Gene Therapy for Stroke

Chapter
First Online:
Part of the Translational Medicine Research book series (TRAMERE)

Abstract

Ischemic stroke is one of the leading causes of death in the world. Current treatment option is limited by therapeutic time window. Gene transfer might be a potential strategy to decrease neurologic dysfunction after stroke. In this chapter, we discussed status of gene therapy for ischemic stroke, available vectors, potential targets, therapeutic genes, and delivery methods.

Keywords

Angiogenesis Gene therapy Ischemic stroke Neuroprotection Vector 

Abbreviations

AAV

Adeno-associated virus

Ad

Adenoviral virus

ANG

Angiopoietins

BBB

Blood-brain barrier

BDNF

Brain-derived neurotrophic factor

CNS

Central nerve system

EGF

Epidermal growth factor

eNOS

Endothelial nitric oxide synthase

EPO

Erythropoietin

FGF

Fibroblast growth factors

G-CSF

Granulocyte colony-stimulating factor

GPE

Glycine-proline-glutamate

GSH peroxidase

Glutathione peroxidase

HO-1

Heme oxygenase-1

HREs

Hypoxia response elements

Hsp70

Heat-shock protein 70

HSV

Herpes simplex virus

IA

Intra-arterial

IGF-1

Insulin-like growth factor-1

iPSCs

Induced pluripotent stem cells

IV

Intravenous

MCAO

Middle cerebral artery occlusion

MHPs

Microglial healing peptides

miRNAs

MicroRNAs

MMLV

Melony murine leukemia virus

MMP

Matrix metalloproteinase

MSCs

Bone marrow mesenchymal stromal cells

NMDA

N-methyl-D-aspartate

Nox1

Nitrogen oxides

NSC

Neural stem cell

NT3

Neurotrophin-3

ODNs

Antisense oligodeoxynucleotides

PEG

Polyethylene glycol

PPE-EA

Polyaminoethyl propylene phosphate

RA-NP

Retinoic acid-loaded nanoparticles

ROS

Reactive oxygen species

RTL1000

T-cell receptor ligand 1000

rtPA

Recombinant tissue plasminogen activator

SGZ

Subgranular zone

SHR-SP

Stroke-prone spontaneously hypertensive rat

siRNAs

Small interference RNAs

SOD

Superoxide dismutase

SVZ

Subventricular zone

TAT

Transactivating transcriptional activator

TGF

Transforming growth factors

Th

Type-2 helper T cells

TJs

Tight junctions

VEGF

Vascular endothelial growth factor

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

References

  1. 1.
    Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(10):3020–35.PubMedCrossRefGoogle Scholar
  2. 2.
    Mishra NK, Lyden P, Grotta JC, Lees KR, VISTA Collaborators. Thrombolysis is associated with consistent functional improvement across baseline stroke severity: a comparison of outcomes in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke. 2010;41(11):2612–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375(9727):1695–703.PubMedCrossRefGoogle Scholar
  4. 4.
    Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004;363(9411):768–74.PubMedCrossRefGoogle Scholar
  5. 5.
    Wahlestedt C, Golanov E, Yamamoto S, Yee F, Ericson H, Yoo H, et al. Antisense oligodeoxynucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions. Nature. 1993;363(6426):260–3.PubMedCrossRefGoogle Scholar
  6. 6.
    Leng T, Shi Y, Xiong ZG, Sun D. Proton-sensitive cation channels and ion exchangers in ischemic brain injury: new therapeutic targets for stroke? Prog Neurobiol. 2014;115:189–209.PubMedCrossRefGoogle Scholar
  7. 7.
    Tuttolomondo A, Di Raimondo D, di Sciacca R, Pinto A, Licata G. Inflammatory cytokines in acute ischemic stroke. Curr Pharm Des. 2008;14(33):3574–89.PubMedCrossRefGoogle Scholar
  8. 8.
    Kim JY, Kawabori M, Yenari MA. Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets. Curr Med Chem. 2014;21(18):2076–97.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Globus MY, Busto R, Martinez E, Valdes I, Dietrich WD, Ginsberg MD. Comparative effect of transient global ischemia on extracellular levels of glutamate, glycine, and gamma-aminobutyric acid in vulnerable and nonvulnerable brain regions in the rat. J Neurochem. 1991;57(2):470–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci. 2003;4(5):399–415.PubMedCrossRefGoogle Scholar
  11. 11.
    Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22(9):391–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Jiang M, Li J, Peng Q, Liu Y, Liu W, Luo C, et al. Neuroprotective effects of bilobalide on cerebral ischemia and reperfusion injury are associated with inhibition of pro-inflammatory mediator production and down-regulation of JNK1/2 and p38 MAPK activation. J Neuroinflammation. 2014;11:167.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Ji K, Tsirka SE. Inflammation modulates expression of laminin in the central nervous system following ischemic injury. J Neuroinflammation. 2012;9:159.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Yu S, Wang C, Cheng Q, Xu H, Zhang S, Li L, et al. An active component of Achyranthes bidentata polypeptides provides neuroprotection through inhibition of mitochondrial-dependent apoptotic pathway in cultured neurons and in animal models of cerebral ischemia. PLoS One. 2014;9(10):e109923.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994;330(9):613–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Yu Z, Poppe JL, Wang X. Mitochondrial mechanisms of neuroglobin’s neuroprotection. Oxidative Med Cell Longev. 2013;2013:756989.CrossRefGoogle Scholar
  17. 17.
    Yun X, Maximov VD, Yu J, Zhu H, Vertegel AA, Kindy MS. Nanoparticles for targeted delivery of antioxidant enzymes to the brain after cerebral ischemia and reperfusion injury. J Cereb Blood Flow Metab. 2013;33(4):583–92.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Doeppner TR, Kaltwasser B, Fengyan J, Hermann DM, Bähr M. TAT-Hsp70 induces neuroprotection against stroke via anti-inflammatory actions providing appropriate cellular microenvironment for transplantation of neural precursor cells. J Cereb Blood Flow Metab. 2013;33(11):1778–88.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Nomoto T, Okada T, Shimazaki K, Yoshioka T, Nonaka-Sarukawa M, Ito T, et al. Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage instroke-prone spontaneously hypertensive rat. Gene Ther. 2009;16(3):383–91.PubMedCrossRefGoogle Scholar
  20. 20.
    Chao XD, Ma YH, Luo P, Cao L, Lau WB, Zhao BC, et al. Up-regulation of heme oxygenase-1 attenuates brain damage after cerebral ischemia via simultaneous inhibition of superoxide production and preservation of NO bioavailability. Exp Neurol. 2013;239:163–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Eum WS, Kim DW, Hwang IK, Yoo KY, Kang TC, Jang SH, et al. In vivo protein transduction: biologically active intact pep-1-superoxide dismutase fusion protein efficiently protects against ischemic insult. Free Radic Biol Med. 2004;37(10):1656–69.PubMedCrossRefGoogle Scholar
  22. 22.
    Brandes RP. Role of NADPH oxidases in the control of vascular gene expression. Antioxid Redox Signal. 2003;5:803–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke. 2009;4(6):461–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Song J, Park J, Oh Y, Lee JE. Glutathione suppresses cerebral infarct volume and cell death after ischemic injury: involvement of FOXO3 inactivation and Bcl2 expression. Oxidative Med Cell Longev. 2015;2015:426069.Google Scholar
  25. 25.
    Choi D-H, Kim J-H, Lee K-H, kim H-Y, Kim Y-S, Choi WS, et al. Role of neuronal NADPH oxidase 1 in the peri-infarct regions after stroke. PLoS One. 2015;10(1):e0116814.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Petro M, Jaffer H, Yang J, Kabu S, Morris VB, Labhasetwar V. Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain. Biomaterials. 2016;81:169–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87:779–89.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, et al. T- and B-cell deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab. 2007;27(11):1798–805.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Burrows GG, Chou YK, Wang C, Chang JW, Finn TP, Culbertson NE, et al. Rudimentary TCR signaling triggers default IL-10 secretion by human Th1 cells. J Immunol. 2001;167(8):4386–95.PubMedCrossRefGoogle Scholar
  30. 30.
    Zhu W, Dotson AL, Libal NL, Lapato AS, Bodhankar S, Offner H, et al. Recombinant T-cell receptor ligand RTL1000 limits inflammation and decreases infarct size after experimental ischemic stroke in middle-aged mice. Neuroscience. 2015;288:112–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Kurinami H, Shimamura M, Nakagami H, Shimizu H, Koriyama H, Kawano T, et al. A novel therapeutic peptide as a partial agonist of RANKL in ischemic stroke. Sci Rep. 2016.; 29;6:38062.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Ramos-Cejudo J, Gutiérrez-Fernández M, Otero-Ortega L, Rodríguez-Frutos B, Fuentes B, Vallejo-Cremades MT, et al. Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke. Stroke. 2015;46(1):221–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Ren J, Chen YI, Liu CH, Chen PC, Prentice H, Wu JY, et al. Noninvasive tracking of gene transcript and neuroprotection after gene therapy. Gene Ther. 2016;23(1):1–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Lau D, Bengtson CP, Buchthal B, Bading H. BDNF reduces toxic extrasynaptic NMDA receptor signaling via synaptic NMDA receptors and nuclear-calcium-induced transcription of inhba/activin a. Cell Rep. 2015;12(8):1353–66.PubMedCrossRefGoogle Scholar
  35. 35.
    Loddick SA, Liu XJ, Lu ZX, Liu C, Behan DP, Chalmers DC, et al. Displacement of insulin-like growth factors from their binding proteins as a potential treatment for stroke. Proc Natl Acad Sci U S A. 1998;95:1894–8.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Parker K, Berretta A, Saenger S, Sivaramakrishnan M, Shirley SA, Metzger F, et al. PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia. Sci Rep. 2017;7(1):241.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Zhu W, Fan Y, Hao Q, Shen F, Hashimoto T, Yang GY, et al. Postischemic IGF-1 gene transfer promotes neurovascular regeneration after experimental stroke. J Cereb Blood Flow Metab. 2009;29(9):1528–37.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Weissmiller AM, Wu C. Current advances in using neurotrophic factors to treat neurodegenerative disorders. Transl Neurodegener. 2012;1(1):14.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Airaksinen MS, Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci. 2002;3(5):383–94.PubMedCrossRefGoogle Scholar
  40. 40.
    Lohof AM, Nacy YIP, Poo M-M. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature. 1993;363(6427):350–3.PubMedCrossRefGoogle Scholar
  41. 41.
    Kuipers SD, Trentani A, Tiron A, Mao X, Kuhl D, Bramham CR. BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis. Sci Rep. 2016;6:21222.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Duricki DA, Hutson TH, Kathe C, Soleman S, Gonzalez-Carter D, Petruska JC, et al. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke. Brain. 2016;139(Pt 1):259–75.PubMedCrossRefGoogle Scholar
  43. 43.
    Fortun J, Puzis R, Pearse DD, Gage FH, Bunge MB. Muscle injection of AAV-NT3 promotes anatomical reorganization of CST axons and improves behavioral outcome following SCI. J Neurotrauma. 2009;26(7):941–53.PubMedCrossRefGoogle Scholar
  44. 44.
    Wang YQ, Cui HR, Yang SZ, Sun HP, Qiu MH, Feng XY, et al. VEGF enhance cortical newborn neurons and their neurite development in adult rat brain after cerebral ischemia. Neurochem Int. 2009;55(7):629–36.PubMedCrossRefGoogle Scholar
  45. 45.
    Hwang H, Jeong HS, Oh PS, Na KS, Kwon J, Kim J, et al. Improving cerebral blood flow through liposomal delivery of angiogenic peptides: potential of 18F-FDG PET imaging in ischemic stroke treatment. J Nucl Med. 2015;56(7):1106–11.PubMedCrossRefGoogle Scholar
  46. 46.
    Wang X, Zhang M, Feng R, Li WB, Ren SQ, Zhang J, et al. Physical exercise training and neurovascular unit in ischemic stroke. Neuroscience. 2014;271:99–107.PubMedCrossRefGoogle Scholar
  47. 47.
    Navarro-Sobrino M, Rosell A, Hernández-Guillamon M, Penalba A, Boada C, Domingues-Montanari S, et al. A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke. Atherosclerosis. 2011;216(1):205–11.PubMedCrossRefGoogle Scholar
  48. 48.
    Balseanu AT, Buga AM, Catalin B, Wagner DC, Boltze J, Zagrean AM, et al. Multimodal approaches for regenerative stroke therapies: combination of granulocyte colony-stimulating factor with bone marrow mesenchymal stem cells is not superior to G-CSF alone. Front Aging Neurosci. 2014;6:130.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Wolf WA, Martin JL, Kartje GL, Farrer RG. Evidence for fibroblast growth factor-2 as a mediator of amphetamine-enhanced motor improvement following stroke. PLoS One. 2014;9(9):e108031.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Góra-Kupilas K, Jośko J. The neuroprotective function of vascular endothelial growth factor (VEGF). Folia Neuropathol. 2005;43(1):31–9.PubMedGoogle Scholar
  51. 51.
    Zechariah A, ElAli A, Doeppner TR, Jin F, Hasan MR, Helfrich I, et al. Vascular endothelial growth factor promotes pericyte coverage of brain capillaries, improves cerebral blood flow during subsequent focal cerebral ischemia, and preserves the metabolic penumbra. Stroke. 2013;44(6):1690–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Lahiani A, Zahavi E, Netzer N, Ofir R, Pinzur L, Raveh S, et al. Human placental eXpanded (PLX) mesenchymal-like adherent stromal cells confer neuroprotection to nerve growth factor (NGF)-differentiated PC12 cells exposed to ischemia by secretion of IL-6 and VEGF. Biochim Biophys Acta. 2015;1853(2):422–30.PubMedCrossRefGoogle Scholar
  53. 53.
    Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M, et al. Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ Res. 1998;83(3):233–40.PubMedCrossRefGoogle Scholar
  54. 54.
    Shen F, Walker EJ, Jiang L, Degos V, Li J, Sun B, et al. Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood-brain barrier and reduces atrophy volume. J Cereb Blood Flow Metab. 2011;31(12):2343–51.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Leinninger GM, Feldman EL. Insulin-like growth factors in the treatment of neurological disease. Endocr Dev. 2005;9:135–59.PubMedCrossRefGoogle Scholar
  56. 56.
    Zhu W, Fan Y, Frenzel T, Gasmi M, Bartus RT, Young WL, et al. Insulin growth factor-1 gene transfer enhances neurovascular remodeling and improves long-term stroke outcome in mice. Stroke. 2008;39(4):1254–61.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Ribatti D, Nico B, Crivellato E. Morphological and molecular aspects of physiological vascular morphogenesis. Angiogenesis. 2009;12(2):101–11.PubMedCrossRefGoogle Scholar
  58. 58.
    Greenberg DA. Cerebral angiogenesis: a realistic therapy for ischemic disease? Methods Mol Biol. 2014;1135:21–4.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Gage FH, Coates PW, Palmer TD, Kuhn HG, Fisher LJ, Suhonen JO, et al. Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci U S A. 1995;92(25):11879–83.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, et al. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A. 2001;98(8):4710–5.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Trejo JL, Carro E, Torres-Aleman I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci. 2001;21(5):1628–34.PubMedGoogle Scholar
  62. 62.
    Carlson SW, Madathil SK, Sama DM, Gao X, Chen J, Saatman KE. Conditional overexpression of insulin-like growth factor-1 enhances hippocampal neurogenesis and restores immature neuron dendritic processes after traumatic brain injury. J Neuropathol Exp Neurol. 2014;73(8):734–46.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Bishop CJ, Majewski RL, Guiriba TM, Wilson DR, Bhise NS, Quiñones-Hinojosa A, et al. Quantification of cellular and nuclear uptake rates of polymeric gene delivery nanoparticles and DNA plasmids via flow cytometry. Acta Biomater. 2016;37:120–30.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Sebestyen MG, Hegge JO, Noble MA, Lewis DL, Herweijer H, Wolff JA. Progress toward a nonviral gene therapy protocol for the treatment of anemia. Hum Gene Ther. 2007;18(3):269–85.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Anan M, Abe T, Matsuda T, Ishii K, Kamida T, Fujiki M, et al. Induced angiogenesis under cerebral ischemia by cyclooxygenase 2 and hypoxia-inducible factor naked DNA in a rat indirect-bypass model. Neurosci Lett. 2006;409(2):118–23.PubMedCrossRefGoogle Scholar
  66. 66.
    Matsuda T, Abe T, Wu JL, Fujiki M, Kobayashi H. Hypoxia-inducible factor-1alpha DNA induced angiogenesis in a rat cerebral ischemia model. Neurol Res. 2005;27(5):503–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Ding H, Sagar V, Agudelo M, Pilakka-Kanthikeel S, Atluri VS, Raymond A, et al. Enhanced blood-brain barrier transmigration using a novel transferrin embedded fluorescent magneto-liposome nanoformulation. Nanotechnology. 2014;25(5):055101.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Reddy MK, Labhasetwar V. Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury. FASEB J. 2009;23(5):1384–95.PubMedCrossRefGoogle Scholar
  69. 69.
    Wang Z, Zhao Y, Jiang Y, Lv W, Wu L, Wang B, et al. Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system. Sci Rep. 2015;5:12651.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, et al. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987;84(21):7413–7.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Nikan M, Osborn MF, Coles AH, Godinho BM, Hall LM, Haraszti RA, et al. Docosahexaenoic acid conjugation enhances distribution and safety of siRNA upon local Administration in Mouse Brain. Mol Ther Nucleic Acids. 2016;5:e344.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Chelluboina B, Warhekar A, Dillard M, Klopfenstein JD, Pinson DM, Wang DZ, et al. Post-transcriptional inactivation of matrix metalloproteinase-12 after focal cerebral ischemia attenuates brain damage. Sci Rep. 2015.; 8;5:9504.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Ferreira R, Fonseca MC, Santos T, Sargento-Freitas J, Tjeng R, Paiva F, et al. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia. Nanoscale. 2016;8(15):8126–37.PubMedCrossRefGoogle Scholar
  74. 74.
    Hecker JG. Non-viral, lipid-mediated DNA and mRNA gene therapy of the Central Nervous System (CNS): chemical-based transfection. Methods Mol Biol. 2016;1382:307–24.PubMedCrossRefGoogle Scholar
  75. 75.
    Niidome T, Huang L. Gene therapy progress and prospects: nonviral vectors. Gene Ther. 2002;9(24):1647–52.PubMedCrossRefGoogle Scholar
  76. 76.
    Cao YJ, Shibata T, Rainov NG. Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model. Gene Ther. 2002;9(6):415–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Jeon P, Choi M, Oh J, Lee M. Dexamethasone-conjugated polyamidoamine dendrimer for delivery of the heme oxygenase-1 gene into the ischemic brain. Macromol Biosci. 2015;15(7):1021–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Li Y, Wang J, Lee CG, Wang CY, Gao SJ, Tang GP, et al. CNS gene transfer mediated by a novel controlled release system based on DNA complexes of degradable polycation PPE-EA: a comparison with polyethylenimine/DNA complexes. Gene Ther. 2004;11(1):109–14.PubMedCrossRefGoogle Scholar
  79. 79.
    Kumarswamy R, Thum T. Non-coding RNAs in cardiac remodeling and heart failure. Circ Res. 2013;113(6):676–89.PubMedCrossRefGoogle Scholar
  80. 80.
    Zhang W, Liu J, Hu X, Li P, Leak RK, Gao Y, et al. N-3 polyunsaturated fatty acids reduce neonatal hypoxic/ischemic brain injury by promoting phosphatidylserine formation and Akt signaling. Stroke. 2015;46(10):2943–50.PubMedCrossRefGoogle Scholar
  81. 81.
    Mehta SL, Kim T, Vemuganti R. Long noncoding RNA FosDT promotes ischemic brain injury by interacting with REST-associated chromatin-modifying proteins. J Neurosci. 2015;35(50):16443–9.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Stalmans S, Bracke N, Wynendaele E, Gevaert B, Peremans K, Burvenich C, et al. Cell-penetrating peptides selectively cross the blood-brain barrier in vivo. PLoS One. 2015;10(10):e0139652.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Zhou HH, Zhang AX, Zhang Y, Zhu DY. Cloning, expression, and purification of a recombinant Tat-HA-NR2B9c peptide. Protein Expr Purif. 2012;85(2):239–45.PubMedCrossRefGoogle Scholar
  84. 84.
    Zhu Y, Bu Q, Liu X, Hu W, Wang Y. Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats. PLoS One. 2014;9(3):e93334.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Wang X, Pei L, Yan H, Wang Z, Wei N, Wang S, et al. Intervention of death-associated protein kinase 1-p53 interaction exerts the therapeutic effects against stroke. Stroke. 2014;45(10):3089–91.PubMedCrossRefGoogle Scholar
  86. 86.
    Lee J, Hyun H, Kim J, Ryu JH, Kim HA, Park JH, et al. Dexamethasone-loaded peptide micelles for delivery of the heme oxygenase-1 gene to ischemic brain. J Control Release. 2012;158(1):131–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Zhang H, Yang B, Mu X, Ahmed SS, Su Q, He R, Wang H, Mueller C, Sena-Esteves M, Brown R, Xu Z, Gao G. Several rAAV vectors efficiently cross the blood-brain barrier and transduce neurons and astrocytes in the neonatal mouse central nervous system. Mol Ther. 2011 Aug;19(8):1440–8Google Scholar
  88. 88.
    Saha B, Wong CM, Parks RJ. The adenovirus genome contributes to the structural stability of the virion. Virus. 2014;6(9):3563–83.CrossRefGoogle Scholar
  89. 89.
    Carter BJ. Adeno- associated viral vector. Curr Opin Biotechnol. 1992;3(5):533–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Kaplitt MG, Leone P, Samulski RJ, Xiao X, Pfaff DW, O’Malley KL, et al. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet. 1994;8(2):148–54.PubMedCrossRefGoogle Scholar
  91. 91.
    Wang C, Wang CM, Clark KR, Sferra TJ. Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain. Gene Ther. 2004;10(17):1528–34.CrossRefGoogle Scholar
  92. 92.
    Xiao X, Li J, Samulski RJ. Efficient long-term gene transfer into muscle tissue of immunocopetent mice by adeno-associated virus vector. J Virol. 1996;70(11):8098–108.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Shen F, Su H, Liu W, Kan YW, Young WL, Yang GY. Recombinant adeno-associated viral vector encoding human VEGF165 induces neomicrovessel formation in the adult mouse brain. Front Biosci. 2006;11(1):3190–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. VEGF gene delivery to myocardium: deleterious effects of unregulated expression. Circulation. 2000;102(8):898–901.PubMedCrossRefGoogle Scholar
  95. 95.
    Shen F, Su H, Fan Y, Chen Y, Zhu Y, Liu W, et al. Adeno-associated viral-vector-mediated hypoxia-inducible vascular endothelial growth factor gene expression attenuates ischemic brain injury after focal cerebral ischemia in mice. Stroke. 2006;37(10):2601–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Shen F, Kuo R, Milon-Camus M, Han Z, Jiang L, Young WL, et al. Intravenous delivery of adeno-associated viral vector serotype 9 mediates effective gene expression in ischemic stroke lesion and brain angiogenic foci. Stroke. 2013;44(1):252–4.PubMedCrossRefGoogle Scholar
  97. 97.
    Byrnes AP, Rusby JE, Wood MJ, Charlton HM. Adenovirus gene transfer causes inflammation in the brain. Neuroscience. 1995;66(4):1015–24.PubMedCrossRefGoogle Scholar
  98. 98.
    Zirger JM, Barcia C, Liu C, Puntel M, Mitchell N, Campbell I, et al. Rapid upregulation of interferon-regulated and chemokine mRNAs upon injection of 108 international units, but not lower doses, of adenoviral vectors into the brain. J Virol. 2006;80(11):5655–9.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Li ST, Pan J, Hua XM, Liu H, Shen S, Liu JF, et al. Endothelial nitric oxide synthase protects neurons against ischemic injury through regulation of brain-derived neurotrophic factor expression. CNS Neurosci Ther. 2014;20(2):154–64.PubMedCrossRefGoogle Scholar
  100. 100.
    Yoo J, Seo JJ, Eom JH, Hwang DY. Effects of stromal cell-derived factor 1α delivered at different phases of transient focal ischemia in rats. Neuroscience. 2012;209(3):171–86.PubMedCrossRefGoogle Scholar
  101. 101.
    Shi Q, Zhang P, Zhang J, Chen X, Lu H, Tian Y, et al. Adenovirus-mediated brain-derived neurotrophic factor expression regulated by hypoxia response element protects brain from injury of transient middle cerebral artery occlusion in mice. Neurosci Lett. 2009;465(3):220–5.PubMedCrossRefGoogle Scholar
  102. 102.
    Hu Q, Chen C, Khatibi NH, Li L, Yang L, Wang K, et al. Lentivirus-mediated transfer of MMP-9 shRNA provides neuroprotection following focal ischemic brain injury in rats. Brain Res. 2011;1367(7):347–59.PubMedCrossRefGoogle Scholar
  103. 103.
    Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010;363(4):355–64.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Lentz TB, Gray SJ, Samulski RJ. Viral vectors for gene delivery to the central nervous system. Neurobiol Dis. 2012;48(2):179–88.PubMedCrossRefGoogle Scholar
  105. 105.
    Yenari M, Minami M, Sun G, Meier TJ, Kunis DM, McLaughlin JR, et al. Calbindin D28K overexpression protects striatal neurons from transient focal cerebral ischemia. Stroke. 2001;32(4):1028–35.PubMedCrossRefGoogle Scholar
  106. 106.
    Davis AS, Zhao H, Sun GH, Sapolsky RM, Steinberg GK. Gene therapy using SOD1 protects striatal neurons from experimental stroke. Neurosci Lett. 2007;411(1):32–6.PubMedCrossRefGoogle Scholar
  107. 107.
    Masaki I, Yonemitsu Y, Komori K, Ueno H, Nakashima Y, Nakagawa K, et al. Recombinant Sendai virus-mediated gene transfer to vasculature: a new class of efficient genetransfer vector to the vascular system. FASEB J. 2001;15(7):1294–6.PubMedGoogle Scholar
  108. 108.
    Jin G, Inoue M, Hayashi T, Deguchi K, Nagotani S, Zhang H, et al. Sendai virus-mediated gene transfer of GDNF reduces AIF translocation and ameliorates ischemic cerebral injury. Neurol Res. 2008;30(7):731–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Shirakura M, Inoue M, Fujikawa S, Washizawa K, Komaba S, Maeda M, et al. Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils. Gene Ther. 2004;11(9):784–90.PubMedCrossRefGoogle Scholar
  110. 110.
    Paczkowska E, Larysz B, Rzeuski R, Karbicka A, Jałowiński R, Kornacewicz-Jach Z, et al. Human hematopoietic stem/progenitor-enriched CD34(+) cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction. Eur J Haematol. 2005;75(6):46–467.CrossRefGoogle Scholar
  111. 111.
    Yoo J, Kim HS, Seo JJ, Eom JH, Choi SM, Park S, et al. Therapeutic effects of umbilical cord blood plasma in a rat model of acute ischemic stroke. Oncotarget. 2016;7(48):79131–40.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Lee JY, Kim E, Choi SM, Kim DW, Kim KP, Lee I, et al. Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke. Sci Rep. 2016;6:33038.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Liang AC, Mandeville ET, Maki T, Shindo A, Som AT, Egawa N, et al. Effects of aging on neural stem/progenitor cells and oligodendrocyte precursor cells after focal cerebral ischemia in spontaneously hypertensive rats. Cell Transplant. 2016;25(4):705–14.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Bhasin A, Srivastava MV, Mohanty S, Vivekanandhan S, Sharma S, Kumaran S, et al. Paracrine mechanisms of intravenous bone marrow-derived mononuclear stem cells in chronic ischemic stroke. Cerebrovasc Dis Extra. 2016;6(3):107–19.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Cho GW, Koh SH, Kim MH, Yoo AR, Noh MY, Oh S, et al. The neuroprotective effect of erythropoietin-transduced human mesenchymal stromal cells in an animal model of ischemic stroke. Brain Res. 2010;1353:1–13.PubMedCrossRefGoogle Scholar
  116. 116.
    Tao J, Ji F, Liu B, Wang F, Dong F, Zhu Y. Improvement of deficits by transplantation of lentiviral vector-modified human amniotic mesenchymal cells after cerebral ischemia in rats. Brain Res. 2012;1448:1–10.PubMedCrossRefGoogle Scholar
  117. 117.
    Liu H, Honmou O, Harada K, Nakamura K, Houkin K, Hamada H, et al. Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia. Brain. 2006;129(Pt 10):2734–45.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Toyama K, Honmou O, Harada K, Suzuki J, Houkin K, Hamada H, et al. Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia. Exp Neurol. 2009;216(1):47–55.PubMedCrossRefGoogle Scholar
  119. 119.
    Ihrie RA, Alvarez-Buylla A. Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. Neuron. 2011;70(4):674–86.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Moshayedi P, Nih LR, Llorente IL, Berg AR, Cinkornpumin J, Lowry WE, et al. Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials. 2016;105:145–55.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Lam J, Lowry WE, Carmichael ST, Segura T. Delivery of iPS-NPCs to the stroke cavity within a hyaluronic acid matrix promotes the differentiation of transplanted cells. Adv Funct Mater. 2014;24(44):7053–62.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Tornero D, Wattananit S, Gronning Madsen M, Koch P, Wood J, Tatarishvili J, et al. Human induced pluripotent stem cell-derived cortical neurons integrate in stroke-injured cortex and improve functional recovery. Brain J Neurol. 2013;136(Pt 12):3561–77.CrossRefGoogle Scholar
  123. 123.
    Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004;16(1):1–13.PubMedCrossRefGoogle Scholar
  124. 124.
    Keaney J, Campbell M. The dynamic blood-brain barrier. FEBS J. 2015;282(21):4067–79.PubMedCrossRefGoogle Scholar
  125. 125.
    Banerjee S, Bentley P, Hamady M, Marley S, Davis J, Shlebak A, Habib N, Chataway J, et al. Intra-arterial immunoselected CD34+ stem cells for acute ischemic stroke. Stem Cells Transl Med. 2014;3(11):1322–30.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Gray SJ, Matagne V, Bachaboina L, Yadav S, Ojeda SR, Samulski RJ. Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates. Mol Ther. 2011;19(6):1058–69.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009;27(1):59–65.PubMedCrossRefGoogle Scholar
  128. 128.
    Duque S, Joussemet B, Riviere C, Marais T, Dubreil L, Douar AM, et al. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther. 2009;17(7):1187–96.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Foley CP, Rubin DG, Santillan A, Sondhi D, Dyke JP, Gobin YP, et al. Intra-arterial delivery of AAV vectors to the mouse brain after mannitol mediated blood brain barrier disruption. J Control Release. 2014;196:71–8.PubMedCrossRefGoogle Scholar
  130. 130.
    Neuwelt EA, Pagel MA, Dix RD. Delivery of ultraviolet-inactivated 35S-herpesvirus across an osmotically modified blood–brain barrier. J Neurosurg. 1991;74(3):475–9.PubMedCrossRefGoogle Scholar
  131. 131.
    Yoichi N, Masaya Y, Naho K, Yoko E-T, Sanae S, Norio T, et al. Enhancement of blood–brain barrier permeability and delivery of antisense oligonucleotides or plasmid DNA to the brain by the combination of bubble liposomes and high-intensity focused ultrasound. Pharmaceutics. 2015;7(3):344–62.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd.and Shanghai Jiao Tong University Press 2017

Authors and Affiliations

  1. 1.Department of Neurology & Institute of Neurology, Rui Jin and Rui Jin North HospitalShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Center for Cerebrovascular Research, Department of Anesthesia and Perioperative CareUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations