Neurochemical Research

, Volume 38, Issue 10, pp 1996–2008 | Cite as

Glial Cells Activation Potentially Contributes to the Upregulation of Stromal Cell-Derived Factor-1α After Optic Nerve Crush in Rats

  • Xi-Tao Yang
  • Dong-Chao Pan
  • Er-Tao Chen
  • Yong-Yan Bi
  • Dong-Fu Feng
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

Stromal cell-derived factor-1α (SDF-1α) plays an important role after injury. However, little is known regarding its temporal and spatial expression patterns or how it interacts with glial cells after optic nerve crush injury. We characterized the temporal and spatial expression pattern of SDF-1α in the retina and optic nerve following optic nerve crush and demonstrated that SDF-1α is localized to the glial cells that are distributed in the retina and optic nerve. CXCR4, the receptor for SDF-1α, is expressed along the ganglion cell layer (GCL). The relative expression levels of Sdf-1α mRNA and SDF-1α protein in the retina and optic nerve 1, 2, 3, 5, 7, 10 and 14 days after injury were determined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, respectively, and the Cxcr4 mRNA expression was determined using real-time PCR. Immunofluorescence and immunohistochemical approaches were used to detect the localization of SDF-1α and CXCR4 after injury. The upregulation of Sdf-1α and Cxcr4 mRNA was detected as early as day one after injury in the retina and day two in the optic nerve, the expression peaks 5–7 days after injury. The expression of Sdf-1α and Cxcr4 mRNA was maintained for at least 14 days after the optic nerve crush injury. Furthermore, SDF-1α-positive zones were distributed locally in the reactive glial cells, which suggested potential autocrine stimulation. CXCR4 was mainly expressed in the GCL, which was also adjacent to the the glial cells. These findings suggest that following optic nerve crush, the levels of endogenous SDF-1α and CXCR4 increase in the retina and optic nerve, where activated glial cells may act as a source of increased SDF-1α protein.

Keywords

Chemokines Retina Optic nerve Glial cells Optic nerve crush 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81171796) and Shanghai Science and Technology Commission (09ZR1417500).

Conflict of interest

None of the authors has any conflict of interest to disclose.

References

  1. 1.
    Mackay CR (2001) Chemokines: immunology’s high impact factors. Nat Immunol 2:95–101PubMedCrossRefGoogle Scholar
  2. 2.
    Youn BS, Mantel C, Broxmeyer HE (2000) Chemokines, chemokine receptors and hematopoiesis. Immunol Rev 177:150–174PubMedCrossRefGoogle Scholar
  3. 3.
    Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242PubMedCrossRefGoogle Scholar
  4. 4.
    Nomura M, Matsuda Y, Itoh H et al (1996) Genetic mapping of the mouse stromal cell-derived factor gene (Sdf1) to mouse and rat chromosomes. Cytogenet Cell Genet 73:286–289PubMedCrossRefGoogle Scholar
  5. 5.
    Shirozu M, Nakano T, Inazawa J (1995) Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics 28:495–500PubMedCrossRefGoogle Scholar
  6. 6.
    Janowski M (2009) Functional diversity of SDF-1 splicing variants. Cell Adh Migr 3:243–249PubMedCrossRefGoogle Scholar
  7. 7.
    Lu M, Grove EA, Miller RJ (2002) Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci USA 99:7090–7095PubMedCrossRefGoogle Scholar
  8. 8.
    Lai P, Li T, Yang J, Xie C et al (2008) Upregulation of stromal cell-derived factor 1 (SDF-1) expression in microvasculature endothelial cells in retinal ischemia-reperfusion injury. Graefes Arch Clin Exp Ophthalmol 246:1707–1713PubMedCrossRefGoogle Scholar
  9. 9.
    Ji JF, He BP, Dheen ST et al (2004) Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells 22:415–427PubMedCrossRefGoogle Scholar
  10. 10.
    Ratajczak MZ, Zuba-Surma E, Kucia M et al (2006) The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia 20:1915–1924PubMedCrossRefGoogle Scholar
  11. 11.
    Imitola J, Raddassi K, Park KI et al (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101:18117–18122PubMedCrossRefGoogle Scholar
  12. 12.
    Itoh T, Satou T, Ishida H et al (2009) The relationship between SDF-1alpha/CXCR4 and neural stem cells appearing in damaged area after traumatic brain injury in rats. Neurol Res 31:90–102PubMedCrossRefGoogle Scholar
  13. 13.
    Berkelaar M, Clarke DB, Wang YC (1994) Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J Neurosci 14:4368–4374PubMedGoogle Scholar
  14. 14.
    Quigley HA, Nickells RW, Kerrigan LA et al (1995) Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 36:774–786PubMedGoogle Scholar
  15. 15.
    Bien A, Seidenbecher CI, Böckers TM et al (1999) Apoptotic versus necrotic characteristics of retinal ganglion cell death after partial optic nerve injury. J Neurotrauma 16:153–163PubMedCrossRefGoogle Scholar
  16. 16.
    Tezel G, Yang X, Yang J et al (2004) Role of tumor necrosis factor receptor-1 in the death of retinal ganglion cells following optic nerve crush injury in mice. Brain Res 996:202–212PubMedCrossRefGoogle Scholar
  17. 17.
    Bar-Ilan A, Naveh N, Weissman C et al (1991) Prostaglandin E2 changes in the retina and optic nerve of an eye with injured optic nerve. Neuroscience 45:221–225PubMedCrossRefGoogle Scholar
  18. 18.
    Chalasani SH, Sabol A, Xu H et al (2007) Stromal cell-derived factor-1 antagonizes slit/robo signaling in vivo. J Neurosci 27:973–980PubMedCrossRefGoogle Scholar
  19. 19.
    Salcedo R, Oppenheim JJ (2003) Role of chemokines in angiogenesis: CXCL12/SDF-1 and CXCR4 interaction, a key regulator of endothelial cell responses. Microcirculation 10:359–370PubMedCrossRefGoogle Scholar
  20. 20.
    Miller JT, Bartley JH, Wimborne HJ et al (2005) The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury. BMC Neurosci 6:63PubMedCrossRefGoogle Scholar
  21. 21.
    Lima e Silva R, Shen J, Hackett SF et al (2007) The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types of ocular neovascularization. FASEB J 21:3219–3230PubMedCrossRefGoogle Scholar
  22. 22.
    Ceradini DJ, Kulkarni AR, Callaghan MJ et al (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10:858–864PubMedCrossRefGoogle Scholar
  23. 23.
    Feng DF, Chen ET, Li XY et al (2010) Standardizing optic nerve crushes with an aneurysm clip. Neurol Res 32:476–481PubMedCrossRefGoogle Scholar
  24. 24.
    Lewis GP, Fisher SK (2003) Up-regulation of glial fibrillary acidic protein in response to retinal injury: its potential role in glial remodeling and a comparison to vimentin expression. Int Rev Cytol 230:263–290PubMedCrossRefGoogle Scholar
  25. 25.
    Tysseling VM, Mithal D, Sahni V et al (2011) SDF1 in the dorsal corticospinal tract promotes CXCR4 + cell migration after spinal cord injury. J Neuroinflammation 8:16PubMedCrossRefGoogle Scholar
  26. 26.
    Miotke JA, MacLennan AJ et al (2007) Immunohistochemical localization of CNTFRalpha in adult mouse retina and optic nerve following intraorbital nerve crush: evidence for the axonal loss of a trophic factor receptor after injury. J Comp Neurol 500:384–400PubMedCrossRefGoogle Scholar
  27. 27.
    Battisti WP, Wang J, Bozek K et al (1995) Macrophages, microglia, and astrocytes are rapidly activated after crush injury of the goldfish optic nerve: a light and electron microscopic analysis. J Comp Neurol 54:306–320CrossRefGoogle Scholar
  28. 28.
    Blaugrund E, Duvdevani R, Lavie V et al (1992) Disappearance of astrocytes and invasion of macrophages following crush injury of adult rodent optic nerves: implications for regeneration. Exp Neurol 118:105–115PubMedCrossRefGoogle Scholar
  29. 29.
    Frank M, Wolburg H (1996) Cellular reactions at the lesion site after crushing of the rat optic nerve. Glia 16:227–240PubMedCrossRefGoogle Scholar
  30. 30.
    Salvador-Silva M, Vidal-Sanz M, Villegas-Pérez MP (2000) Microglial cells in the retina of Carassius auratus: effects of optic nerve crush. J Comp Neurol 417:431–447PubMedCrossRefGoogle Scholar
  31. 31.
    Sellés-Navarro I, Ellezam B, Fajardo R et al (2001) Retinal ganglion cell and nonneuronal cell responses to a microcrush lesion of adult rat optic nerve. Exp Neurol 167:282–289PubMedCrossRefGoogle Scholar
  32. 32.
    Bianchi R, Kastrisianaki E, Giambanco I et al (2011) S100B Protein Stimulates Microglia Migration via RAGE-dependent Up-regulation of Chemokine Expression and Release. J Biol Chem 286:7214–7226PubMedCrossRefGoogle Scholar
  33. 33.
    Stumm RK, Rummel J, Junker V et al (2002) A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci 22:5865–5878PubMedGoogle Scholar
  34. 34.
    Butler JM, Guthrie SM, Koc M et al (2005) SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest 115:86–93PubMedGoogle Scholar
  35. 35.
    Orimo A, Gupta PB, Sgroi DC et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–348PubMedCrossRefGoogle Scholar
  36. 36.
    Deshane J, Chen S, Caballero S et al (2007) Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism. J Exp Med 204:605–618PubMedCrossRefGoogle Scholar
  37. 37.
    Yamaguchi J, Kusano KF, Masuo O (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 107:1322–1328PubMedCrossRefGoogle Scholar
  38. 38.
    Hiasa K, Ishibashi M, Ohtani K et al (2004) Gene transfer of stromal cell-derived factor-1αlpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation 109:2454–2461PubMedCrossRefGoogle Scholar
  39. 39.
    Li Q, Shirabe K, Thisse C et al (2005) Chemokine signaling guides axons within the retina in zebrafish. J Neurosci 25:1711–1717PubMedCrossRefGoogle Scholar
  40. 40.
    Fleming JC, Norenberg MD, Ramsay DA et al (2006) The cellular inflammatory response in human spinal cords after injury. Brain 129:3249–3269PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Xi-Tao Yang
    • 1
  • Dong-Chao Pan
    • 1
  • Er-Tao Chen
    • 1
  • Yong-Yan Bi
    • 1
  • Dong-Fu Feng
    • 1
    • 2
  1. 1.Department of Neurosurgery, Shanghai Third People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Institute of Traumatic MedicineShanghai Jiaotong University School of MedicineShanghaiChina

Personalised recommendations