title: Morphological and immunophenotypic microglial changes in the denervated fascia dentata of adult rats: correlation with blood-brain barrier damage and astroglial reactions.
abstract: The reactions of microglial and astroglial cells to anterograde axonal degeneration were studied in the fascia dentata of adult rats from 1 to 42 days after removal of the entorhinal perforant path projection. The observations focused on the kinetics of glial activation in terms of induction of immunomolecules on the glial cells and the possible correlation between these changes and lesion-induced extravasation of plasma constituents. Normal and activated microglial cells were identified by immunohistochemical visualization of the constitutively expressed complement type 3 receptor (CR3/CD11b). Activated microglial cells were stained immunohistochemically for the inducible major histocompatibility complex (MHC) antigen class I and class II and the leukocyte common antigen LCA/CD45). Astroglial cells were identified by immunohistochemical staining for glial fibrillary acidic protein (GFAP). Blood-brain barrier (BBB) conditions were primarily evaluated by immunohistochemical staining for extravasated Immunoglobulin G (IgG), but also by intravenously injected horseradish peroxidase (HRP) and Evans Blue. Twenty-four hours after entorhinal cortex ablation, microglial cells in the perforant path terminal zones displayed an increase in CR3 immunoreactivity, changes of morphology and an induced expression of MHC antigen class I. At the same time there was a hitherto undescribed leakage of IgG through the BBB (albeit without detectable extravasation of HRP and Evans Blue). One day later microglial cells also expressed LCA, but MHC antigen class II was not induced under these degenerative conditions. The activation of microglial cells occurred prior to a noticeable hypertrophy of astroglial cells and increase in GFAP immunoreactivity, as this first became evident on Postlesional Day 2. From the results we conclude (1) that perforant path axonal degeneration induces an endothelial transcytosis of blood-borne IgG by mechanisms which cannot be envisioned by conventional HRP tracer methods and (2) that the early activation of both microglial cells and astroglial cells is likely to be initiated and later influenced by both axonal degeneration and extravasated plasma constituents. The demonstration of an early induction of immunomolecules on activated microglial cells and extravasation of blood borne molecules might moreover form the basis for a correspondingly early intervention aiming to regulate microglial immunomolecule, cytokine, and growth factor gene expression in the affected areas.
authors.affiliation: PharmaBiotec, Department of Anatomy and Cell Biology, University of Odense, Denmark.
authors.forename: M B
authors.initials: MB
authors.lastname: Jensen
authors.forename: B
authors.initials: B
authors.lastname: Finsen
authors.forename: J
authors.initials: J
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology*; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar