Reaction of astrocytes in the gerbil hippocampus following transient ischemia: Immunohistochemical observations with antibodies against glial fibrillary acidic protein, glutamine synthetase, and S-100 protein

https://doi.org/10.1016/0014-4886(92)90006-CGet rights and content

Abstract

An immunohistochemical method was used to study the distribution and changes with time of the astrocytic reaction in the gerbil hippocampus following transient ischemia. Three markers were investigated with specific antibodies to glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and S-100 protein. On Day 2 after ischemia, and more prominently on Day 3, reactive astrocytes were intensely stained for GFAP in the hippocampal formation, especially in the CA1 region and dentate gyrus. This response by astrocytes preceded CA1 pyramidal cell degeneration, which became apparent on Day 5. On Day 5, immunoreactive cells were not stained as intensely as on Day 3, but cells in the CA1 region and dentate gyrus were still more intensely stained than those in normal animals. GS and S-100 showed similar changes in distribution after ischemia, although the change in GS was less prominent: the hilus of the dentate gyrus was most intensely stained. Both immunoreactivities seemed to increase rather transiently on Day 2 or 3 and to decrease to the initial level on Day 5. The fact that reactive astrocytes appeared in CA1 before the onset of visible neural degeneration indicates that signals from indisposed neurons may be transmitted to astrocytes for their quick functioning. It is also suggested that degenerative changes occur in the dentate gyrus and may be involved in the delayed neural death of CA1 pyramidal cells. These observations indicate that astrocytes play a role in the neural degeneration induced by ischemia and that several types of astrocytes seem to react differently.

References (46)

  • Y. Takamiya et al.

    Possible association of platelet-derived growth factor (PDGF) with the appearance of reactive astrocytes following brain injury in situ

    Brain Res.

    (1986)
  • E. Westerberg et al.

    Excitatory amino acid receptors and ischemic brain damage in the rat

    Neurosci. Lett.

    (1987)
  • H. Arai et al.

    Energy metabolism in delayed neuronal death of CA1 neurons of the hippocampus following transient ischemia in the gerbil

    Metab. Brain Dis.

    (1986)
  • T. Babiak et al.

    Increased mitochondrial area in astrocytes following cerebral ischemia

    J. Neuropathol. Exp. Neurol.

    (1980)
  • H. Benveniste et al.

    Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis

    J. Neurochem.

    (1984)
  • A. Bignami et al.

    The astroglial response to stabbing. Immunofluorescence studies with antibodies to astrocyte-specific protein (GFA) in mammalian and submammalian verterbrates

    Neuropathol. Appl. Neurobiol.

    (1976)
  • W. Bodsch et al.

    Selective neuronal vulnerability to cerebral protein- and RNA-synthesis in the hippocampus of the gerbil brain

  • M. du Bois et al.

    Cell proliferation after ischemic injury in gerbil brain. An immunocytochemical and autoradiographic study

    Cell Tissue Res.

    (1985)
  • D. Cocchia

    Immunocytochemical localization of S-100 protein in the brain of adult rat. An ultrastructural study

    Cell Tissue Res.

    (1981)
  • B.J. Crain et al.

    Electron microscopic study of the gerbil dentate gyrus after transient forebrain ischemia

    Acta Neuropathol.

    (1990)
  • A. Crockard et al.

    Cerebral blood flow and edema following carotid occlusion in the gerbil

    Stroke

    (1980)
  • J. Deleo et al.

    Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the mongolian gerbil and protection by propentofylline

    J. Cereb. Blood Flow Metab.

    (1987)
  • M. Didier et al.

    Differential immunocytochemical staining for glial fibrillary acidic (GFA) protein, S-100 protein and glutamine synthetase in the rat subcommissural organ, nonspecialized ventricular ependyma and adjacent neuropil

    Cell Tissue Res.

    (1986)
  • Cited by (78)

    • Genomic approach to selective vulnerability of the hippocampus in brain ischemia-hypoxia

      2015, Neuroscience
      Citation Excerpt :

      Taken together, the difference between CA1 and CA3 is relative, and it is observed after short periods of ischemia, as would occur in cardiac arrest with survival under clinical conditions. Numerous studies have used immunohistochemical markers for astrocytes and microglial cells after global brain ischemia (Petito et al., 1990; Schmidt-Kastner et al., 1990; Morioka et al., 1991, 1992; Tanaka et al., 1992; Jørgensen et al., 1993; Ordy et al., 1993; Sugawara et al., 2002). As a simplification, the response of astrocytes and microglial cells in CA1 starts early after ischemia and becomes prominent when neurons become necrotic.

    • Severity of middle cerebral artery occlusion determines retinal deficits in rats

      2014, Experimental Neurology
      Citation Excerpt :

      By 9 days post-MCAO, GS levels returned to normal, suggesting that GS may clear all of the excess glutamate and allow for recovery of retinal function. Similarly, increases in GS have been observed from 3 h to 3 days after cerebral ischemia (Hoshi et al., 2006; Petito et al., 1992; Tanaka et al., 1992; Verma et al., 2010), and these increases appear to be transient, returning to baseline levels by 5 days (Tanaka et al., 1992). Additionally, treatments that enhance the activity of glutamate transporter (Verma et al., 2010) and GS (Zhang et al., 2011) have been shown to reduce brain injury in ischemia-reperfusion models, providing further support for a protective role of GS in reducing levels of extracellular glutamate after ischemic injury.

    View all citing articles on Scopus
    View full text