The Neuropilins: Multifunctional Semaphorin and VEGF Receptors that Modulate Axon Guidance and Angiogenesis. Trends in Cardiovascular Medicine 12: 13-19. (Pubitemid 34048706)
54. Bearden SE, Segal SS (2004) Microvessels Promote Motor Nerve Survival and Regeneration Through Local VEGF Release Following Ectopic Reattachment. Microcirculation 11: 633-644. (Pubitemid 40012342)
55. Hobson MI, Green CJ, Terenghi G (2000) VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. Journal of Anatomy 197: 591-605. (Pubitemid 32051540)
56. Choi UH, Ha Y, Huang X, Park SR, Chung J, et al. (2007) Hypoxia-inducible expression of vascular endothelial growth factor for the treatment of spinal cord injury in a rat model. J Neurosurg Spine 7: 54-60. (Pubitemid 47067739)
57. Facchiano F, Fernandez E, Mancarella S, Maira G, Miscusi M, et al. (2002) 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 97: 161-168. (Pubitemid 34693714)
58. Benton RL, Whittemore SR (2003) VEGF165 therapy exacerbates secondary damage following spinal cord injury. Neurochem Res 28: 1693-1703. (Pubitemid 37296211)
59. Barleon B, Sozzani S, Zhou D, Weich H, Mantovani A, et al. (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87: 3336-3343. (Pubitemid 26115364)
60. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Morshead CM, Fehlings MG (2006) Delayed Transplantation of Adult Neural Precursor Cells Promotes Remyelination and Functional Neurological Recovery after Spinal Cord Injury. The Journal of Neuroscience 26: 3377-3389.
61. Yezierski RP, Liu S, Ruenes GL, Busto R, Dietrich WD (1996) Neuronal Damage Following Intraspinal Injection of a Nitric Oxide Synthase Inhibitor in the Rat. J Cereb Blood Flow Metab 16: 996-1004. (Pubitemid 26292068)
62. Azzouz M, Hottinger A, Paterna J-C, Zurn AD, Aebischer P, et al. (2000) Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2. Human Molecular Genetics 9: 803-811. (Pubitemid 30162765)
63. Naldini A, Carraro F (2005) Role of inflammatory mediators in angiogenesis. Curr Drug Targets Inflamm Allergy 4: 3-8. (Pubitemid 40584847)
64. Flynn JR, Graham BA, Galea MP, Callister RJ (2011) The role of propriospinal interneurons in recovery from spinal cord injury. Neuropharmacology 60: 809-822.
65. Pearse DD, Pereira FC, Marcillo AE, Bates ML, Berrocal YA, et al. (2004) cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nature Medicine 10: 610-616. (Pubitemid 38796852)
66. Ballermann M, Fouad K (2006) Spontaneous locomotor recovery in spinal cord injured rats is accompanied by anatomical plasticity of reticulospinal fibers. European Journal of Neuroscience 23: 1988-1996.
67. Defrin R, Ohry A, Blumen N, Urca G (2001) Characterization of chronic pain and somatosensory function in spinal cord injury subjects. Pain 89: 253-263. (Pubitemid 32146405)
68. Österberg A, Boivie J (2010) Central pain in multiple sclerosis - Sensory abnormalities. European Journal of Pain 14: 104-110.
69. Vierck Jr CJ, Siddall P, Yezierski RP (2000) Pain following spinal cord injury: animal models and mechanistic studies. Pain 89: 1-5.
70. Hoheisel U, Scheifer C, Trudrung P, Unger T, Mense S (2003) Pathophysiological activity in rat dorsal horn neurones in segments rostral to a chronic spinal cord injury. Brain Research 974: 134-145. (Pubitemid 36549227)
71. Schratzberger P, Walter DH, Rittig K, Bahlmann FH, Pola R, et al. (2001) Reversal of experimental diabetic neuropathy by VEGF gene transfer. The Journal of Clinical Investigation 107: 1083-1092. (Pubitemid 32422905)