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Extrinsic cellular and molecular mediators of peripheral axonal regeneration

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Abstract

The ability of injured peripheral nerves to regenerate and reinnervate their original targets is a characteristic feature of the peripheral nervous system (PNS). On the other hand, neurons of the central nervous system (CNS), including retinal ganglion cell (RGC) axons, are incapable of spontaneous regeneration. In the adult PNS, axonal regeneration after injury depends on well-orchestrated cellular and molecular processes that comprise a highly reproducible series of degenerative reactions distal to the site of injury. During this fine-tuned process, named Wallerian degeneration, a remodeling of the distal nerve fragment prepares a permissive microenvironment that permits successful axonal regrowth originating from the proximal nerve fragment. Therefore, a multitude of adjusted intrinsic and extrinsic factors are important for surviving neurons, Schwann cells, macrophages and fibroblasts as well as endothelial cells in order to achieve successful regeneration. The aim of this review is to summarize relevant extrinsic cellular and molecular determinants of successful axonal regeneration in rodents that contribute to the regenerative microenvironment of the PNS.

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References

  • Barrette B, Hebert MA, Filali M, Lafortune K, Vallieres N, Gowing G, Julien JP, Lacroix S (2008) Requirement of myeloid cells for axon regeneration. J Neurosci 28:9363–9376

    PubMed  CAS  Google Scholar 

  • Be’eri H, Reichert F, Saada A, Rotshenker S (1998) The cytokine network of wallerian degeneration: IL-10 and GM-CSF. Eur J Neurosci 10:2707–2713

    Google Scholar 

  • Boivin A, Pineau I, Barrette B, Filali M, Vallieres N, Rivest S, Lacroix S (2007) Toll-like receptor signaling is critical for Wallerian degeneration and functional recovery after peripheral nerve injury. J Neurosci 27:12565–12576

    PubMed  CAS  Google Scholar 

  • Bosse F, Zoidl G, Wilms S, Gillen CP, Kuhn HG, Müller HW (1994) Differential expression of two mRNA species indicates a dual function of peripheral myelin protein PMP22 in cell growth and myelination. J Neurosci Res 37:529–537

    PubMed  CAS  Google Scholar 

  • Bosse F, Hasenpusch-Theil K, Küry P, Müller HW (2006) Gene expression profiling reveals that peripheral nerve regeneration is a consequence of both novel injury-dependent and reactivated developmental processes. J Neurochem 96:1441–1457

    PubMed  CAS  Google Scholar 

  • Bouldin TW, Earnhardt TS, Goines ND (1991) Restoration of blood-nerve barrier in neuropathy is associated with axonal regeneration and remyelination. J Neuropathol Exp Neurol 50:719–728

    PubMed  CAS  Google Scholar 

  • Brown MC, Lunn ER, Perry VH (1992) Consequences of slow Wallerian degeneration for regenerating motor and sensory axons. J Neurobiol 23:521–536

    PubMed  CAS  Google Scholar 

  • Brück W, Friede RL (1991) The role of complement in myelin phagocytosis during PNS Wallerian degeneration. J Neurol Sci 103:182–187

    PubMed  Google Scholar 

  • Camara-Lemarroy CR, Guzman-de la Garza FJ, Fernandez-Garza NE (2010) Molecular inflammatory mediators in peripheral nerve degeneration and regeneration. Neuroimmunomodulation 17:314–324

    PubMed  CAS  Google Scholar 

  • Cao ZX, Gao Y, Bryson JB, Hou JW, Chaudhry N, Siddiq M, Martinez J, Spencer T, Carmel J, Hart RB, Filbin MT (2006) The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth. J Neurosci 26:5565–5573

    PubMed  CAS  Google Scholar 

  • Carroll SL, Frohnert PW (1998) Expression of JE (Monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL/Wld(s) mice. J Neuropathol Exp Neurol 57:915–930

    PubMed  CAS  Google Scholar 

  • Chan JR, Cosgaya JM, Wu YJ, Shooter EM (2001) Neurotrophins are key mediators of the myelination program in the peripheral nervous system. Proc Natl Acad Sci USA 98:14661–14668

    PubMed  CAS  Google Scholar 

  • Chattopadhyay S, Myers RR, Janes J, Shubayev V (2007) Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve. Brain Behav Immun 21:561–568

    PubMed  CAS  Google Scholar 

  • Chen ZL, Strickland S (2003) Laminin gamma 1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve. J Cell Biol 163:889–899

    PubMed  CAS  Google Scholar 

  • Chen YY, McDonald D, Cheng C, Magnowski B, Durand J, Zochodne DW (2005) Axon and Schwann cell partnership during nerve regrowth. J Neuropathol Exp Neurol 64:613–622

    PubMed  Google Scholar 

  • Chen ZL, Yu WM, Strickland S (2007) Peripheral regeneration. Annu Rev Neurosci 30:209–233

    PubMed  Google Scholar 

  • Chui R, Dorovini-Zis K (2010) Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide. J Neuroinflammation 7:1–12

    PubMed  Google Scholar 

  • Coleman M (2005) Axon degeneration mechanisms: Commonality amid diversity. Nature Rev Neurosci 6:889–898

    CAS  Google Scholar 

  • Coleman MP, Freeman MR (2010) Wallerian Degeneration, Wld(S), and Nmnat. Annu Rev Neurosci 33:245–267

    PubMed  CAS  Google Scholar 

  • Condic ML (2001) Adult neuronal regeneration induced by transgenic integrin expression. J Neurosci 21:4782–4788

    PubMed  CAS  Google Scholar 

  • Cosgaya JM, Chan JR, Shooter EM (2002) The neurotrophin receptor p75(NTR) as a positive modulator of myelination. Science 298:1245–1248

    PubMed  CAS  Google Scholar 

  • Cullen MJ (1988) Freeze-fracture analysis of myelin membrane changes in Wallerian degeneration. J Neurocytol 17:105–115

    PubMed  CAS  Google Scholar 

  • Dailey AT, Avellino AM, Benthem L, Silver J, Kliot M (1998) Complement depletion reduces macrophage infiltration and activation during Wallerian degeneration and axonal regeneration. J Neurosci 18:6713–6722

    PubMed  CAS  Google Scholar 

  • David S, Fry EJ, Lopez-Vales R (2008) Novel roles for Nogo receptor in inflammation and disease. Trends Neurosci 31:221–226

    PubMed  CAS  Google Scholar 

  • De S, Trigueros MA, Kalyvas A, David S (2003) Phospholipase A2 plays an important role in myelin breakdown and phagocytosis during Wallerian degeneration. Mol Cell Neurosci 24:753–765

    PubMed  CAS  Google Scholar 

  • Doyu M, Sobue G, Ken E, Kimata K, Shinomura T, Yamada Y, Mitsuma T, Takahashi A (1993) Laminin-A, laminin-B1, and laminin-B2 chain gene-expression in transected and regenerating nerves - regulation by axonal signals. J Neurochem 60:543–551

    PubMed  CAS  Google Scholar 

  • Eggers R, Tannemaat MR, Ehlert EM, Verhaagen J (2010) A spatio-temporal analysis of motorneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral rootavulsion and implantation. Exp Neurol 223:207–220

    PubMed  CAS  Google Scholar 

  • Fenrich K, Gordon T (2004) Canadian Association of Neuroscience review: Axonal regeneration in the peripheral and central nervous systems - Current issues and advances. Can J Neurol Sci 31:142–156

    PubMed  Google Scholar 

  • Fry EJ, Ho C, David S (2007) A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron 53:649–662

    PubMed  CAS  Google Scholar 

  • Fukaya K, Hasegawa M, Mashitani T, Kadoya T, Horie H, Hayashi Y, Fujisawa H, Tachibana O, Kida S, Yamashita J (2003) Oxidized galectin-1 stimulates the migration of Schwann cells from both proximal and distal stumps of transected nerves and promotes axonal regeneration after peripheral nerve injury. J Neuropathol Exp Neurol 62:162–172

    PubMed  CAS  Google Scholar 

  • Gantus MAV, Nasciutti LE, Cruz CM, Persechini PM, Martinez AMB (2006) Modulation of extracellular matrix components by metalloproteinases and their tissue inhibitors during degeneration and regeneration of rat sural nerve. Brain Res 1122:36–46

    PubMed  CAS  Google Scholar 

  • Gardiner NJ (2011) Integrins and the extracellular matrix: key mediators of development and regeneration of the sensory nervous system. Dev Neurobiol 71:1054–1072

    PubMed  CAS  Google Scholar 

  • Gardiner NJ, Fernyhough P, Tomlinson DR, Mayer U, der Mark H, Streuli CH (2005) alpha 7 integrin mediates neurite outgrowth of distinct populations of adult sensory neurons. Mol Cell Neurosci 28:229–240

    PubMed  CAS  Google Scholar 

  • Gardiner NJ, Moffatt S, Fernyhough P, Humphries MJ, Streuli CH, Tomlinson DR (2007) Preconditioning injury-induced neurite outgrowth of adult rat sensory neurons on fibronectin is mediated by mobilisation of axonal alpha5 integrin. Mol Cell Neurosci 35:249–260

    PubMed  CAS  Google Scholar 

  • Gaudet AD, Leung M, Poirier F, Kadoya T, Horie H, Ramer MS (2009) A role for galectin-1 in the immune response to peripheral nerve injury. Exp Neurol 220:320–327

    PubMed  CAS  Google Scholar 

  • Gillingwater TH, Ribchester RR (2001) Compartmental neurodegeneration and synaptic plasticity in the Wld(s) mutant mouse. J Physiol 534:627–639

    Google Scholar 

  • Goethals S, Ydens E, Timmerman V, Janssens S (2010) Toll-like receptor expression in the peripheral nerve. Glia 58:1701–1709

    PubMed  Google Scholar 

  • Gölz G, Uhlmann L, Ludecke D, Markgraf N, Nitsch R, Hendrix S (2006) The cytokine/neurotrophin axis in peripheral axon outgrowth. Eur J Neurosci 24:2721–2730

    PubMed  Google Scholar 

  • Gordon T (2009) The role of neurotrophic factors in nerve regeneration. Neurosurg Focus 26(E3):1–10

    Google Scholar 

  • Gray M, Palispis W, Popovich PG, van Rooijen N, Gupta R (2007) Macrophage depletion alters the blood-nerve barrier without affecting Schwann cell function after neural injury. J Neurosci Res 85:766–777

    PubMed  CAS  Google Scholar 

  • Griffin JW, Thompson WJ (2008) Biology and pathology of nonmyelinating Schwann cells. Glia 56:1518–1531

    PubMed  Google Scholar 

  • Guan W, Puthenveedu MA, Condic ML (2003) Sensory neuron subtypes have unique substratum preference and receptor expression before target innervation. J Neurosci 23:1781–1791

    PubMed  CAS  Google Scholar 

  • Guertin AD, Zhang DP, Mak KS, Alberta JA, Kim HA (2005) Microanatomy of axon/glial signaling during Wallerian degeneration. J Neurosci 25:3478–3487

    PubMed  CAS  Google Scholar 

  • Gupta SK, Poduslo JF, Dunn R, Roder J, Mezei C (1990) Myelin-associated glycoprotein gene expression in the presence and absence of Schwann cell-axonal contact. Dev Neurosci 12:22–33

    PubMed  CAS  Google Scholar 

  • Gustavsson P, Linsmeier CE, Leffler H, Kanje M (2007) Galectin-3 inhibits Schwann cell proliferation in cultured sciatic nerve. Neuroreport 18:669–673

    PubMed  CAS  Google Scholar 

  • Hall SM, Gregson NA (1971) The in vivo and ultrastructural effects of injection of lysophosphatidyl choline into myelinated peripheral nerve fibres of the adult mouse. J Cell Sci 9:769–789

    PubMed  CAS  Google Scholar 

  • Hirota H, Kiyama H, Kishimoto T, Taga T (1996) Accelerated nerve regeneration in mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma. J Exp Med 183:2627–2634

    PubMed  CAS  Google Scholar 

  • Höke A, Redett R, Hameed H, Jari R, Zhou C, Li ZB, Griffin JW, Brushart TM (2006) Schwann cells express motor and sensory phenotypes that regulate axon regeneration. J Neurosci 26:9646–9655

    PubMed  Google Scholar 

  • Horie H, Kadoya T (2000) Identification of oxidized galectin-1 as an initial repair regulatory factor after axotomy in peripheral nerves. Neurosci Res 38:131–137

    PubMed  CAS  Google Scholar 

  • Horie H, Inagaki Y, Sohma Y, Nozawa R, Okawa K, Hasegawa M, Muramatsu N, Kawano H, Horie M, Koyama H, Sakai I, Takeshita K, Kowada Y, Takano M, Kadoya T (1999) Galectin-1 regulates initial axonal growth in peripheral nerves after axotomy. J Neurosci 19:9964–9974

    PubMed  CAS  Google Scholar 

  • Horie H, Kadoya T, Hikawa N, Sango K, Inoue H, Takeshita K, Asawa R, Hiroi T, Sato M, Yoshioka T, Ishikawa Y (2004) Oxidized galectin-1 stimulates macrophages to promote axonal regeneration in peripheral nerves after axotomy. J Neurosci 24:1873–1880

    PubMed  CAS  Google Scholar 

  • Huang JK, Phillips GR, Roth AD, Pedraza L, Shan WS, Belkaid W, Mi S, Fex-Svenningsen A, Florens L, Yates JR, Colman DR (2005) Glial membranes at the node of Ranvier prevent neurite outgrowth. Science 310:1813–1817

    PubMed  CAS  Google Scholar 

  • Hynes RO (2002) Integrins: Bidirectional, allosteric signaling machines. Cell 110:673–687

    PubMed  CAS  Google Scholar 

  • Inagaki Y, Sohma Y, Horie H, Nozawa R, Kadoya T (2000) Oxidized galectin-1 promotes axonal regeneration in peripheral nerves but does not possess lectin properties. Eur J Biochem 267:2955–2964

    PubMed  CAS  Google Scholar 

  • Jesuraj NJ, Nguyen PK, Wood MD, Moore AM, Borschel GH, Mackinnon SE, Sakiyama-Elbert SE (2012) Differential gene expression in motor and sensory Schwann cells in the rat femoral nerve. J Neurosci Res 90:96–104

    PubMed  CAS  Google Scholar 

  • Jin L, Jianghai C, Juan L, Hao K (2009) Pleiotrophin and peripheral nerve injury. Neurosurg Rev 32:387–393

    PubMed  Google Scholar 

  • Kwon YK, Bhattacharyya A, Alberta JA, Giannobile WV, Cheon K, Stiles CD, Pomeroy SL (1997) Activation of ErbB2 during wallerian degeneration of sciatic nerve. J Neurosci 17:8293–8299

    PubMed  CAS  Google Scholar 

  • LeBlanc AC, Poduslo JF (1990) Axonal modulation of myelin gene expression in the peripheral nerve. J Neurosci Res 26:317–326

    PubMed  CAS  Google Scholar 

  • Leclere PG, Norman E, Groutsi F, Coffin R, Mayer U, Pizzey J, Tonge D (2007) Impaired axonal regeneration by isolectin B4-binding dorsal root ganglion neurons in vitro. J Neurosci 27:1190–1199

    PubMed  CAS  Google Scholar 

  • Lee HK, Shin YK, Jung J, Seo SY, Baek SY, Park HT (2009) Proteasome inhibition suppresses Schwann cell dedifferentiation in vitro and in vivo. Glia 57:1825–1834

    PubMed  Google Scholar 

  • Lefcort F, Venstrom K, Mcdonald JA, Reichardt LF (1992) Regulation of expression of fibronectin and its receptor, alpha-5-beta-1, during development and regeneration of peripheral-nerve. Development 116:767–782

    PubMed  CAS  Google Scholar 

  • Lemons ML, Condic ML (2008) Integrin signaling is integral to regeneration. Exp Neurol 209:343–352

    PubMed  CAS  Google Scholar 

  • Lemons ML, Barua S, Abanto ML, Halfter W, Condic ML (2005) Adaptation of sensory neurons to hyalectin and decorin proteoglycans. J Neurosci 25:4964–4973

    PubMed  CAS  Google Scholar 

  • Li XQ, Verge VM, Johnston JM, Zochodne DW (2004) CGRP peptide and regenerating sensory axons. J Neuropathol Exp Neurol 63:1092–1103

    PubMed  CAS  Google Scholar 

  • Lindholm D, Heumann R, Thoenen H (1987) Products of macrophages stimulate nerve growth-factor messenger-RNA synthesis in the injured peripheral-nerve. J Neuroimmunol 16:107

    Google Scholar 

  • Liu L, Lioudyno M, Tao R, Eriksson P, Svensson M, Aldskogius H (1999) Hereditary absence of complement C5 in adult mice influences wallerian degeneration, but not retrograde responses, following injury to peripheral nerve. J Peripher Nerv Syst 4:123–133

    PubMed  CAS  Google Scholar 

  • Liu WQ, Martinez JA, Durand J, Wildering W, Zochodne DW (2009) RGD-mediated adhesive interactions are important for peripheral axon outgrowth in vivo. Neurobiol Dis 34:11–22

    PubMed  CAS  Google Scholar 

  • Lubinska L (1977) Early course of Wallerian degeneration in myelinated fibers of rat phrenic-nerve. Brain Res 130:47–63

    PubMed  CAS  Google Scholar 

  • Lunn ER, Perry VH, Brown MC, Rosen H, Gordon S (1989) v. Eur J Neurosci 1:27–33

    PubMed  CAS  Google Scholar 

  • MacGillavry HD, Cornelis J, van der Kallen LR, Sassen MM, Verhaagen J, Smit AB, van Kesteren RE (2011) Genome-wide gene expression and promoter binding analysis identifies NFIL3 as a repressor of C/EBP target genes in neuronal outgrowth. Mol Cell Neurosci 46:460–468

    PubMed  CAS  Google Scholar 

  • Masaki T, Matsumura K, Saito F, Sunada Y, Shimizu T, Yorifuji H, Motoyoshi K, Kamakura K (2000) Expression of dystroglycan and laminin-2 in peripheral nerve under axonal degeneration and regeneration. Acta Neuropathol 99:289–295

    PubMed  CAS  Google Scholar 

  • Mathews GA, ffrench-Constant C (1995) Embryonic fibronectins are up-regulated following peripheral nerve injury in rats. J Neurobiol 26:171–188

    PubMed  CAS  Google Scholar 

  • Miao T, Wu DS, Zhang Y, Bo XN, Subang MC, Wang P, Richardson PM (2006) Suppressor of cytokine signaling-3 suppresses the ability of activated signal transducer and activator of transcription-3 to stimulate neurite growth in rat primary sensory neurons. J Neurosci 26:9512–9519

    PubMed  CAS  Google Scholar 

  • Mirski R, Reichert F, Klar A, Rotshenker S (2003) Granulocyte macrophage colony stimulating factor (GM-CSF) activity is regulated by a GM-CSF binding molecule in Wallerian degeneration following injury to peripheral nerve axons. J Neuroimmunol 140:88–96

    PubMed  CAS  Google Scholar 

  • Mueller M, Leonhard C, Wacker K, Ringelstein EB, Okabe M, Hickey WF, Kiefer R (2003) Macrophage response to peripheral nerve injury: The quantitative contribution of resident and hematogenous macrophages. Lab Invest 83:175–185

    PubMed  Google Scholar 

  • Myers JP, Gomez TM (2011) Focal adhesion kinase promotes integrin adhesion dynamics necessary for chemotropic turning of nerve growth cones. J Neurosci 31:13585–13595

    PubMed  CAS  Google Scholar 

  • Nadeau S, Filali M, Zhang J, Kerr BJ, Rivest S, Soulet D, Iwakura Y, Vaccari JPD, Keane RW, Lacroix S (2011) Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1 beta and TNF: implications for neuropathic pain. J Neurosci 31:12533–12542

    PubMed  CAS  Google Scholar 

  • Narciso MS, Mietto BD, Marques SA, Soares CP, Mermelstein CD, El Cheikh MC, Martinez AMB (2009) Sciatic nerve regeneration is accelerated in galectin-3 knockout mice. Exp Neurol 217:7–15

    PubMed  CAS  Google Scholar 

  • Okada T, Ichikawa M, Tokita Y, Horie H, Saito K, Yoshida J, Watanabe M (2005) Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve. Exp Neurol 196:153–163

    PubMed  Google Scholar 

  • Omura T, Omura K, Sano M, Sawada T, Hasegawa T, Nagano A (2005) Spatiotemporal quantification of recruit and resident macrophages after crush nerve injury utilizing immunohistochemistry. Brain Res 1057:29–36

    PubMed  CAS  Google Scholar 

  • Ousman SS, David S (2000) Lysophosphatidylcholine induces rapid recruitment and activation of macrophages in the adult mouse spinal cord. Glia 30:92–104

    PubMed  CAS  Google Scholar 

  • Ousman SS, David S (2001) MIP-1 alpha, MCP-1, GM-CSF, and TNF-alpha control the immune cell response that mediates rapid phagocytosis of myelin from the adult mouse spinal cord. J Neurosci 21:4649–4656

    PubMed  CAS  Google Scholar 

  • Paveliev M, Lume M, Velthut A, Phillips M, Arumae U, Saarma M (2007) Neurotrophic factors switch between two signaling pathways that trigger axonal growth. J Cell Sci 120:2507–2516

    PubMed  CAS  Google Scholar 

  • Perrin FE, Lacroix S, Aviles-Trigueros M, David S (2005) Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha and interleukin-1 beta in Wallerian degeneration. Brain 128:854–866

    PubMed  Google Scholar 

  • Perry VH, Brown MC (1992) Role of macrophages in peripheral-nerve degeneration and repair. Bioessays 14:401–406

    PubMed  CAS  Google Scholar 

  • Perry VH, Brown MC, Lunn ER, Tree P, Gordon S (1990) Evidence that very slow Wallerian degeneration in C57Bl/Ola mice is an intrinsic property of the peripheral-nerve. Eur J Neurosci 2:802–808

    PubMed  CAS  Google Scholar 

  • Perry VH, Tsao JW, Fearn S, Brown MC (1995) Radiation-induced reductions in macrophage recruitment have only slight effects on myelin degeneration in sectioned peripheral-nerves of mice. Euro J Neurosci 7:271–280

    CAS  Google Scholar 

  • Pineau I, Lacroix S (2009) Endogenous signals initiating inflammation in the injured nervous system. Glia 57:351–361

    PubMed  Google Scholar 

  • Plantman S, Patarroyo M, Fried K, Domogatskaya A, Tryggvason K, Hammarberg H, Cullheim S (2008) Integrin-laminin interactions controlling neurite outgrowth from adult DRG neurons in vitro. Mol Cell Neurosci 39:50–62

    PubMed  CAS  Google Scholar 

  • Previtali SC, Feltri ML, Archelos JJ, Quattrini A, Wrabetz L, Hartung HP (2001) Role of integrins in the peripheral nervous system. Progress Neurobiol 64:35–49

    CAS  Google Scholar 

  • Ramaglia V, King RHM, Nourallah M, Wolterman R, de Jonge R, Ramkema M, Vigar MA, van der Wetering S, Morgan BP, Troost D, Baas F (2007) The membrane attack complex of the complement system is essential for rapid wallerian degeneration. J Neurosci 27:7663–7672

    PubMed  CAS  Google Scholar 

  • Reichert F, Saada A, Rotshenker S (1994) Peripheral-nerve injury induces schwann-cells to express 2 macrophage phenotypes - phagocytosis and the galactose-specific lectin Mac-2. J Neurosci 14:3231–3245

    PubMed  CAS  Google Scholar 

  • Reichert F, Levitzky R, Rotshenker S (1996) Interleukin 6 in intact and injured mouse peripheral nerves. Eur J Neurosci 8:530–535

    PubMed  CAS  Google Scholar 

  • Rotshenker S, Reichert F, Gitik M, Haklai R, Elad-Sfadia G, Kloog Y (2008) Galectin-3/MAC-2, Ras and PI3K activate complement receptor-3 and scavenger receptor-AI/II-mediated myelin phagocytosis in microglia. Glia 56:1607–1613

    PubMed  Google Scholar 

  • Ruohonen S, Tenhami M, Kylliainen LM, Roytta M (2005) Cytokine changes after peripheral nerve injury. J Peripher Nerv Syst 10:78

    Google Scholar 

  • Rutkowski JL, Tuite GF, Lincoln PM, Boyer PJ, Tennekoon GI, Kunkel SL (1999) Signals for proinflammatory cytokine secretion by human Schwann cells. J Neuroimmunol 101:47–60

    PubMed  CAS  Google Scholar 

  • Saada A, Reichert F, Rotshenker S (1996) Granulocyte macrophage colony stimulating factor produced in lesioned peripheral nerves induces the up-regulation of cell surface expression of MAC-2 by macrophages and Schwann cells. J Cell Biol 133:159–167

    PubMed  CAS  Google Scholar 

  • Saitoh F, Araki T (2010) Proteasomal degradation of glutamine synthetase regulates Schwann cell differentiation. J Neurosci 30:1204–1212

    PubMed  CAS  Google Scholar 

  • Sango K, Tokashiki A, Ajiki K, Horie M, Kawano H, Watabe K, Horie H, Kadoya T (2004) Synthesis, localization and externalization of galectin-1 in mature dorsal root ganglion neurons and Schwann cells. Eur J Neurosci 19:55–64

    PubMed  Google Scholar 

  • Scott ALM, Ramer MS (2010) Schwann cell p75(NTR) prevents spontaneous sensory reinnervation of the adult spinal cord. Brain 133:421–432

    PubMed  Google Scholar 

  • Shamash S, Reichert F, Rotshenker S (2002) The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta. J Neurosci 22:3052–3060

    PubMed  CAS  Google Scholar 

  • Shen YJ, DeBellard ME, Salzer JL, Roder J, Filbin MT (1998) Myelin-associated glycoprotein in myelin and expressed by Schwann cells inhibits axonal regeneration and branching. Mol Cell Neurosci 12:79–91

    PubMed  CAS  Google Scholar 

  • Sica A, Schioppa T, Mantovani A, Allavena P (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: Potential targets of anti-cancer therapy. Eur J Cancer 42:717–727

    PubMed  CAS  Google Scholar 

  • Siebert H, Sachse A, Kuziel WA, Maeda N, Bruck W (2000) The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system. J Neuroimmunol 110:177–185

    PubMed  CAS  Google Scholar 

  • Song XY, Zhou FHH, Zhong JH, Wu LLY, Zhou XF (2006) Knockout of p75(NTR) impairs re-myelination of injured sciatic nerve in mice. J Neurochem 96:833–842

    PubMed  CAS  Google Scholar 

  • Stam FJ, MacGillavry HD, Armstrong NJ, de Gunst MCM, Zhang Y, van Kesteren RE, Smit AB, Verhaagen J (2007) Identification of candidate transcriptional modulators involved in successful regeneration after nerve injury. Eur J Neurosci 25:3629–3637

    PubMed  Google Scholar 

  • Stoll G, Hartung HP (1992) The role of macrophages in degeneration and immune-mediated demyelination of the peripheral nervous-system. Adv Neuroimmunol 2:163–179

    Google Scholar 

  • Stoll G, Griffin JW, Li CY, Trapp BD (1989) Wallerian degeneration in the peripheral nervous-system - participation of both Schwann-cells and macrophages in myelin degradation. J Neurocytol 18:671–683

    PubMed  CAS  Google Scholar 

  • Subang MC, Richardson PM (2001) Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue. Eur J Neurosci 13:521–528

    PubMed  CAS  Google Scholar 

  • Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong ZY, Modlin RL, Akira S (2002) Cutting edge: Role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14

    PubMed  CAS  Google Scholar 

  • Tieu BC, Lee C, Sun H, LeJeune W, Recinos A, Ju XX, Spratt H, Guo DC, Milewicz D, Tilton RG, Brasier AR (2009) An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice. J Clin Invest 119:3637–3651

    PubMed  CAS  Google Scholar 

  • Toews AD, Barrett C, Morell P (1998) Monocyte chemoattractant protein 1 is responsible for macrophage recruitment following injury to sciatic nerve. J Neurosci Res 53:260–267

    PubMed  CAS  Google Scholar 

  • Tona A, Perides G, Rahemtulla F, Dahl D (1993) Extracellular-matrix in regenerating rat sciatic-nerve - a comparative-study on the localization of laminin, hyaluronic-acid, and chondroitin sulfate proteoglycans, including versican. J Histochem Cytochem 41:593–599

    PubMed  CAS  Google Scholar 

  • Touma E, Kato S, Fukui K, Koike T (2007) Calpain-mediated cleavage of collapsin response mediator protein(CRMP)-2 during neurite degeneration in mice. Eur J Neurosci 26:3368–3381

    PubMed  Google Scholar 

  • Tsao JW, George EB, Griffin JW (1999) Temperature modulation reveals three distinct stages of Wallerian degeneration. J Neurosci 19:4718–4726

    PubMed  CAS  Google Scholar 

  • Tucker BA, Mearow KM (2008) Peripheral sensory axon growth: from receptor binding to cellular signaling. Can J Neurol Sci 35:551–566

    PubMed  Google Scholar 

  • Tucker BA, Rahimtula M, Mearow KM (2006) Laminin and growth factor receptor activation stimulates differential growth responses in subpopulations of adult DRG neurons. Eur J Neurosci 24:676–690

    PubMed  Google Scholar 

  • Van der Zee CEEM, Kreft M, Beckers G, Kuipers A, Sonnenberg A (2008) v. J Neurosci 28:11292–11303

    PubMed  Google Scholar 

  • Vargas ME, Watanabe J, Singh SJ, Robinson WH, Barres BA (2010) Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury. PNAS 107:11993–11998

    PubMed  CAS  Google Scholar 

  • Viader A, Chang LW, Fahrner T, Nagarajan R, Milbrandt J (2011) MicroRNAs modulate Schwann cell response to nerve injury by reinforcing transcriptional silencing of dedifferentiation-related genes. J Neurosci 31:17358–17369

    PubMed  CAS  Google Scholar 

  • Vogelezang MG, Scherer SS, Fawcett JW, ffrench-Constant C (1999) Regulation of fibronectin alternative splicing during peripheral nerve repair. J Neurosci Res 56:323–333

    PubMed  CAS  Google Scholar 

  • Waller A (1850) Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations on the alterations produced thereby in the structure of their primitive fibers. Philos Trans R Soc Lond B 140:423–429

    Google Scholar 

  • Wallquist W, Patarroyo M, Thams S, Carlstedt T, Stark B, Cullheim S, Hammarberg H (2002) Laminin chains in rat and human peripheral nerve: Distribution and regulation during development and after axonal injury. J Comp Neurol 454:284–293

    PubMed  CAS  Google Scholar 

  • Wallquist W, Zelano J, Plantman S, Kaufman SJ, Cullheim S, Hammarberg H (2004) Dorsal root ganglion neurons up-regulate the expression of laminin-associated integrins after peripheral but not central axotomy. J Comp Neurol 480:162–169

    PubMed  CAS  Google Scholar 

  • Weerasuriya A, Mizisin AP (2011) The blood-nerve barrier: structure and functional significance. Methods Mol Biol 686:149–173

    PubMed  CAS  Google Scholar 

  • Werner A, Willem M, Jones LL, Kreutzberg GW, Mayer U, Raivich G (2000) Impaired axonal regeneration in alpha 7 integrin-deficient mice. J Neurosci 20:1822–1830

    PubMed  CAS  Google Scholar 

  • Xie XY, Barrett JN (1991) Membrane resealing in cultured rat septal neurons after neurite transection - evidence for enhancement by Ca2 + -triggered protease activity and cytoskeletal disassembly. J Neurosci 11:3257–3267

    PubMed  CAS  Google Scholar 

  • Yang DP, Zhang DP, Mak KS, Bonder DE, Pomeroy SL, Kim HA (2008) Schwann cell proliferation during Wallerian degeneration is not necessary for regeneration and remyelination of the peripheral nerves: axon-dependent removal of newly generated Schwann cells by apoptosis. Mol Cell Neurosci 38:80–88

    PubMed  CAS  Google Scholar 

  • Zamir E, Geiger B (2001) Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 114:3583–3590

    PubMed  CAS  Google Scholar 

  • Zhang JY, Luo XG, Xian CJ, Liu ZH, Zhou XF (2000) Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents. Eur J Neurosci 12:4171–4180

    PubMed  CAS  Google Scholar 

  • Zhong J, Dietzel ID, Wahle P, Kopf M, Heumann R (1999) Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice. J Neurosci 19:4305–4313

    PubMed  CAS  Google Scholar 

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  1. Molecular Neurobiology Laboratory, Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr 5, 40225, Düsseldorf, Germany

    Frank Bosse

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Bosse, F. Extrinsic cellular and molecular mediators of peripheral axonal regeneration. Cell Tissue Res 349, 5–14 (2012). https://doi.org/10.1007/s00441-012-1389-5

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