Endogenous repair signaling after brain injury and complementary bioengineering approaches to enhance neural regeneration

Biomarker Insights

Volumn 10, Issue , 2015, Pages 43-60

  Addington, Caroline P ^a   Roussas, Adam ^a   Dutta, Dipankar ^a   Stabenfeldt, Sarah E ^a  

^a Arizona State University   (United States)

Author keywords

Controlled release; Stem cells; Transplantation; Traumatic brain injury

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; EPIDERMAL GROWTH FACTOR; FIBROBLAST GROWTH FACTOR; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; STROMAL CELL DERIVED FACTOR 1ALPHA; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

ARTICLE; BIOENGINEERING; CELL PROLIFERATION; GENE OVEREXPRESSION; HUMAN; MICROENVIRONMENT; NERVE REGENERATION; NEURAL STEM CELL; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN METABOLISM; PROTEIN SECRETION; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; SUBGRANULAR ZONE; SUBVENTRICULAR ZONE; TISSUE SCAFFOLD; TRAUMATIC BRAIN INJURY; UPREGULATION;

EID: 84930685493     PISSN: None     EISSN: 11772719     Source Type: Journal    
DOI: 10.4137/BMIMI.S20062     Document Type: Article

References (267)

1. Thurman D, Guerrero J. Trends in hospitalization associated with traumatic brain injury. JAMA. 1999;282(10):954–7.
2. Coronado VG, McGuire LC, Sarmiento K, et al. Trends in traumatic brain injury in the U.S. and the public health response: 1995–2009. J Safety Res. 2012;43(4):299–307.
3. Arbour RB. Traumatic brain injury pathophysiology, monitoring, and mechanism-based care. Crit Care Nurs Clin North Am. 2013;25(2):297–319.
4. Selassie AW, Zaloshnja E, Langlois JA, Miller T, Jones P, Steiner C. Incidence of long-term disability following traumatic brain injury hospitalization, United States, 2003. J Head Trauma Rehabil. 2008;23(2):123–31.
5. Silver JM, McAllister TW, Yudofsky SC. Textbook of Traumatic Brain Injury. American Psychiatric Publishing, Inc., Arlington, VA; 2011.
6. Public Health Economics Program Eric A Finkelstein Senior Health Economist DHSSPRRTI, Economist NCIPCCDCPPSCSH, Scientist CTRMPR, Site Director Pacific Institute for Research, Evaluation M. Incidence and Economic Bur­den of Injuries in the United States. Oxford University Press, New York, NY; 2006.
7. McAllister TW. Neurobiological consequences of traumatic brain injury. Dia­logues Clin Neurosci. 2011;13(3):287.
8. McIntosh TK. Neurochemical sequelae of traumatic brain injury: therapeutic implications. Cerebrovasc Brain Metab Rev. 1994;6(2):109–62.
9. Hall ED, Sullivan PG, Gibson TR, Pavel KM, Thompson BM, Scheff SW. Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: more than a focal brain injury. J Neurotrauma. 2005;22(2):252–65.
10. Goldberg JS, Hirschi KK. Diverse roles of the vasculature within the neural stem cell niche. Regen Med. 2009;4(6):879–97.
11. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99(1):4–9.
12. Hayes RL, Jenkins LW, Lyeth BG. Neurotransmitter-mediated mechanisms of traumatic brain injury: acetylcholine and excitatory amino acids. J Neurotrauma. 1992;9:S173–87.
13. Parpura V, Haydon PG. Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons. Proc Natl Acad Sci U S A. 2000;97(15):8629–34.
14. Morganti-Kossmann MC, Rancan M, Otto VI, Stahel PF, Kossmann T. Role of cerebral inflammation after traumatic brain injury: a revisited concept. Shock. 2001;16(3):165–77.
15. Ziebell JM, Morganti-Kossmann MC. Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neu­rotherapeutics. 2010;7(1):22–30.
16. Hicks RR, Martin VB, Zhang L, Seroogy KB. Mild experimental brain injury differentially alters the expression of neurotrophin and neurotrophin receptor mRNAs in the hippocampus. Exp Neurol. 1999;160(2):469–78.
17. Barone FC, Kilgore KS. Role of inflammation and cellular stress in brain injury and central nervous system diseases. Clin Neurosci Res. 2006;6(5):329–56.
18. Helmy A, De Simoni M-G, Guilfoyle MR, Carpenter KL, Hutchinson PJ. Progress in neurobiology. Prog Neurobiol. 2011;95(3):352–72.
19. Palmer TD, Takahashi J, Gage FH. The adult rat hippocampus contains primor­dial neural stem cells. Mol Cell Neurosci. 1997;8(6):389–404.
20. Altman J, Das GD. Postnatal neurogenesis in the guinea-pig. Nature. 1967;214:1098–101.
21. Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 1996;16(6):2027–33.
22. Lois C, Alvarez-Buylla A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A. 1993;90(5):2074–77.
23. Doetsch F, Garca-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci. 1997;17(13):5046–61.
24. Tavazoie M, Van der Veken L, Silva-Vargas V, et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 2008;3(3):279–88.
25. Shen Q, Wang Y, Kokovay E, et al. Adult SVZ stem cells lie in a vascu­lar niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell. 2008;3(3):289–300.
26. Doetsch F. A niche for adult neural stem cells. Curr Opin Genet Dev. 2003;13(5):543–50.
27. Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell. 2008;3(3):265–78.
28. Shen Q, Goderie SK, Jin L, et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004;304(5675):1338–40.
29. Faigle R, Song H. Signaling mechanisms regulating adult neural stem cells and neurogenesis. Biochim Biophys Acta. 2013;1830(2):2435–48.
30. Jacques TS, Relvas JB, Nishimura S, Pytela R, Edwards GM, Streuli CH. Neural precursor cell chain migration and division are regulated through different beta1 integrins. Development. 1998;125(16):3167–77.
31. Ramaswamy S, Goings GE, Soderstrom KE, Szele FG, Kozlowski DA. Cellular proliferation and migration following a controlled cortical impact in the mouse. Brain Res. 2005;1053(1–2):38–53.
32. Chirumamilla S, Sun D, Bullock MR, Colello RJ. Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J Neurotrauma. 2002;19(6):693–703.
33. Thomsen GM, Le Belle JE, Harnisch JA, et al. Traumatic brain injury reveals novel cell lineage relationships within the subventricular zone. Stem Cell Res. 2014;13(1):48–60.
34. Zhang R, Zhang Z, Wang L, et al. Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct bound­ary in adult rats. J Cereb Blood Flow Metab. 2004;24(4):441–8.
35. Ninomiya M, Yamashita T, Araki N, Okano H, Sawamoto K. Enhanced neu­rogenesis in the ischemic striatum following EGF-induced expansion of transit-amplifying cells in the subventricular zone. Neurosci Lett. 2006;403(1–2):63–7.
36. Zhang RL, Chopp M, Gregg SR, et al. Patterns and dynamics of subventricular zone neuroblast migration in the ischemic striatum of the adult mouse. J Cereb Blood Flow Metab. 2009;29(7):1240–50.
37. Yamashita T. Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci. 2006;26(24):6627–36.
38. Bovetti S, Hsieh YC, Bovolin P, Perroteau I, Kazunori T, Puche AC. Blood ves­sels form a scaffold for neuroblast migration in the adult olfactory bulb. J Neurosci. 2007;27(22):5976–80.
39. Kokovay E, Goderie S, Wang Y, et al. Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell. 2010;7(2):163–73.
40. Hatic H, Kane MJ, Saykally JN, Citron BA. Modulation of transcription factor Nrf2 in an in vitro model of traumatic brain injury. J Neurotrauma. 2012;29(6):1188–96.
41. Iadecola C, Salkowski CA, Zhang F, et al. The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to isch­emic brain injury. J Exp Med. 1999;189(4):719–27.
42. Li A, Sun X, Ni Y, Chen X, Guo A. HIF-1α involves in neuronal apoptosis after traumatic brain injury in adult rats. J Mol Neurosci. 2013;51(3):1052–62.
43. Ramos-Cejudo J, Gutiérrez-Fernández M, Rodríguez-Frutos B, et al. Spatial and temporal gene expression differences in core and periinfarct areas in experi­mental stroke: a microarray analysis. PLoS ONE. 2012;7(12):e52121.
44. Itoh T, Satou T, Ishida H, et al. The relationship between SDF-1 α/CXCR4 and neural stem cells appearing in damaged area after traumatic brain injury in rats. Neurol Res. 2009;31(1):90–102.
45. Xu Q, Wang S, Jiang X, et al. Hypoxia-induced astrocytes promote the migra­tion of neural progenitor cells via vascular endothelial factor, stem cell factor, stromal-derived factor-1? And monocyte chemoattractant protein-1 upregula­tion in vitro. Clin Exp Pharmacol Physiol. 2007;34(7):624–31.
46. Imitola J, Raddassi K, Park KI, et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine recep­tor 4 pathway. Proc Natl Acad Sci U S A. 2004;101(52):18117–22.
47. Hill WD, Hess DC, Martin-Studdard A, et al. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol. 2004;63(1):84–96.
48. Addington CP, Pauken CM, Caplan MR, Stabenfeldt SE. The role of SDF-1α-ECM crosstalk in determining neural stem cell fate. Biomaterials. 2014;35(10):3263–72.
49. Xue L, Wang J, Wang W, et al. The effect of stromal cell-derived factor 1 in the migration of neural stem cells. Cell Biochem Biophys. 2014;70(3):1609–16.
50. Filippo TR, Galindo LT, Barnabe GF, et al. CXCL12 N-terminal end is suffi­cient to induce chemotaxis and proliferation of neural stem/progenitor cells. Stem Cell Res. 2013;11(2):913–25.
51. Thored P, Arvidsson A, Cacci E, et al. Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells. 2006;24(3):739–47.
52. Nag S, Takahashi JL, Kilty DW. Role of vascular endothelial growth factor in blood-brain barrier breakdown and angiogenesis in brain trauma. J Neuropathol Exp Neurol. 1997;56(8):912–21.
53. Chodobski A, Chung I, Koźniewska E, et al. Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injury. Neuroscience. 2003;122(4):853–67.
54. Sköld MK, Gertten CV, Sandbergnordqvist A-C, Mathiesen T, Holmin S. VEGF and VEGF receptor expression after experimental brain contusion in rat. J Neurotrauma. 2005;22(3):353–67.
55. Krum JM, Rosenstein JM. VEGF mRNA and its receptor flt-1 are expressed in reactive astrocytes following neural grafting and tumor cell implantation in the adult CNS. Exp Neurol. 1998;154(1):57–65.
56. Papavassiliou E, Gogate N, Proescholdt M, et al. Vascular endothelial growth factor (vascular permeability factor) expression in injured rat brain. J Neurosci Res. 1997;49(4):451–60.
57. Mani N, Khaibullina A, Krum JM, Rosenstein JM. Vascular endothelial growth factor enhances migration of astroglial cells in subventricular zone neurosphere cultures. J Neurosci Res. 2010;88(2):248–57.
58. Schmidt NO, Koeder D, Messing M, et al. Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche. Brain Res. 2009;1268:24–37.
59. Zhang H. VEGF is a chemoattractant for FGF-2-stimulated neural progenitors. J Cell Biol. 2003;163(6):1375–84.
60. Wang Y, Jin K, Mao XO, et al. VEGF-overexpressing transgenic mice show enhanced post-ischemic neurogenesis and neuromigration. J Neurosci Res. 2007;85(4):740–7.
61. Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A. 2002;99(18):11946–50.
62. Schänzer A, Wachs FP, Wilhelm D, et al. Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. Brain Pathol. 2004;14(3):237–48.
63. Kawahara N, Mishima K, Higashiyama S, Taniguchi N, Tamura A, Kirino T. The gene for heparin-binding epidermal growth factor-like growth factor is stress-inducible: its role in cerebral ischemia. J Cereb Blood Flow Metab. 1999;19(3):307–20.
64. Doetsch F, Petreanu L, Caille I, Garcia-Verdugo JM, Alvarez-Buylla A. EGF converts transit-amplifying neurogenic precursors in the adult brain into multi­potent stem cells. Neuron. 2002;36(6):1021–34.
65. Reynolds BA, Tetzlaff W, Weiss S. A multipotent EGF-responsive stri­atal embryonic progenitor cell produces neurons and astrocytes. J Neurosci. 1992;12(11):4565–74.
66. Alagappan D, Lazzarino DA, Felling RJ, Balan M, Kotenko SV, Levison SW. Brain injury expands the numbers of neural stem cells and progenitors in the SVZ by enhancing their responsiveness to EGF. ASN Neuro. 2009;1(2):95–111.
67. Oyagi A, Morimoto N, Hamanaka J, et al. Forebrain specific heparin-binding epidermal growth factor-like growth factor knockout mice show exacerbated ischemia and reperfusion injury. Neuroscience. 2011;185:116–24.
68. Cook JL, Marcheselli V, Alam J, Deininger PL, Bazan NG. Temporal changes in gene expression following cryogenic rat brain injury. Brain Res Mol Brain Res. 1998;55(1):9–19.
69. Frautschy SA, Walicke PA, Baird A. Localization of basic fibroblast growth fac­tor and its mRNA after CNS injury. Brain Res. 1991;553(2):291–9.
70. Logan A, Frautschy SA, Gonzalez A-M, Baird A. A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci. 1992;12(10):3828–37.
71. Logan A, Frautschy SA, Baird A. Basic fibroblast growth factor and central ner­vous system injury. Ann N Y Acad Sci. 1991;638(1):474–6.
72. Finklestein SP, Apostolides PJ, Caday CG, Prosser J, Philips MF, Klagsbrun M. Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds. Brain Res. 1988;460(2):253–9.
73. Gritti A, Parati EA, Cova L, et al. Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth fac­tor. J Neurosci. 1996;16(3):1091–100.
74. Yoshimura S, Takagi Y, Harada J, et al. FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci U S A. 2001;98(10):5874–9.
75. Agasse F, Nicoleau C, Petit J, et al. Evidence for a major role of endogenous fibroblast growth factor-2 in apoptotic cortex-induced subventricular zone cell proliferation. Eur J Neurosci. 2007;26(11):3036–42.
76. Lindvall O, Ernfors P, Bengzon J, et al. Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma. Proc Natl Acad Sci U S A. 1992;89(2):648–52.
77. Truettner J, Schmidt-Kastner R, Busto R, et al. Expression of brain-derived neu­rotrophic factor, nerve growth factor, and heat shock protein HSP70 following fluid percussion brain injury in rats. J Neurotrauma. 2015;16(6):471–86.
78. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol. 2000;164(2):247–56.
79. Hicks RR, Numan S, Dhillon HS, Prasad MR, Seroogy KB. Alterations in BDNF and NT-3 mRNAs in rat hippocampus after experimental brain trauma. Brain Res Mol Brain Res. 1997;48(2):401–6.
80. Shetty AK, Rao MS, Hattiangady B, Zaman V, Shetty GA. Hippocampal neu­rotrophin levels after injury: relationship to the age of the hippocampus at the time of injury. J Neurosci Res. 2004;78(4):520–32.
81. Batchelor PE, Liberatore GT, Wong JY, et al. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci. 1999;19(5):1708–16.
82. Sieber-Blum M. Role of the neurotrophic factors BDNF and NGF in the com­mitment of pluripotent neural crest cells. Neuron. 1991;6(6):949–55.
83. Cheng A, Wang S, Cai J, Rao MS, Mattson MP. Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. Dev Biol. 2003;258(2):319–33.
84. Ahmed S, Reynolds BA, Weiss S. BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors. J Neurosci. 1995;15(8):5765–78.
85. Lachyankar MB, Condon PJ, Quesenberry PJ, Litofsky NS, Recht LD, Ross AH. Embryonic precursor cells that express Trk receptors: induction of different cell fates by NGF, BDNF, NT-3, and CNTF. Exp Neurol. 1997;144(2):350–60.
86. Kirschenbaum B, Goldman SA. Brain-derived neurotrophic factor promotes the survival of neurons arising from the adult rat forebrain subependymal zone. Proc Natl Acad Sci U S A. 1995;92(1):210–4.
87. Gao X, Chen J. Conditional knockout of brain-derived neurotrophic factor in the hippocampus increases death of adult-born immature neurons following traumatic brain injury. J Neurotrauma. 2009;26:1325–35.
88. Endres M, Fan G, Hirt L, et al. Ischemic brain damage in mice after selec­tively modifying BDNF or NT4 gene expression. J Cereb Blood Flow Metab. 2000;20(1):139–44.
89. Herx LM, Rivest S, Yong VW. Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 is required for the production of ciliary neu­rotrophic factor. J Immunol. 2000;165(4):2232–9.
90. Folkersma H, Brevé JJ, Tilders FJ, Cherian L, Robertson CS, Vandertop WP. Cerebral microdialysis of interleukin (IL)-1ß and IL-6: extraction efficiency and production in the acute phase after severe traumatic brain injury in rats. Acta Neurochir (Wien). 2008;150(12):1277–84.
91. Taupin V, Toulmond S, Serrano A, Benavides J, Zavala F. Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion: influence of pre-and post-traumatic treatment with Ro5 4864, a peripheral-type (p site) benzodiazepine ligand. J Neuroimmunol. 1993;42(2):177–85.
92. Harting MT, Jimenez F, Adams SD, Mercer DW, Cox CS Jr. Acute, regional inflammatory response after traumatic brain injury: implications for cellular therapy. Surgery. 2008;144(5):803–13.
93. Shojo H, Kaneko Y, Mabuchi T, Kibayashi K, Adachi N, Borlongan CV. Genetic and histologic evidence implicates role of inflammation in traumatic brain injury-induced apoptosis in the rat cerebral cortex following moderate fluid percussion injury. Neuroscience. 2010;171(4):1273–82.
94. Maegele M, Sauerland S, Bouillon B, et al. Differential immunoresponses following experimental traumatic brain injury, bone fracture and “two-hit-” combined neurotrauma. Inflamm Res. 2007;56(8):318–23.
95. Fassbender K, Schneider S, Bertsch T, et al. Temporal profile of release of interleukin-1βin neurotrauma. Neurosci Lett. 2000;284(3):135–8.
96. Woodroofe MN, Sarna GS, Wadhwa M, et al. Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdi­alysis: evidence of a role for microglia in cytokine production. J Neuroimmunol. 1991;33(3):227–36.
97. Koo JW, Duman RS. IL-1 beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci U S A. 2008;105(2):751–6.
98. Nolan Y, Martin D, Campbell VA, Lynch MA. Evidence of a protective effect of phosphatidylserine-containing liposomes on lipopolysaccharide-induced impairment of long-term potentiation in the rat hippocampus. J Neuroimmunol. 2004;151(1–2):12–23.
99. Arguello AA, Fischer SJ, Schonborn JR, Markus RW, Brekken RA, Eisch AJ. Effect of chronic morphine on the dentate gyrus neurogenic microenvironment. Neuroscience. 2009;159(3):1003–10.
100. Ben-Hur T, Ben-Menachem O, Furer V, Einstein O, Mizrachi-Kol R, Grigoriadis N. Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells. Mol Cell Neurosci. 2003;24(3):623–31.
101. Wang X, Fu S, Wang Y, et al. Interleukin-1βmediates proliferation and differ­entiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway. Mol Cell Neurosci. 2007;36(3):343–54.
102. Green HF, Treacy E, Keohane AK, Sullivan AM, O’Keeffe GW, Nolan YM. Molecular and cellular neuroscience. Mol Cell Neurosci. 2012;49(3):311–21.
103. Shohami E, Novikov M, Bass R, Yamin A, Gallily R. Closed-head injury trig­gers early production of Tnf-alpha and Il-6 by brain-tissue. J Cereb Blood Flow Metab. 1994;14(4):615–9.
104. Semple BD, Bye N, Ziebell JM, Morganti-Kossmann MC. Neurobiology of disease. Neurobiol Dis. 2010;40(2):394–403.
105. Stover JF, Schöning B, Beyer TF, Woiciechowsky C, Unterberg AW. Tempo­ral profile of cerebrospinal fluid glutamate, interleukin-6, and tumor necrosis factor-α in relation to brain edema and contusion following controlled cortical impact injury in rats. Neurosci Lett. 2000;288(1):25–8.
106. Buttini M, Appel K, Sauter A, Gebicke-Haerter P-J, Boddeke H. Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience. 1996;71(1):1–16.
107. Ahn M-J, Sherwood ER, Prough DS, Lin CY, DeWitt DS. The effects of trau­matic brain injury on cerebral blood flow and brain tissue nitric oxide levels and cytokine expression. J Neurotrauma. 2004;21(10):1431–42.
108. Kita T, Liu L, Tanaka N, Kinoshita Y. The expression of tumor necrosis factor-α in the rat brain after fluid percussive injury. Int J Legal Med. 1997;110(6):305–11.
109. Quintana A, Giralt M, Rojas S, et al. Differential role of tumor necrosis fac­tor receptors in mouse brain inflammatory responses in cryolesion brain injury. J Neurosci Res. 2005;82(5):701–16.
110. Iosif RE. Tumor necrosis factor receptor 1 is a negative regulator of progenitor pro­liferation in adult hippocampal neurogenesis. J Neurosci. 2006;26(38):9703–12.
111. Bernardino L. Modulator effects of interleukin-1 and tumor necrosis factor- on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures. J Neurosci. 2005;25(29):6734–44.
112. Widera D, Mikenberg I, Elvers M, Kaltschmidt C, Kaltschmidt B. Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling. BMC Neurosci. 2006;7:64.
113. Cacci E, Ajmone-Cat MA, Anelli T, Biagioni S, Minghetti L. In vitro neu­ronal and glial differentiation from embryonic or adult neural precursor cells are differently affected by chronic or acute activation of microglia. Glia. 2008;56(4):412–25.
114. Clausen F, Hånell A, Israelsson C, et al. Neutralization of interleukin-1βreduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice. Eur J Neurosci. 2011;34(1):110–23.
115. Godbout JP, Johnson RW. Interleukin-6 in the aging brain. J Neuroimmunol. 2004;147(1–2):141–4.
116. Suzuki S, Tanaka K, Suzuki N. Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophic aspects. J Cereb Blood Flow Metab. 2008;29(3):464–79.
117. Chiaretti A, Genovese O, Aloe L, et al. Interleukin 1βand interleukin 6 rela­tionship with paediatric head trauma severity and outcome. Childs Nerv Syst. 2004;21(3):185–93.
118. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003;302(5651):1760–5.
119. Vallieres L, CAMPBELL IL, Gage FH, Sawchenko PE. Reduced hippocam­pal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin−6. J Neurosci. 2002;22(2):486–92.
120. McPherson CA, Aoyama M, Harry GJ. Brain, behavior, and immunity. Brain Behav Immun. 2011;25(5):850–62.
121. Nakanishi M, Niidome T, Matsuda S, Akaike A, Kihara T, Sugimoto H. Microglia-derived interleukin-6 and leukaemia inhibitory factor promote astro­cytic differentiation of neural stem/progenitor cells. Eur J Neurosci. 2007;25(3):649–58.
122. Bogdan C, Paik J, Vodovotz Y, Nathan C. Contrasting mechanisms for sup­pression of macrophage cytokine release by transforming growth-factor-beta and interleukin-10. J Biol Chem. 1992;267(32):23301–8.
123. Cassatella MA, Meda L, Gasperini S, Calzetti F, Bonora S. Interleukin-10 (IL-10) up-regulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying messenger-RNA degradation. J Exp Med. 1994;179(5):1695–9.
124. Knoblach SM, Faden AI. Interleukin-10 improves outcome and alters proin­flammatory cytokine expression after experimental traumatic brain injury. Exp Neurol. 1998;153(1):143–51.
125. Shimonkevitz R, Bar-Or D, Harris L, Dole K, McLaughlin L, Yukl R. Tran­sient monocyte release of interleukin-10 in response to traumatic brain injury. Shock. 1999;12(1):10–6.
126. Hensler T, Sauerland S, Riess P, et al. The effect of additional brain injury on systemic interleukin (IL)-10 and IL-13 levels in trauma patients. Inflamm Res. 2000;49(10):524–8.
127. Csuka E, Morganti-Kossmann MC, Lenzlinger PM, Joller H, Trentz O, Koss­mann T. IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta 1 and blood-brain barrier function. J Neuroimmunol. 1999;101(2):211–21.
128. Finch CE, Laping NJ, Morgan TE, Nichols NR, Pasinetti GM. Tgf-beta-1 is an organizer of responses to neurodegeneration. J Cell Biochem. 1993;53(4):314–22.
129. Acarin L, González B, Castellano B. Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain. Eur J Neurosci. 2000;12(10):3505–20.
130. Zhu Y, Roth-Eichhorn S, Braun N, Culmsee C, Rami A, Krieglstein J. The expression of transforming growth factor-beta1 (TGF-β1) in hippocampal neu­rons: a temporary upregulated protein level after transient forebrain ischemia in the rat. Brain Res. 2000;866(1):286–98.
131. Knuckey NW, Finch P, Palm DE, et al. Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus fol­lowing transient forebrain ischemia. Brain Res Mol Brain Res. 1996;40(1):1–14.
132. Lehrmann E, Kiefer R, Finsen B, Diemer NH, Zimmer J, Hartung HP. Cytok­ines in cerebral ischemia: expression of transforming growth factor beta-1 (TGF-beta 1) mRNA in the postischemic adult rat hippocampus. Exp Neurol. 1995;131(1):114–23.
133. Buckwalter MS, Yamane M, Coleman BS, et al. Chronically increased trans­forming growth factor-β1 strongly inhibits hippocampal neurogenesis in aged mice. Am J Pathol. 2006;169(1):154–64.
134. Wachs FP, Winner B, Couillard-Despres S, et al. Transforming growth factor-beta1 is a negative modulator of adult neurogenesis. J Neuropathol Exp Neurol. 2006;65(4):358–70.
135. Ma M, Ma Y, Yi X, et al. Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone. BMC Neurosci. 2008;9(1):117.
136. Anthony D, Dempster R, Fearn S, et al. CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood-brain barrier breakdown. Curr Biol. 1998;8(16):923–6.
137. Herx LM, Yong VW. Interleukin-1βis required for the early evolution of reactive astrogliosis following CNS lesion. J Neuropathol Exp Neurol. 2001;60(10):961–71.
138. Cui M, Huang Y, Tian C, Zhao Y, Zheng J. FOXO3a inhibits TNF-alpha- and IL-1beta-induced astrocyte proliferation: implication for reactive astrogliosis. Glia. 2011;59(4):641–54.
139. Liberto CM, Albrecht PJ, Herx LM, Yong VW, Levison SW. Pro-regener­ative properties of cytokine-activated astrocytes. J Neurochem. 2004;89(5):1092–100.
140. Basu A, Krady JK, O’Malley M, Styren SD, DeKosky ST, Levison SW. The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. J Neurosci. 2002;22(14):6071–82.
141. Ching S, He L, Lai W, Quan N. IL-1 type I receptor plays a key role in mediat­ing the recruitment of leukocytes into the central nervous system. Brain Behav Immun. 2005;19(2):127–37.
142. Heese K, Hock C, Otten U. Inflammatory signals induce neurotrophin expres­sion in human microglial cells. J Neurochem. 1998;70(2):699–707.
143. Gabay C. Lamacchia C, Palmer G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol. 2010;6:232–41.
144. Kuldo JM. Differential effects of NF-{kappa}B and p38 MAPK inhibi­tors and combinations thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of endothelial cells in vitro. Am J Physiol Cell Physiol. 2005;289(5):C1229–39.
145. Friedman WJ. Interactions of interleukin-1 with neurotrophic factors in the cen­tral nervous system. Mol Neurobiol. 2005;32(2):133–44.
146. da Cunha A, Vitkovic L. Transforming growth factor-beta 1 (TGF-beta 1) expression and regulation in rat cortical astrocytes. J Neuroimmunol. 1992;36(2–3):157–69.
147. Araujo DM, Cotman CW. Basic FGF in astroglial, microglial, and neuronal cul­tures: characterization of binding sites and modulation of release by lymphokines and trophic factors. J Neurosci. 1992;12(5):1668–78.
148. Lapchak PA, Araujo DM, Carswell S, Hefti F. Distribution of [125I]nerve growth factor in the rat brain following a single intraventricular injection: cor­relation with the topographical distribution of trkA messenger RNA-expressing cells. Neuroscience. 1993;54(2):445–60.
149. Tong L, Balazs R, Soiampornkul R, Thangnipon W, Cotman CW. Interleukin-1. Neurobiol Aging. 2008;29(9):1380–93.
150. Tong L, Prieto GA, Kramár EA, et al. Brain-derived neurotrophic factor-depen­dent synaptic plasticity is suppressed by interleukin-1βvia p38 mitogen-activated protein kinase. J Neurosci. 2012;32(49):17714–24.
151. Smith ED, Prieto GA, Tong L, et al. Rapamycin and interleukin-1 impair brain-derived neurotrophic factor-dependent neuron survival by modulating autophagy. J Biol Chem. 2014;289(30):20615–29.
152. Peng H, Erdmann N, Whitney N, et al. HIV-1-infected and/or immune acti­vated macrophages regulate astrocyte SDF-1 production through IL-1β. Glia. 2006;54(6):619–29.
153. Calderon TM, Eugenin EA, Lopez L, et al. A role for CXCL12 (SDF-1α) in the pathogenesis of multiple sclerosis: regulation of CXCL12 expression in astrocytes by soluble myelin basic protein. J Neuroimmunol. 2006;177(1–2):27–39.
154. Dziegielewska KM, Møller JE, Potter AM, Ek J, Lane MA, Saunders NR. Acute-phase cytokines IL-1βand TNF-α in brain development. Cell Tissue Res. 2000;299(3):335–45.
155. Gourin CG, Shackford SR. Production of tumor necrosis factor-alpha and interleukin-1beta by human cerebral microvascular endothelium after percussive trauma. J Trauma Acute Care Surg. 1997;42(6):1101–7.
156. Chao CC, Hu SX, Ehrlich L, Peterson PK. Interleukin-1 and tumor necrosis factor-α synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain Behav Immun. 1995;9(4):355–65.
157. Downen M, Amaral TD, Hua LL, Zhao ML, Lee SC. Neuronal death in cytokine-activated primary human brain cell culture: role of tumor necrosis factor-alpha. Glia. 1999;28(2):114–27.
158. Gadient RA, Cron KC, Otten U. Interleukin-1 βand tumor necrosis factor-α synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes. Neurosci Lett. 1990;117(3):335–40.
159. Yao JS, Zhai W, Young WL, Yang G-Y. Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: the role for KDR and MMP−9. Biochem Biophys Res Commun. 2006;342(4):1396–404.
160. Fee D, Grzybicki D, Dobbs M, et al. Interleukin 6 promotes vasculogenesis of murine brain microvessel endothelial cells. Cytokine. 2000;12(6):655–65.
161. Loganadane LD, Berge N, Legrand C, FauvelLafeve F. Endothelial cell prolif­eration regulated by cytokines modulates thrombospondin-1 secretion into the subendothelium. Cytokine. 1997;9(10):740–6.
162. Giraudo E, Arese M, Toniatti C, et al. IL-6 is an in vitro and in vivo autocrine growth factor for middle T antigen-transformed endothelial cells. J Immunol. 1996;157(6):2618–23.
163. Kremlev SG, Palmer C. Interleukin-10 inhibits endotoxin-induced pro-inflammatory cytokines in microglial cell cultures. J Neuroimmunol. 2005;162(1–2):71–80.
164. Sawada M, Suzumura A, Hosoya H, Marunouchi T, Nagatsu T. Interleu­kin-10 inhibits both production of cytokines and expression of cytokine receptors in microglia. J Neurochem. 1999;72(4):1466–71.
165. Benveniste EN, Tang LP, Law RM. Differential regulation of astrocyte TNF-α expression by the cytokines TGF-β, IL-6 and IL-10. Int J Dev Neurosci. 1995;13(3):341–9.
166. Freire-de-Lima CG, Xiao YQ, Gardai SJ, Bratton DL, Schiemann WP, Henson PM. Apoptotic cells, through transforming growth factor-β, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages. J Biol Chem. 2006;281(50):38376–84.
167. Yu P, Wang H, Katagiri U, Geller HM. An in vitro model of reactive astrogliosis and its effect on neuronal growth. Methods Mol Biol. 2012;814:327–40.
168. Yu Z, Yu P, Chen H, Geller HM. Targeted inhibition of KCa3.1 attenuates TGF-β-induced reactive astrogliosis through the Smad2/3 signaling pathway. J Neurochem. 2014;130(1):41–9.
169. Mahmood A, Lu D, Lu M, Chopp M. Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells. Neurosurgery. 2003;53(3):697–703.
170. Mahmood A, Lu D, Wang L, Li Y, Lu M, Chopp M. Treatment of traumatic brain injury in female rats with intravenous administration of bone marrow stromal cells. Neurosurgery. 2001;49(5):1196–203.
171. Qu C, Mahmood A, Lu D, Goussev A, Xiong Y, Chopp M. Treatment of trau­matic brain injury in mice with marrow stromal cells. Brain Res. 2008;1208:234–9.
172. Grigoriadis N, Lourbopoulos A, Lagoudaki R, et al. Experimental neurology. Exp Neurol. 2011;230(1):78–89.
173. Snyder EY. Experimental neurology. Exp Neurol. 2011;230(1):75–7.
174. Shear DA, Tate MC, Archer DR, et al. Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury. Brain Res. 2004;1026(1):11–22.
175. Bush TG, Puvanachandra N, Horner CH, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron. 1999;23(2):297–308.
176. Shear DA, Tate CC, Tate MC, et al. Stem cell survival and functional outcome after traumatic brain injury is dependent on transplant timing and location. Restor Neurol Neurosci. 2011;29(4):215–25.
177. Riess P, Zhang C, Saatman KE, et al. Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental trau­matic brain injury. Neurosurgery. 2002;51(4):1043–54.
178. Wennersten A, Meijer X, Holmin S, Wahlberg L, Mathiesen T. Prolif­eration, migration, and differentiation of human neural stem/progenitor cells after transplantation into a rat model of traumatic brain injury. J Neurosurg. 2004;100(1):88–96.
179. Harting MT, Sloan LA, Jimenez F, Baumgartner J, Cox CS. Subacute neural stem cell therapy for traumatic brain injury. J Surg Res. 2009;153(2):188–94.
180. Kamei N, Tanaka N, Oishi Y, et al. BDNF, NT-3, and NGF released from trans­planted neural progenitor cells promote corticospinal axon growth in organo­typic cocultures. Spine. 2007;32(12):1272–8.
181. Kim H-J, Lee J-H, Kim S-H. Therapeutic effects of human mesenchymal stem cells on traumatic brain injury in rats: secretion of neurotrophic factors and inhi­bition of apoptosis. J Neurotrauma. 2010;27(1):131–8.
182. Chen X, Katakowski M, Li Y, et al. Human bone marrow stromal cell cul­tures conditioned by traumatic brain tissue extracts: growth factor production. J Neurosci Res. 2002;69(5):687–91.
183. Ma H, Yu B, Kong L, Zhang Y, Shi Y. Neural stem cells over-expressing brain-derived neurotrophic factor (BDNF) stimulate synaptic protein expression and promote functional recovery following transplantation in rat model of traumatic brain injury. Neurochem Res. 2012;37(1):69–83.
184. Wang Z, Yao W, Deng Q, Zhang X, Zhang J. Protective effects of BDNF over­expression bone marrow stromal cell transplantation in rat models of traumatic brain injury. J Mol Neurosci. 2012;49(2):409–16.
185. Wang Z, Wang Y, Wang Z, et al. Engineered mesenchymal stem cells with enhanced tropism and paracrine secretion of cytokines and growth factors to treat traumatic brain injury. Stem Cells. 2014;33(2):456–67.
186. Bang OY, Jin KS, Hwang MN, et al. The effect of CXCR4 overexpres­sion on mesenchymal stem cell transplantation in ischemic stroke. Cell Med. 2012;4(2):65–76.
187. Gao J, Prough DS, McAdoo DJ, et al. Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury. Exp Neurol. 2006;201(2):281–92.
188. Park KI, Teng YD, Snyder EY. The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat Biotech. 2002;20(11):1111–7.
189. Heffernan JM, Overstreet DJ, Le LD, Vernon BL, Sirianni RW. Bioengineered scaffolds for 3D analysis of glioblastoma proliferation and invasion. Ann Biomed Eng. 2014. [Epub ahead of print].
190. Lu YB, Franze K, Seifert G, et al. Viscoelastic properties of individual glial cells and neurons in the CNS. Proc Natl Acad Sci U S A. 2006;103(47):17759–64.
191. Qu C, Mahmood A, Liu XS, et al. The treatment of TBI with human marrow stromal cells impregnated into collagen scaffold: functional outcome and gene expression profile. Brain Res. 2011;1371:129–39.
192. Xiong Y, Qu C, Mahmood A, et al. Delayed transplantation of human mar­row stromal cell-seeded scaffolds increases transcallosal neural fiber length, angiogenesis, and hippocampal neuronal survival and improves func­tional outcome after traumatic brain injuryin rats. Brain Res. 2009;1263:183–91.
193. Lu D, Mahmood A, Qu C, Hong X, Kaplan D, Chopp M. Collagen scaf­folds populated with human marrow stromal cells reduce lesion volume and improve functional outcome after traumatic brain injury. Neurosurgery. 2007;61(3):596.
194. Mahmood A, Wu H, Qu C, et al. Suppression of neurocan and enhancement of axonal density in rats after treatment of traumatic brain injury with scaffolds impregnated with bone marrow stromal cells: laboratory investigation. J Neuro­surg. 2015;120(5):1147–55.
195. Guan J, Zhu Z, Zhao RC, et al. Transplantation of human mesenchymal stem cells loaded on colalgen scaffolds for the treatment of traumatic brain injury in rats. Biomaterials. 2013;34(24):5937–46.
196. Cheng T-Y, Chen M-H, Chang W-H, Huang M-Y, Wang T-W. Biomaterials. Biomaterials. 2013;34(8):2005–16.
197. Tate CC, Shear DA, Tate MC, Archer DR, Stein DG, LaPlaca MC. Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. J Tissue Eng Regen Med. 2009;3(3):208–17.
198. Delcroix GJ, Schiller PC, Benoit J-P, Montero-Menei CN. Biomaterials. Biomaterials. 2010;31(8):2105–20.
199. Yi X, Manickam DS, Brynskikh A, Kabanov AV. Agile delivery of protein thera­peutics to CNS. J Control Release. 2014;190:637–63.
200. Pencea V, Bingaman KD, Wiegand SJ, Luskin MB. Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neu­rons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci. 2001;21(17):6706–17.
201. Bicker J, Alves G, Fortuna A, Falcão A. Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review. Eur J Pharm Biopharm. 2014;87(3):409–32.
202. Patel T, Zhou J, Piepmeier JM, Saltzman WM. Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev. 2012;64(7):701–5.
203. Li ZW, Tang RH, Zhang JP, et al. Inhibiting epidermal growth factor receptor attenuates reactive astrogliosis and improves functional outcome after spinal cord injury in rats. Neurochem Int. 2011;58(7):812–9.
204. Lau TT, Wang D-A. Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine. Expert Opin Biol Ther. 2011;11(2):189–97.
205. Sun W, Liu J, Huan Y, Zhang C. Intracranial injection of recombinant strom­al-derived factor-1 alpha (SDF-1α) attenuates traumatic brain injury in rats. Inflamm Res. 2014;63(4):287–97.
206. Henderson PW, Singh SP, Krijgh DD, et al. Stromal-derived factor-1 delivered via hydrogel drug-delivery vehicle accelerates wound healing in vivo. Wound Repair Regen. 2011;19(3):420–5.
207. Rabbany SY, Pastore J, Yamamoto M, et al. Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing. Cell Trans­plant. 2010;19(4):399–408.
208. Fujio M, Yamamoto A, Ando Y, et al. Stromal cell-derived factor-1 enhances distraction osteogenesis-mediated skeletal tissue regeneration through the recruitment of endothelial precursors. Bone. 2011;49(4):693–700.
209. Higashino K, Viggeswarapu M, Bargouti M, Liu H, Titus L, Boden SD. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation. Tissue Eng Part A. 2011;17(3–4):523–30.
210. Segers VF, Tokunou T, Higgins LJ, MacGillivray C, Gannon J, Lee RT. Local delivery of protease-resistant stromal cell derived factor-1 for stem cell recruit­ment after myocardial infarction. Circulation. 2007;116(15):1683–92.
211. Prokoph S, Chavakis E, Levental KR, et al. Sustained delivery of SDF-1alpha from heparin-based hydrogels to attract circulating pro-angiogenic cells. Bioma­terials. 2012;33(19):4792–800.
212. Baumann L, Prokoph S, Gabriel C, Freudenberg U, Werner C, Beck-Sickinger AG. A novel, biased-like SDF-1 derivative acts synergistically with starPEG-based heparin hydrogels and improves eEPC migration in vitro. J Control Release. 2012;162(1):68–75.
213. Cross DP, Wang C. Stromal-derived factor-1 alpha-loaded PLGA microspheres for stem cell recruitment. Pharm Res. 2011;28(10):2477–89.
214. Huang Y-C, Liu T-J. Mobilization of mesenchymal stem cells by stromal cell-derived factor-1 released from chitosan/tripolyphosphate/fucoidan nanopar­ticles. Acta Biomater. 2012;8(3):1048–56.
215. He X, Ma J, Jabbari E. Migration of marrow stromal cells in response to sus­tained release of stromal-derived factor-1α from poly(lactide ethylene oxide fumarate) hydrogels. Int J Pharm. 2010;390(2):107–16.
216. Thau-Zuchman O, Shohami E, Alexandrovich AG, Leker RR. Combina­tion of vascular endothelial and fibroblast growth factor 2 for induction of neurogenesis and angiogenesis after traumatic brain injury. J Mol Neurosci. 2012;47(1):166–72.
217. Thau-Zuchman O, Shohami E, Alexandrovich AG, Leker RR. Vascular endothelial growth factor increases neurogenesis after traumatic brain injury. J Cereb Blood Flow Metab. 2010;30(5):1008–16.
218. Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003;111(12):1843–51.
219. Lee C, Agoston DV. Vascular endothelial growth factor is involved in mediat­ing increased de novo hippocampal neurogenesis in response to traumatic brain injury. J Neurotrauma. 2010;27(3):541–53.
220. Yang JP, Liu HJ, Cheng SM, et al. Direct transport of VEGF from the nasal cavity to brain. Neurosci Lett. 2009;449(2):108–11.
221. Yang JP, Liu HJ, Wang ZL, et al. The dose-effectiveness of intranasal VEGF in treatment of experimental stroke. Neurosci Lett. 2009;461(3):212–6.
222. Emerich DF, Mooney DJ, Storrie H, Babu RS, Kordower JH. Injectable hydrogels providing sustained delivery of vascular endothelial growth factor are neuropro­tective in a rat model of Huntington’s disease. Neurotox Res. 2010;17(1):66–74.
223. Shen F, Fan Y, Su H, et al. Adeno-associated viral vector-mediated hypoxia-regulated VEGF gene transfer promotes angiogenesis following focal cerebral ischemia in mice. Gene Ther. 2008;15(1):30–9.
224. Tian YY, Tang CJ, Wang JN, et al. Favorable effects of VEGF gene transfer on a rat model of Parkinson disease using adeno-associated viral vectors. Neurosci Lett. 2007;421(3):239–44.
225. Kuhn HG, Winkler J, Kempermann G, Thal LJ, Gage FH. Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci. 1997;17(15):5820–9.
226. Wagner JP, Black IB, DiCicco Bloom E. Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor. J Neurosci. 1999;19(14):6006–16.
227. Hayamizu TF, Chan PT, Johanson CE. FGF-2 immunoreactivity in adult rat ependyma and choroid plexus: responses to global forebrain ischemia and intra­ventricular FGF−2. Neurol Res. 2001;23(4):353–8.
228. Wu D, Song B-W, Vinters HV, Pardridge WM. Pharmacokinetics and brain uptake of biotinylated basic fibroblast growth factor conjugated to a blood-brain barrier drug delivery system. J Drug Target. 2002;10(3):239–45.
229. Song B-W, Vinters HV, Wu D, Pardridge WM. Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjuga­tion to a blood-brain barrier delivery vector. J Pharmacol Exp Ther. 2002;301(2):605–10.
230. Sun D, Bullock MR, McGinn MJ, et al. Experimental neurology. Exp Neurol. 2009;216(1):56–65.
231. Yan HQ, Yu J, Kline AE, et al. Evaluation of combined fibroblast growth factor-2 and moderate hypothermia therapy in traumatically brain injured rats. Brain Res. 2000;887(1):134–43.
232. Dietrich WD, Alonso O, Busto R, Finklestein SP. Posttreatment with intrave­nous basic fibroblast growth factor reduces histopathological damage following fluid-percussion brain injury in rats. J Neurotrauma. 1996;13(6):309–16.
233. Mudò G, Bonomo A, Liberto VD, Frinchi M, Fuxe K, Belluardo N. The FGF-2/FGFRs neurotrophic system promotes neurogenesis in the adult brain. J Neural Transm. 2009;116(8):995–1005.
234. Galderisi U, Peluso G, Di Bernardo G, et al. Efficient cultivation of neural stem cells with controlled delivery of FGF-2. Stem Cell Res. 2013;10(1):85–94.
235. Skop NB, Calderon F, Levison SW, Gandhi CD, Cho CH. Heparin crosslinked chitosan microspheres for the delivery of neural stem cells and growth factors for central nervous system repair. Acta Biomater. 2013;9(6):6834–43.
236. Jeon O, Kang S-W, Lim H-W, Hyung Chung J, Kim B-S. Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel. Biomaterials. 2006;27(8):1598–607.
237. Jimenez Hamann MC, Tator CH, Shoichet MS. Injectable intrathecal delivery system for localized administration of EGF and FGF-2 to the injured rat spinal cord. Exp Neurol. 2005;194(1):106–19.
238. Leker RR, Soldner F, Velasco I, Gavin DK, Androutsellis-Theotokis A, McKay RD. Long-lasting regeneration after ischemia in the cerebral cortex. Stroke. 2007;38(1):153–61.
239. Sun D, Bullock MR, Altememi N, et al. The effect of epidermal growth factor in the injured brain after trauma in rats. J Neurotrauma. 2010;27(5):923–38.
240. Kopec AM, Carew TJ. Growth factor signaling and memory formation: temporal and spatial integration of a molecular network. Learn Mem. 2013;20(10):531–9.
241. Kornblum HI, Zurcher SD, Werb Z, Derynck R, Seroogy KB. Multiple trophic actions of heparin-binding epidermal growth factor (HB-EGF) in the central nervous system. Eur J Neurosci. 1999;11(9):3236–46.
242. Cooke MJ, Wang Y, Morshead CM, Shoichet MS. Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain. Biomaterials. 2011;32(24):5688–97.
243. Sugiura S, Kitagawa K, Tanaka S, et al. Adenovirus-mediated gene transfer of hep­arin-binding epidermal growth factor-like growth factor enhances neurogenesis and angiogenesis after focal cerebral ischemia in rats. Stroke. 2005;36(4):859–64.
244. Berry M, Ahmed Z, Douglas MR, Logan A. Epidermal growth factor receptor antagonists and CNS axon regeneration: mechanisms and controversies. Brain Res Bull. 2011;84(4–5):289–99.
245. Rabchevsky AG, Weinitz JM, Coulpier M, Fages C, Tinel M, Junier MP. A role for transforming growth factor alpha as an inducer of astrogliosis. J Neurosci. 1998;18(24):10541–52.
246. Wu H, Mahmood A, Lu D, et al. Attenuation of astrogliosis and modulation of endothelial growth factor receptor in lipid rafts by simvastatin after traumatic brain injury. J Neurosurg. 2010;113(3):591–7.
247. Li ZW, Li JJ, Wang L, et al. Epidermal growth factor receptor inhibitor amelio­rates excessive astrogliosis and improves the regeneration microenvironment and functional recovery in adult rats following spinal cord injury. J Neuroinflamma­tion. 2014;11(1):71.
248. Robinson R, Viviano SR, Criscione JM, et al. Nanospheres delivering the EGFR TKI AG1478 promote optic nerve regeneration: the role of size for intraocular drug delivery. ACS Nano. 2011;5(6):4392–400.
249. Zheng J, Shen WH, Lu TJ, et al. Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated neuronal protection and dendritic growth. J Biol Chem. 2008;283(19):13280–8.
250. Weinstein DE, Burrola P, Kilpatrick TJ. Increased proliferation of precursor cells in the adult rat brain after targeted lesioning. Brain Res. 1996;743(1–2):11–6.
251. Huang F, Yin Z, Wu D, Hao J. Effects of controlled release of brain-derived neurotrophic factor from collagen gel on rat neural stem cells. Neuroreport. 2013;24(3):101–7.
252. Fon D, Zhou K, Ercole F, et al. Nanofibrous scaffolds releasing a small molecule BDNF-mimetic for the re-direction of endogenous neuroblast migration in the brain. Biomaterials. 2014;35(9):2692–712.
253. Horne MK, Nisbet DR, Forsythe JS, Parish CL. Three-dimensional nanofibrous scaffolds incorporating immobilized BDNF promote proliferation and differen­tiation of cortical neural stem cells. Stem Cells Dev. 2010;19(6):843–52.
254. Alcalá-Barraza SR, Lee MS, Hanson LR, McDonald AA, Frey WH, McLoon LK. Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS. J Drug Target. 2010;18(3):179–90.
255. Bertram JP, Rauch MF, Chang K, Lavik EB. Using polymer chemistry to modu­late the delivery of neurotrophic factors from degradable microspheres: delivery of BDNF. Pharm Res. 2010;27(1):82–91.
256. Uchida K, Nakajima H, Hirai T, et al. The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice. Spine. 2012;37(26):2125–35.
257. Martens DJ, Seaberg RM, van der Kooy D. In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord. Eur J Neurosci. 2002;16(6):1045–57.
258. Nakaguchi K, Jinnou H, Kaneko N, et al. Growth factors released from gelatin hydrogel microspheres increase new neurons in the adult mouse brain. Stem Cells Int. 2012;2012:e915160.
259. Wang Y, Cooke MJ, Sachewsky N, Morshead CM, Shoichet MS. Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke. J Control Release. 2013;172(1):1–11.
260. Wang Y, Wei YT, Zu ZH, et al. Combination of hyaluronic acid hydrogel scaf­fold and PLGA microspheres for supporting survival of neural stem cells. Pharm Res. 2011;28(6):1406–14.
261. Lee K, Silva EA, Mooney DJ. Growth factor delivery-based tissue engineer­ing: general approaches and a review of recent developments. J R Soc Interface. 2011;8(55):153–70.
262. Overstreet DJ, Dutta D, Stabenfeldt SE, Vernon BL. Injectable hydrogels. J Polym Sci B Polym Phys. 2012;50(13):881–903.
263. Löscher W, Potschka H. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog Neurobiol. 2005;76(1):22–76.
264. Morganti-Kossmann MC, Satgunaseelan L, Bye N, Kossmann T. Modulation of immune response by head injury. Injury. 2007;38(12):1392–400.
265. Kossmann T, Hans VH, Imhof HG, et al. Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock. 1995;4(5):311–7.
266. Romano M, Sironi M, Toniatti C, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997;6(3):315–25.
267. Jaerve A, Schira J, Müller HW. Concise review: the potential of stromal cell-derived factor 1 and its receptors to promote stem cell functions in spinal cord repair. Stem Cells Transl Med. 2012;1(10):732–9.