Microglial Cell Population Expansion Following Acute Neural Injury

  • M. Wirenfeldt
  • L. Dissing- Olesen
  • A. A. Babcock
  • R. Ladeby
  • M. B. Jensen
  • T. Owens
  • Bente Finsen

By studying the response of hippocampal microglia to anterograde axonal and terminal degeneration in the dentate gyrus we have identified several subsets of microglia, including immigrant bone marrow (BM)-derived and resident microglia, and resident microglia expressing different levels of CD34, of which the majority were induced to undergo proliferation upon injury. Based on the population kinetics elucidated until now, we have evidence that a subpopulation of microglial cells may undergo repeated proliferation upon injury while some microglial cells may not proliferate at all within the investigated period. Furthermore, resident cells in the mouse may be supplemented by BM-derived cells. A picture emerges where new cells are being born, while other cells, including the newly generated and recruited cells are beginning to be cleared from the site of lesion, at least partly by apoptotic mechanisms. Increased insight into basic microglial cell biology may improve diagnostic and therapeutic possibilities for patients suffering from conditions that are currently without real treatment options.


Microglial Cell Dentate Gyrus Microglial Activation Perforant Path Microglial Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

11. References

  1. Acarin, L., Vela, J.M., Gonzalez, B. and Castellano, B., 1994, Demonstration of poly-N-acetyl lactosamine residues in ameboid and ramified microglial cells in rat-brain by tomato lectin- binding. J. Histochem. Cytochem. 42: 1033.PubMedGoogle Scholar
  2. Albini, T.A., Wang, R.C., Reiser, B., Zamir, E., Wu, G.S. and Rao, N.A., 2005, Microglial stability and repopulation in the retina. Br. J. Ophthalmol. 89: 901.PubMedGoogle Scholar
  3. Allan, S.M. and Rothwell, N.J., 2001, Cytokines and acute neurodegeneration. Nat. Rev. Neurosci. 2: 734.PubMedGoogle Scholar
  4. Andrews, R.G., Singer, J.W. and Bernstein, I.D., 1986, Monoclonal-antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors. Blood 67: 842.PubMedGoogle Scholar
  5. Archelos, J.J., Jung, S., Maurer, M., Schmied, M., Lassmann, H., Tamatani, T., Miyasaka, M., Toyka, K.V. and Hartung, H.P., 1993, Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1. Ann. Neurol. 34: 145.PubMedGoogle Scholar
  6. Asheuer, M., Pflumio, F.O., Benhamida, S., Dubart-Kupperschmitt, A., Fouquet, F., Imai, Y., Aubourg, P. and Cartier, N., 2004, Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein. Proc. Natl Acad. Sci. USA 110: 3557.Google Scholar
  7. Babcock, A.A., Kuziel, W.A., Rivest, S. and Owens, T., 2003, Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J. Neurosci. 23: 7922.PubMedGoogle Scholar
  8. Bartholdi, D. and Schwab, M.E., 1997, Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: An in situ hybridization study. Eur. J. Neurosci. 9: 1422.PubMedGoogle Scholar
  9. Bechmann, I., Goldmann, J., Kovac, A.D., Kwidzinski, E., Simburger, E., Naftolin, F., Dirnagl, U., Nitsch, R., and Priller, J., 2005, Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia. FASEB J. 6: 647.Google Scholar
  10. Berenson, R.J., Andrews, R.G., Bensinger, W.I., Kalamasz, D., Knitter, G., Buckner, C.D. and Bernstein, I.D., 1988, Antigen Cd34+ marrow-cells engraft lethally irradiated baboons. J. Clin. Invest. 81: 951.PubMedGoogle Scholar
  11. Bianchin, M.M., Capella, H.M., Chaves, D.L., Steindel, M., Grisard, E.C., Ganev, G.G., da Silva, J.P., Neto, E.S., Poffo, M.A., Walz, R., Carlotti, C.G. and Sakamoto, A.C., 2004, Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy - PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects. Cell. Mol. Neurobiol. 24: 1.PubMedGoogle Scholar
  12. Biffi, A., De Palma, M., Quattrini, A., Del Carro, U., Amadio, S., Visigalli, I., Sessa, M., Fasano, S., Brambilla, R., Marchesini, S., Bordignon, C. and Naldini, L., 2004, Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells. J. Clin. Invest. 113: 1118.PubMedGoogle Scholar
  13. Brown, J., Greaves, M.F. and Molgaard, H.V., 1991, The gene encoding the stem-cell antigen, Cd34, is conserved in mouse and expressed in hematopoietic progenitor-cell lines, brain, and embryonic fibroblasts. Int. Immunol. 3: 175.PubMedGoogle Scholar
  14. Cammermeyer, J., 1965, Juxtavascular karyokinesis and microglia cell proliferation during retrograde reaction in the mouse facial nucleus. Ergeb. Anat. Entwicklungsgesch. 38: 1.PubMedGoogle Scholar
  15. Carson, M.J., Reilly, C.R., Sutcliffe, J.G. and Lo, D., 1998, Mature microglia resemble immature antigen-presenting cells. Glia 22: 72.PubMedGoogle Scholar
  16. Carson, M.J., Sutcliffe, J.G. and Campbell, I.L., 1999, Microglia stimulate naive T-cell differentiation without stimulating T-cell proliferation. J. Neurosci. Res. 55: 127.PubMedGoogle Scholar
  17. Castellano, B., Gonzalez, B., Jensen, M.B., Pedersen, E.B., Finsen, B.R. and Zimmer, J., 1991, A double staining technique for simultaneous demonstration of astrocytes and microglia in brain sections and astroglial cell-cultures. J. Histochem. Cytochem. 39: 561.PubMedGoogle Scholar
  18. Cella, M., Buonsanti, C., Strader, C., Kondo, T., Salmaggi, A. and Colonna, M., 2003, Impaired differentiation of osteoclasts in TREM-2-deficient individuals. J. Exp. Med. 198: 645.PubMedGoogle Scholar
  19. Chopp, M., Li, Y., Jiang, N., Zhang, R.L., and Prostak, J., 1996, Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. J. Cereb. Blood Flow Metab. 16: 578.PubMedGoogle Scholar
  20. Civin, C.I., Strauss, L.C., Brovall, C., Fackler, M.J., Schwartz, J.F. and Shaper, J.H., 1984, Antigenic analysis of hematopoiesis 3: A hematopoietic progenitor-cell surface-antigen defined by a monoclonal-antibody raised against Kg-1A Cells. J. Immunol. 133: 157.PubMedGoogle Scholar
  21. Cogle, C.R., Yachnis, A.T., Laywell, E.D., Zander, D.S., Wingard, J.R., Steindler, D.A. and Scott, E.W., 2004, Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet 363: 1432.PubMedGoogle Scholar
  22. Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S., Littman, D.R., Dustin, M.L. and Gan, W.B., 2005, ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8: 752.PubMedGoogle Scholar
  23. de Jong, E.K., Dijkstra, I.M., Hensen, M., Brouwer, N., van Amerongen, M., Liem, R.S., Boddeke, H.W. and Biber, K., 2005, Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion. J. Neurosci. 25: 7548.PubMedGoogle Scholar
  24. del Rio-Hortega, P., 1932, Microglia. In: Cytology and Cellular Pathology of the Nervous System. W. Penfield, ed., Paul B. Hoeber, New York, pp. 481-534.Google Scholar
  25. Engelhardt, B. and Ransohoff, R.M., 2005, The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 26: 485.PubMedGoogle Scholar
  26. Fagan, A.M. and Gage, F.H., 1990, Cholinergic sprouting in the hippocampus: a proposed role for IL-1. Exp. Neurol. 110: 105.PubMedGoogle Scholar
  27. Ferrari, D., Villalba, M., Chiozzi, P., Falzoni, S., Ricciardi-Castagnoli, P. and DiVirgilio, F., 1996, Mouse microglial cells express a plasma membrane pore gated by extracellular ATP. J. Immunol. 156: 1531.PubMedGoogle Scholar
  28. Finsen, B.R., Jorgensen, M.B., Diemer, N.H. and Zimmer, J., 1993a, Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult-rat hippocampus. Glia 7: 41.PubMedGoogle Scholar
  29. Finsen, B.R., Tonder, N., Xavier, G.F., Sorensen, J.C. and Zimmer, J., 1993b, Induction of microglial immunomolecules by anterogradely degenerating mossy fibers in the rat hippocampal-formation J. Chem. Neuroanat. 6: 267.Google Scholar
  30. Ford, A.L., Goodsall, A.L., Hickey, W.F. and Sedgwick, J.D., 1995, Normal adult ramified microglia separated from other central-nervous-system macrophages by flow cytometric sorting - phenotypic differences defined and direct ex-vivo antigen presentation to myelin basic protein-reactive Cd4(+) T-cells compared. J. Immunol. 154: 4309.PubMedGoogle Scholar
  31. Furuya, T., Tanaka, R., Urabe, T., Hayakawa, J., Migita, M., Shimada, T., Mizuno, Y. and Mochizuki, H., 2003, Establishment of modified chimeric mice using GFP bone marrow as a model for neurological disorders. Neuroreport 14: 629.PubMedGoogle Scholar
  32. Garden, G.A., 2002, Microglia in human immunodeficiency virus-associated neurodegeneration. Glia 40: 240.PubMedGoogle Scholar
  33. Gaugler, M.H., Squiban, C., Mouthon, M.A., Gourmelon, P. and van der Meeren, A., 2001, Irradiation enhances the support of haemopoietic cell transmigration, proliferation and differentiation by endothelial cells. Br. J. Haematol. 113: 940.PubMedGoogle Scholar
  34. Gowans, J.L. and Knight, E.J., 1964, Route of re-circulation of lymphocytes in rat. Proc. R. Soc. Lond. Biol. Sci. 159: 257.Google Scholar
  35. Graeber, M.B. and Mehraein, P., 1994, Microglial rod cells. Neuropathol. Appl. Neurobiol. 20: 178.PubMedGoogle Scholar
  36. Graeber, M.B., Streit, W.J. and Kreutzberg, G.W., 1988a, Axotomy of the rat facial-nerve leads to increased Cr3 complement receptor expression by activated microglial cells. J. Neurosci. Res. 21: 18.PubMedGoogle Scholar
  37. Graeber, M.B., Tetzlaff, W., Streit, W.J. and Kreutzberg, G.W., 1988b, Microglial cells but not astrocytes undergo mitosis following rat facial-nerve axotomy. Neurosci. Lett. 85: 317.PubMedGoogle Scholar
  38. Greenwood, J., Amos, C.L., Walters, C.E., Couraud, P.O., Lyck, R., Engelhardt, B. and Adamson, P., 2003, Intracellular domain of brain endothelial intercellular adhesion molecule-1 is essential for T lymphocyte-mediated signaling and migration. J. Immunol. 171: 2099.PubMedGoogle Scholar
  39. Greter, M., Heppner, F.L., Lemos, M.P., Odermatt, B.M., Goebels, N., Laufer, T., Noelle, R.J. and Becher, B., 2005, Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat. Med. 11: 328.PubMedGoogle Scholar
  40. Hailer, N.P., Bechmann, I., Heizmann, S. and Nitsch, R., 1997, Adhesion molecule expression on phagocytic microglial cells following anterograde degeneration of perforant path axons. Hippocampus 7: 341.PubMedGoogle Scholar
  41. Hailer, N.P., Grampp, A. and Nitsch, R., 1999, Proliferation of microglia and astrocytes in the dentate gyrus following entorhinal cortex lesion: a quantitative bromodeoxyuridine-labelling study. Eur. J. Neurosci. 11: 3359.PubMedGoogle Scholar
  42. Hallenbeck, J.M., 2002, The many faces of tumor necrosis factor in stroke. Nat. Med. 8: 1363.PubMedGoogle Scholar
  43. Harrison, J.K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R.K., Streit, W.J., Salafranca, M.N., Adhikari, S., Thompson, D.A., Botti, P., Bacon, K.B. and Feng, L., 1998, Role for neuronally derived fractalkine in mediating interactions between neurons and CXCR1-expressing microglia. Proc. Natl Acad. Sci. USA 95: 10861.Google Scholar
  44. He, J.L., Chen, Y.Z., Farzan, M., Choe, H.Y., Ohagen, A., Gartner, S., Busciglio, J., Yang, X.Y., Hofmann, W., Newman, W., Mackay, C.R., Sodroski, J. and Gabuzda, D., 1997, CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature 385: 645.PubMedGoogle Scholar
  45. Hickey, W.F. and Kimura, H., 1988, Perivascular microglial cells of the CNS are bone-marrow derived and present antigen in-vivo. Science 239: 290.PubMedGoogle Scholar
  46. Hoek, R.M., Ruuls, S.R., Murphy, C.A., Wright, G.J., Goddard, R., Zurawski, S.M., Blom, B., Homola, M.E., Streit, W.J., Brown, M.H., Barclay, A.N. and Sedgwick, J.D., 2000, Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290: 1768.PubMedGoogle Scholar
  47. Honda, S., Sasaki, Y., Ohsawa, K., Imai, Y., Nakamura, Y., Inoue, K. and Kohsaka, S., 2001, Extracellular ATP or ADP induce chemotaxis of cultured microglia through G(i/o)-coupled P2Y receptors. J. Neurosci. 21: 1975.PubMedGoogle Scholar
  48. Jenmalm, M.C., Cherwinski, H., Bowman, E.P., Phillips, J.H. and Sedgwick, J.D., 2006, Regulation of myeloid cell function through the CD200 Receptor. J. Immunol. 176: 191.PubMedGoogle Scholar
  49. Jensen, M.B., Gonzalez, B., Castellano, B. and Zimmer, J., 1994, Microglial and astroglial reactions to anterograde axonal degeneration - a histochemical and immunocytochemical study of the adult-rat fascia-dentata after entorhinal perforant path lesions. Exp. Brain Res. 98: 245.PubMedGoogle Scholar
  50. Jensen, M.B., Finsen, B. and Zimmer, J., 1997, Morphological and immunophenotypic microglial changes in the denervated fascia dentata of adult rats: correlation with blood-brain barrier damage and astroglial reactions. Exp. Neurol. 143: 103.PubMedGoogle Scholar
  51. Jensen, M.B., Hegelund, I.V., Poulsen, F.R., Owens, T., Zimmer, J. and Finsen, B., 1999, Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentate. Neuroscience 93: 507.PubMedGoogle Scholar
  52. Jensen, M.B., Poulsen, F.R. and Finsen, B., 2000, Axonal sprouting regulates myelin basic protein gene expression in denervated mouse hippocampus. Int. J. Dev. Neurosci. 18: 221.PubMedGoogle Scholar
  53. Jones, L.L., Banati, R.B., Graeber, M.B., Bonfanti, L., Raivich, G. and Kreutzberg, G.W., 1997, Population control of microglia: does apoptosis play a role? J. Neurocyt. 26: 755.Google Scholar
  54. Jones, L.L., Kreutzberg, G.W. and Raivich, G., 1998, Transforming growth factor beta’s 1, 2 and 3 inhibit proliferation of ramified microglia on astrocyte monolayer. Brain Res. 795: 301.PubMedGoogle Scholar
  55. Jorgensen, M.B., Finsen, B.R., Jensen, M.B., Castellano, B., Diemer, N.H. and Zimmer, J., 1993, Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult-rat hippocampus. Exp. Neurol. 120: 70.PubMedGoogle Scholar
  56. Kato, H., Takahashi, A. and Itoyama, Y., 2003, Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat. Brain Res. Bull. 60: 215.PubMedGoogle Scholar
  57. Kiefer, R., Lindholm, D. and Kreutzberg, G.W., 1993, Interleukin-6 and transforming growth-factor-beta-1 messenger-RNAs are induced in rat facial nucleus following motoneuron axotomy. Eur. J. Neurosci. 5: 775.PubMedGoogle Scholar
  58. Klein, M.A., Moller, J.C., Jones, L.L., Bluethmann, H., Kreutzberg, G.W. and Raivich, G., 1997, Impaired neuroglial activation in interleukin-6 deficient mice. Glia 19: 227.PubMedGoogle Scholar
  59. Kloss, C.U.A., Kreutzberg, G.W. and Raivich, G., 1997, Proliferation of ramified microglia on an astrocyte monolayer: characterization of stimulatory and inhibitory cytokines, J. Neurosci. Res. 49: 248.PubMedGoogle Scholar
  60. Kreutzberg, G.W., 1966, Autoradiographische untersuchung uber die beteiligung von gliazellen an der axonalen reaktion im facialiskern der ratte. Acta Neuropathol. (Berl.) 7: 149.Google Scholar
  61. Ladeby, R., Wirenfeldt, M., Dalmau, I., Gregersen, R., Garcia-Ovejero, D., Babcock, A., Owens, T. and Finsen, B., 2005a, Proliferating resident microglia express the stem cell antigen CD34 in response to acute neural injury. Glia 50: 121.PubMedGoogle Scholar
  62. Ladeby, R., Wirenfeldt, M., Garcia-Ovejero, D., Fenger, C., Dissing-Olesen, L., Dalmau, I. and Finsen, B., 2005b, Microglial cell population dynamics in the injured adult central nervous system. Brain Res. Brain Res. Rev. 48: 196.PubMedGoogle Scholar
  63. Lambertsen, K.L., Gregersen, R. and Finsen, B., 2002, Microglial-macrophage synthesis of tumor necrosis factor after focal cerebral ischemia in mice is strain dependent. J. Cereb. Blood Flow Metab. 22: 785.PubMedGoogle Scholar
  64. Lassmann, H. and Hickey, W.F., 1993, Radiation bone-barrow chimeras as a tool to study microglia turnover in normal brain and inflammation. Clin. Neuropathol. 12: 284.PubMedGoogle Scholar
  65. Lawson, L.J., Perry, V.H. and Gordon, S., 1992, Turnover of resident microglia in the normal adult-mouse brain. Neuroscience 48: 405.PubMedGoogle Scholar
  66. Lehrmann, E., Kiefer, R., Christensen, T., Toyka, K.V., Zimmer, J., Diemer, N.H., Hartung, H.P. and Finsen, B., 1998, Microglia and macrophages are major sources of locally produced transforming growth factor beta(1) after transient middle cerebral artery occlusion in rats. Glia 24: 437.PubMedGoogle Scholar
  67. Matsumoto, Y. and Fujiwara, M., 1987, Absence of donor-type major histocompatibility complex class-I antigen-bearing microglia in the rat central-nervous-system of radiation bone-marrow chimeras. J. Neuroimmunol. 17: 71.PubMedGoogle Scholar
  68. Matthews, D.A., Cotman, C. and Lynch, G., 1976, Electron-microscopic study of lesion-induced synaptogenesis in dentate gyrus of adult rat .1. Magnitude and time course of degeneration. Brain Res. 115: 1.PubMedGoogle Scholar
  69. Morgan, T.E., Nichols, N.R., Pasinetti, G.M. and Finch, C.E., 1993, TGF-beta 1 mRNA increases in macro-phage/microglial cells of the hippocampus in response to deafferentiation and kainic acid-induced neuro-degeneration. Exp. Neurol. 120: 291.PubMedGoogle Scholar
  70. Mori, S. and Leblond, C.P., 1969, Identification of microglia in light and electron microscopy. J. Comp. Neurol. 135: 57.PubMedGoogle Scholar
  71. Morioka, T., Kalehua, A.N. and Streit, W.J., 1991, The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J. Cereb. Blood Flow Metab. 11: 966.PubMedGoogle Scholar
  72. Nimmerjahn, A., Kirchhoff, F. and Helmchen, F., 2005, Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308: 1314.PubMedGoogle Scholar
  73. Nissl, F., 1899, Ueber einige beziehungen zwischen nervenzellenerkrankungen und gliösen erscheinungen bei verschiedenen psychosen. Arch. Psychiatr. 32: 656.Google Scholar
  74. Noseworthy, J.H., Lucchinetti, C., Rodriguez, M. and Weinshenker, B.G., 2000, Medical progress: multiple sclerosis. New Eng. J. Med. 343: 938.Google Scholar
  75. Novikoff, A.B. and Goldfischer, S., 1961, Nucleosidediphosphatase activity in Golgi apparatus and its usefulness for cytological studies. Proc. Natl Acad. Sci. USA 47: 802.PubMedGoogle Scholar
  76. O’Keefe, G.M., Nguyen, V.T. and Benveniste, E.N., 2002, Regulation and function of class II major histocompatibility complex, CD40, and B7 expression in macrophages and microglia: implications in neurological diseases. J. Neurovir. 8: 496.Google Scholar
  77. Pakkenberg, B. and Gundersen, H.J.G., 1988, Total number of neurons and glial-cells in human-brain nuclei estimated by the dissector and the fractionator. J. Microscopy. Oxford. 150: 1.Google Scholar
  78. Pennell, N.A. and Streit, W.J., 1998, Tracing of fluoro-gold prelabeled microglia injected into the adult rat brain. Glia 23: 84.PubMedGoogle Scholar
  79. Perry, V.H., Hume, D.A. and Gordon, S., 1985, Immunohistochemical localization of macrophages and microglia in the adult and developing mouse-brain. Neuroscience 15: 313.PubMedGoogle Scholar
  80. Persson, L., Hansson, H.A. and Sourander, P., 1976, Extravasation, spread and cellular uptake of Evans blue-labelled albumin around a reproducible small stab-wound in the rat brain. Acta Neuropathol. (Berl.) 34: 125.Google Scholar
  81. Popovich, P.G. and Hickey, W.E., 2001, Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord. J. Neuropathol. Exp. Neurol. 60: 676.PubMedGoogle Scholar
  82. Priller, J., Flugel, A., Wehner, T., Boentert, M., Haas, C.A., Prinz, M., Fernandez-Klett, F., Prass, K., Bechmann, I., de Boer, B.A., Frotscher, M., Kreutzberg, G.W., Persons, D.A. and Dirnagl, U., 2001, Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment. Nat. Med. 7: 1356.PubMedGoogle Scholar
  83. Raivich, G., 2005, Like cops on the beat: the active role of resting microglia. Trends Neurosci. 28: 571.PubMedGoogle Scholar
  84. Raivich, G., Morenoflores, M.T., Moller, J.C. and Kreutzberg, G.W., 1994, Inhibition of posttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor deficiency in the mouse. Eur. J. Neurosci. 6: 1615.PubMedGoogle Scholar
  85. Raivich, G., Haas, S., Werner, A., Klein, M.A., Kloss, C. and Kreutzberg, G.W., 1998, Regulation of MCSF receptors on microglia in the normal and injured mouse central nervous system: a quantitative immuno-fluorescence study using confocal laser microscopy. J. Comp. Neurol. 395: 342.PubMedGoogle Scholar
  86. Raivich, G., Bohatschek, M., Kloss, C.U.A., Werner, A., Jones, L.L. and Kreutzberg, G.W., 1999, Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Res. Rev. 30: 77.PubMedGoogle Scholar
  87. Rao, K. and Lund, R.D., 1989, Degeneration of optic axons induces the expression of major histocompatibility antigens. Brain Res. 488: 332.PubMedGoogle Scholar
  88. Rappert, A., Bechmann, I., Pivneva, T., Mahlo, J., Biber, K., Nolte, C., Kovac, A.D., Gerard, C., Boddeke, H.W.G.M., Nitsch, R. and Kettenmann, H., 2004, CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion. J. Neurosci. 24: 8500.PubMedGoogle Scholar
  89. Rogove, A.D., Lu, W. and Tsirka, S.E., 2002, Microglial activation and recruitment, but not proliferation, suffice to mediate neurodegeneration. Cell. Death Differ. 9: 801.PubMedGoogle Scholar
  90. Sedgwick, J.D., Schwender, S., Imrich, H., Dorries, R., Butcher, G.W. and Termeulen, V., 1991, Isolation and direct characterization of resident microglial cells from the normal and inflamed central-nervous-system. Proc. Natl Acad. Sci. USA 88: 7438.PubMedGoogle Scholar
  91. Stoll, G., Trapp, B.D. and Griffin, J.W., 1989, Macrophage function during Wallerian degeneration of rat optic nerve: clearance of degenerating myelin and Ia expression. J. Neurosci. 9: 2327.PubMedGoogle Scholar
  92. Streit, W.J., 1990, An improved staining method for rat microglial cells using the lectin from griffonia-simplicifolia (GSA I-B4). J. Histochem. Cytochem. 38: 1683.PubMedGoogle Scholar
  93. Streit, W.J., 2000, Microglial response to brain injury: A brief synopsis. Toxicol. Pathol. 28: 28.PubMedGoogle Scholar
  94. Streit, W.J., 2004, Microglia and Alzheimer’s disease pathogenesis. J. Neurosci. Res. 77: 1.PubMedGoogle Scholar
  95. Streit, W.J. and Kreutzberg, G.W., 1988, Response of endogenous glial-cells to motor neuron degeneration induced by toxic ricin. J. Comp. Neurol. 268: 248.PubMedGoogle Scholar
  96. Streit, W.J., Semple-Rowland, S.L., Hurley, S.D., Miller, R.C., Popovich, P.G. and Stokes, B.T., 1998, Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. Exp. Neurol. 152: 74.PubMedGoogle Scholar
  97. Streit, W.J., Walter, S.A. and Pennell, N.A., 1999, Reactive microgliosis. Prog. Neurobiol. 57: 563.PubMedGoogle Scholar
  98. Takahashi, K., Rochford, C.D.P. and Neumann, H., 2005, Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J. Exp. Med. 201: 647.PubMedGoogle Scholar
  99. Ting, P., Masaoka, H., Kuroiwa, T., Wagner, H., Fenton, I. and Klatzo, I., 1986, Influence of blood-brain barrier opening to proteins on development of post-ischaemic brain injury. Neurol. Res. 8: 146.PubMedGoogle Scholar
  100. Vallieres, L. and Sawchenko, P.E., 2003, Bone marrow-derived cells that populate the adult mouse brain preserve their hematopoietic identity. J. Neurosci. 23: 5197.PubMedGoogle Scholar
  101. Walz, W., Ilschner, S., Ohlemeyer, C., Banati, R. and Kettenmann, H., 1993, Extracellular ATP activates a cation conductance and a K+ conductance in cultured microglial cells from mouse-brain. J. Neurosci. 13: 4403.PubMedGoogle Scholar
  102. Wirenfeldt, M., Babcock, A.A., Ladeby, R., Lambertsen, K.L., Dagnaes-Hansen, F., Leslie, R.G., Owens, T. and Finsen, B., 2005a, Reactive microgliosis engages distinct responses by microglial subpopulations after minor central nervous system injury. J. Neurosci. Res. 82: 507.PubMedGoogle Scholar
  103. Wirenfeldt, M., Ladeby, R., Dalmau, I., Banati, R.B. and Finsen, B., 2005b, Microglia - biology and relevance to disease. Ugeskr. Laeger. 82: 507.Google Scholar
  104. Wolburg, H., Wolburg-Buchholz, K. and Engelhardt, B., 2005, Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol. (Berl.) 109: 181.Google Scholar
  105. Young, P.E., Baumhueter, S. and Lasky, L.A., 1995, The sialomucin CD34 is expressed on hematopoietic-cells and blood-vessels during murine development. Blood 85: 96.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • M. Wirenfeldt
    • 1
  • L. Dissing- Olesen
    • 1
  • A. A. Babcock
    • 1
  • R. Ladeby
    • 1
  • M. B. Jensen
    • 1
  • T. Owens
    • 1
  • Bente Finsen
    • 1
  1. 1.Medical Biotechnology CenterUniversity of Southern DenmarkDenmark

Personalised recommendations