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Phenotypic diversity and kinetics of proliferating microglia and astrocytes following cortical stab wounds
Author(s) -
Amat José A.,
Ishiguro Hideaki,
Nakamura Kazuo,
Norton William T.
Publication year - 1996
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199604)16:4<368::aid-glia9>3.0.co;2-w
Subject(s) - microglia , glial fibrillary acidic protein , biology , neuroglia , astrocyte , immunostaining , pathology , gliosis , proliferating cell nuclear antigen , microbiology and biotechnology , bromodeoxyuridine , thymidine , immunology , neuroscience , immunohistochemistry , central nervous system , medicine , inflammation , biochemistry , in vitro
Brain injury induces reactive gliosis, characterized by increased expression of glial fibrillary acidic protein (GFAP), astrocytes hypertrophy, and hyperplasia of astrocytes and microglia. One hypothesis tested in this study was whether ganglioside G D3 + glial precursor cells would contribute to macroglial proliferation following injury. Adult rats received a cortical stab wound. Proliferating cells were identified by immunostaining for proliferating cell nuclear antigen (PCNA) and by [ 3 H]‐thymidine autoradiography, and cell phenotypes by immunocytochemical staining for G D3 , GFAP, ED1 (for reactive microglia) and for Bandeiraea Simplicifolia isolectin‐B 4 binding (all microglia). Animals were labeled with thymidine at 1, 2, 3, and 4 days postlesion (dpl) and sacrificed at various times thereafter. Proliferating cells of each phenotype were quantified. A dramatic upregulation of G D3 on ramified microglia was seen in the ipsilateral hemisphere by 2 dpl. Proliferating cells consisted of microglia and fewer astrocytes. Microglia proliferated maximally at 2–3 dpl and one third to one half were G D3 +. Astrocytes proliferated maximally at 3–4 dpl, and some were also G D3 +. Both ramified and ameboid forms of microglia proliferated and by 4 dpl all G D3 + microglia were ED1+ and vice versa. In the contralateral cortex microglia expressed neither G D3 nor ED1. Thus they acquired these antigens when activated. Neither microglia nor astrocytes that were thymidine‐labeled at 2, 3, or 4 dpl changed in number in subsequent days. Most thymidine+ astrocytes were large GFAP+ reactive cells that clearly arose from pre‐existing astrocytes, not from G D3 + glial precursors. In this model of injury microglia proliferate earlier and to a much greater extent than astrocytes, they can divide when in ramified form, and G D3 is up‐regulated in most reactive microglia and in a subset of reactive astrocytes. We also conclude that microglial proliferation precedes proliferation of invading blood‐borne macrophages. © 1996 Wiley‐Liss, Inc.