title: Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus.
abstract: The aim of this study was to characterize the microglial and astroglial reactions to degeneration of (a) hippocampal CA1 pyramidal cells and dentate hilar neurons induced by cerebral ischemia and (b) CA3 pyramidal cells and dentate hilar neurons induced by intraventricular injections of kainic acid (KA). The microglial reactions to ischemia, as monitored by histochemical staining for the enzyme nucleoside diphosphatase (NDPase) and immunohistochemical staining for the complement type 3 receptor (CR3), could be divided into (1) initial and generalized, but transient, reactions which also included areas devoid of subsequent neural degeneration and (2) protracted, degeneration-specific reactions in the areas with neural degeneration. Due to more widespread hippocampal involvement a similar distinction was not possible after KA lesions. After both ischemia and KA application the protracted degeneration-specific reactions were characterized by increased NDPase/CR3 reactivity and prominent morphological changes. In the dentate hilus, reactive microglial cells clustered around the degenerating hilar neurons. In stratum radiatum of CA1, reactive microglial cells transformed into either (1) "rod cells," aligned along the postischemic, degenerating pyramidal cell dendrites, followed by subsequent transformation into ameboid-like cells, or (2) "bushy" cells, in response to degeneration of Schaffer collaterals induced by KA lesioning of CA3 pyramidal cells. Within stratum radiatum of the KA-lesioned CA3, where both dendrites and axons were degenerating, the microglial cells developed into stellate cells with thickened, retracted processes and plump cell bodies. These cells were supplemented by rounded macrophage-like cells. Astroglial reactions, monitored by immunohistochemical staining for the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin (VIM), and the normal plasma constituent immunoglobulin G (IgG), showed an initial and generalized astroglial immunoreactivity for IgG, which paralleled the initial and transient microglial reactions, while the reactive changes in GFAP and VIM immunohistochemistry paralleled the protracted, degeneration-specific reactions with regard to timing, strength, and distribution. In the KA-lesioned CA3, the most prominent finding was a prompt loss of astroglial GFAP immunoreactivity corresponding to the degenerating pyramidal cell layer and the adjacent mossy fiber layer. The results strongly indicate that stimuli other than neural degeneration initiated the activation of both microglial and astroglial cells, which then upon further activation by actual neuronal damage and degeneration adjust according to which neuronal structures were undergoing degeneration.
authors.affiliation: PharmaBiotec, University of Copenhagen, Denmark.
authors.forename: M B
authors.initials: MB
authors.lastname: Jørgensen
authors.forename: B R
authors.initials: BR
authors.lastname: Finsen
authors.forename: M B
authors.initials: MB
authors.lastname: Jensen
authors.forename: B
authors.initials: B
authors.lastname: Castellano
authors.forename: N H
authors.initials: NH
authors.lastname: Diemer
authors.forename: J
authors.initials: J
authors.lastname: Zimmer
mesh_terms: D017766:Acid Anhydride Hydrolases; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007608:Kainic Acid; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling
chemical_list: D007074:Immunoglobulin G; D007381:Intermediate Filament Proteins; D016177:Macrophage-1 Antigen; D010744:Phosphoric Monoester Hydrolases; D017766:Acid Anhydride Hydrolases; C023837:nucleoside-diphosphatase; D007608:Kainic Acid