Skip to main content
SpringerLink
Log in

Redistribution of glutamate and GABA in the cerebral neocortex and hippocampus of the mongolian gerbil after transient ischemia

An immunocytochemical study

  • Original Articles
  • Published:
Molecular and Chemical Neuropathology

Abstract

The redistribution of glutamate and GABA in postischemic brains was examined immunocytochemically using the gerbil model of unilateral 1 h cerebral ischemia. In the cerebral neocortex, the majority of neurons underwent recovery processes after 5 h of recirculation, while neurons in the hippocampus were irreversibly damaged. Glutamate-like immunoreactivity (LI) was highly increased in the degenerating hippocampal CA3 pyramidal cells after recirculation, while in the neocortex and the hippocampal CA1 sector, the pyramidal cells showed only slightly increased glutamate-LI. GABA-LI-positive punctae in the neuropil, corresponding to neuronal processes of GABAergic neurons, were accentuated after recirculation both in the cerebral neocortex and the hippocampus. Although the astrocytes on the non-ischemic side showed neither glutamate-LI nor GABA-LI, the swollen astrocytes and their foot processes, which were observed after recirculation, often showed strong glutamate-LI and GABA-LI. These data suggest (1) the accumulation of glutamate or glutamate-like substances, especially in the CA3 pyramidal cells, (2) the excitation of the GABAergic neurons and their subsequent uptake of GABA, and (3) the sequestration of the extracellular neurotransmitters by astrocytes in the postischemic period.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Benveniste H., Drejer J., Schousboe A., and Diemer N. H. (1984) Elevation of the extracellular concentration of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis.J. Neurochem. 43, 1369–1374.

    Article  PubMed  CAS  Google Scholar 

  • Bernasconi R., Klein M., Martin P., Portet Ch., Maître L., Jones R. S. G., Baltzer V., and Schumtz, M. (1985) The specific protective effect of diazepam and valproate against isoniazid-induced seizures is not correlated with increased GABA levels.J. Neural Transmission 63, 169–189.

    Article  CAS  Google Scholar 

  • Blomqvist A. and Broman J. (1988) Light and electron microscopic immunohistochemical demonstration of GABA-immunoreactive astrocytes in the brain stem of the rat.J. Neurocytol. 17, 629–637.

    Article  PubMed  CAS  Google Scholar 

  • Chagnaud J.-L., Campistron G., and Geffard M. (1989) Monoclonal antibody directed against glutaraldehyde conjugated glutamate and immunocytochemical applications in the rat brain.Brain Res. 481, 175–189.

    Article  PubMed  CAS  Google Scholar 

  • Cocito L, Favale E., and Reni L. (1982) Epileptic seizures in cerebral arterial occlusive disease.Stroke 13, 189–195.

    PubMed  CAS  Google Scholar 

  • Cooper J. R., Bloom F. E., and Roth R. H. (1991) Amino acid transmiters, inThe Biochemical Basis of Neuropharmacology 6th ed., pp. 133–189, Oxford University Press, New York.

    Google Scholar 

  • Drejer J., Benveniste H., Diemer N. H., and Schousboe A. (1985) Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro.J. Neurochem. 45, 145–151.

    Article  PubMed  CAS  Google Scholar 

  • Francis A. and Pulsinelli W. (1982) The response of GABAergic and cholinergic neurons to transient cerebral ischemia.Brain Res. 243, 271–278.

    Article  PubMed  CAS  Google Scholar 

  • Fykse E. M. and Fonnum F. (1988) Uptake of γ-aminobutyric acid by synaptic vesicle fraction isolated from rat brain.J. Neurochem. 50, 1237–1242.

    Article  PubMed  CAS  Google Scholar 

  • Gamrani H., Onteniente B., Seguela P., Geffard M., and Calas A. (1986) Gamma-aminobutyric acid-immunoreactivity in the rat hippocampus. A light and electron microscopic study with anti-GABA antibodies.Brain Res. 364, 30–38.

    Article  PubMed  CAS  Google Scholar 

  • Hagberg H., Lehmann A., Sandberg M., Nyström B., Jacobson I., and Hamberger A. (1985) Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments.J. Cereb. Blood Flow Metab. 5, 413–419.

    PubMed  CAS  Google Scholar 

  • Henn F. A. and Hamberger A. (1971) Glial cell function: uptake of transmitter substances.Proc. Natl. Acad. Sci. USA 68, 2686–2690.

    Article  PubMed  CAS  Google Scholar 

  • Hillered L., Hallström A., Segersvärd S., Persson L., and Ungerstedt U. (1989) Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis.J. Cereb. Blood Flow Metab. 9, 607–616.

    PubMed  CAS  Google Scholar 

  • Hyde J. C. and Robinson N. (1974) Localization of sites of GABA catabolism in the rat retina.Nature 248, 432–433.

    Article  PubMed  CAS  Google Scholar 

  • Ito U., Spatz M., Walker J. T., and Klatzo I. (1975) Experimental cerebral ischemia in Mongolian gerbils.Acta Neuropathol. 32, 209–223.

    Article  PubMed  CAS  Google Scholar 

  • Johansen F. F., Jørgensen M. B., and Diemer N. H. (1983) Resistance of hippocampal CA-1 interneurons to 20 min of transient cerebral ischimia in the rat.Acta Neuropathol. 61, 135–140.

    Article  Google Scholar 

  • Johansen F. F., Sørensen T., Tønder N., Zimmer J., and Diemer N. H. (1992) Ultrastructure of neurons containing somatostatin in the dentate hilus of the rat hippocampus after cerebral ischemia, and a note on their commisural connections.Neuropathol. Appl. Neurobiol. 18, 189–200.

    Article  Google Scholar 

  • Kahn K. (1972) The natural course of experimental cerebral infarction in the gerbil.Neurology 22, 510–515.

    PubMed  CAS  Google Scholar 

  • Kolluri V. R. S. and Lakshmi G. Y. C. V. S. (1989) Changes in regional levels of putative neurotransmitter amino acids in brain under unilateral forebrain ischemia.Neurochem. Res. 14, 621–625.

    Article  PubMed  CAS  Google Scholar 

  • Lehmann A., Hagberg H., Jacobson I., and Hamberger A. (1985) Effects of status epilepticus on extracellular amino acids in the hippocampus.Brain Res. 359, 147–151.

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Hernandez A., Bell K. P., and Norenberg M. D. (1977) Glutamine synthetase: glial localization in brain.Science 195, 1356–1358.

    Article  PubMed  CAS  Google Scholar 

  • Meinecke D. L. and Peters A. (1987) GABA immunoreactive neurons in rat visual cortex.J. Comp. Neurol. 261, 388–404.

    Article  PubMed  CAS  Google Scholar 

  • Meldrum B. S., Swan J. H., Ottersen O. P., and Storm-Mathisen J. (1987) Redistribution of transmitter amino acids in rat hippocampus and cerebellum during seizures induced by L-allylglycine and bicuculline: an immunocytochemical study with antisera against conjugated GABA, glutamate and aspartate.Neuroscience 22, 17–27.

    Article  PubMed  CAS  Google Scholar 

  • Meyer F. B. (1989) Calcium, neuronal hyperexcitability and ischemic injury.Brain Res. Brain Res. Rev. 14, 227–243.

    Article  PubMed  CAS  Google Scholar 

  • Monaghan D. T., Holets V. R., Toy D. W., and Cotman C. W. (1983) Anatomical distribution of four pharmacologically distinct3H-L-glutamate binding sites.Nature 306, 176–179.

    Article  PubMed  CAS  Google Scholar 

  • Neal M. J., Cunningham J., Shah M. A., and Yazulla S. (1989) Immunocytochemical evidence that vigabatrin in rats causes GABA accumulation in glial cells of the retina.Neurosci. Lett. 98, 29–32.

    Article  PubMed  CAS  Google Scholar 

  • Nishikawa Y., Takahashi T., and Shimoda A. (1989) Morphological studies on cerebral cortical lesions induced by transient ischemia in Mongolian gerbil—Diffuse and peripheral pallor of the neuronal perikarya.Acta Neuropathol. 78, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Nitsch C., Goping G., and Klatzo I. (1989) Preservation of GABAergic perikarya and boutons after transient ischemia in the gerbil hippocampal CA1 field.Brain Res. 495, 243–252.

    Article  PubMed  CAS  Google Scholar 

  • Ottersen O. P. and Storm-Mathisen J. (1984) Glutamate- and GABA-containing neurons in the mouse and rat brain, as demonstrated with a new immunocytochemical technique.J. Comp. Neurol. 229, 374–392.

    Article  PubMed  CAS  Google Scholar 

  • Ottersen O. P., Torp R., and Storm-Mathisen J. (1989) New aspects of the pathogenesis of ischemic brain damage. Possible involvement of excitatory amino acids.Tidsskr. Nor Loegeforen. (in Norwegian)109. 2674–2677.

    CAS  Google Scholar 

  • Rothman S. M. and Olney J. W. (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage.Ann. Neurol. 19, 105–111.

    Article  PubMed  CAS  Google Scholar 

  • Schlander M., Hoyer S., and Frotscher M. (1988) Glutamate decarboxylase-immunoreactive neurons in the aging rat hippocampus are more resistant to ischemia than CA1 pyramidal cells.Neurosci. Lett. 91, 241–246.

    Article  PubMed  CAS  Google Scholar 

  • Schon F. and Kelly J. S. (1975) Selective uptake of [3H] β-alanine by glia: Association with the glial uptake system for GABA.Brain Res. 86, 243–257.

    Article  PubMed  CAS  Google Scholar 

  • Schousboe A., Wu J.-W., and Roberts E. (1973). Purification and characterization of the 4-aminobutyrate-2-ketoglutarate transaminase from mouse brain.Biochemistry 12, 2868–2873.

    Article  PubMed  CAS  Google Scholar 

  • Sekine Y., Hashimoto T., and Obata K. (1992) Stimulus-transcription coupling can be studied by in situ hybridization of brain slice preparation. Selective c-fos expression in hippocampal CA3 pyramidal cells.Proc. Japan. Acad., Ser. B. 68, 191–195.

    Article  Google Scholar 

  • Sihra T. S. and Nicholls D. G. (1987) 4-Aminobutyrate can be released exocytotically from guinea-pig cerebral cortical synaptosomes.J. Neurochem. 49, 261–267.

    Article  PubMed  CAS  Google Scholar 

  • Sloviter R. S. and Dimiano B. P. (1981) Sustained electrical stimulation of the perforant path duplicates kainate-induced electrophysiological effects and hippocampal damage in rats.Neurosci. Lett. 24, 279–284.

    Article  PubMed  CAS  Google Scholar 

  • Smith M.-L., Bendek G., Dahlgren N., Rosen I., Wieloch T., and Siesjö B. K. (1984) Models for studying long-term recovery following forebrain ischemia in the rat. 2. A 2-vessel occlusion model.Acta Neurol. Scand. 69, 385–401.

    Article  PubMed  CAS  Google Scholar 

  • Storm-Mathisen J. and Iversen L. L. (1974) Uptake of [3H]glutamic acid in excitatory nerve endings: light and electronmicroscopic observations in the hippocampal formation of the rat.Neuroscience 4, 1237–1253.

    Article  Google Scholar 

  • Storm-Mathisen J. and Wold J. E. (1981) In vivo high-affinity uptake and axonal transport of D-[2,3-3H]aspartate in excitory neurons.Brain Res. 230, 427–433.

    Article  PubMed  CAS  Google Scholar 

  • Storm-Mathisen J., Leknes A. K., Bore A. T., Vaaland J. L., Edminson P., Haug F.-M. S., and Ottersen O. P. (1983) First visualization of glutamate and GAGA in neurones by immunocytochemistry.Nature 301, 517–520.

    Article  PubMed  CAS  Google Scholar 

  • Storm-Mathisen J., Ottersen O. P., Fu-Long T., Gundersen V., Laake J. H., and Nordbo G. (1986) Metabolism and transport of amino acids studied by immunocytochemistry.Med. Biol. 64, 127–132.

    PubMed  CAS  Google Scholar 

  • Sutherland G., Peeling J., Lesiuk H., and Saunders J. (1990) Experimental, cerebral ischemia studied using nuclear magnetic resonance imaging and spectroscopy.J. Can. Assoc. Radiol.,41, 24–31.

    CAS  Google Scholar 

  • Tursky T. and Lassánová M. (1978) Inhibition of different molecular forms of brain glutamic acid decarboxylase (GAD) with ATP.J. Neurochem. 30, 903–905.

    Article  PubMed  CAS  Google Scholar 

  • van Gelder N. M. (1983) Metabolic interactions between neurons and astroglia: glutamine synthetase, carbonic anhydrase and water balance, inBasic Mechanisms of Neuronal Excitability (Jasper H. H., and van Gelder N. M., eds.), pp. 5–29, Liss, New York.

    Google Scholar 

  • Vinores S. A., Herman M. M., Rubinstein L. J., and Marangos P. J. (1984) Electron microscopic localization of neuron-specific enolase in rat and mouse brain.J. Histochem. Cytochem. 32, 1295–1302.

    PubMed  CAS  Google Scholar 

  • Watson A. H. D. (1988) Antibodies against GABA and glutamate label neurons with morphologically distinct synaptic vesicles in the locust central nervous system.Neuroscience 26, 33–44.

    Article  PubMed  CAS  Google Scholar 

  • Whetsell W. O., Jr., and Shapira N. A. (1993) Neuroexcitation, excitotoxicity and human neurological disease.Lab. Invest. 68, 372–387.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Asahikawa Medical College, Nishikagura 4-5, 078, Asahikawa, Japan

    Yuji Nishikawa, Tatsuro Takahashi & Katsuhiro Ogawa

Authors
  1. Yuji Nishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatsuro Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katsuhiro Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishikawa, Y., Takahashi, T. & Ogawa, K. Redistribution of glutamate and GABA in the cerebral neocortex and hippocampus of the mongolian gerbil after transient ischemia. Molecular and Chemical Neuropathology 22, 25–41 (1994). https://doi.org/10.1007/BF03160092

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03160092

Index Entries

Search

Navigation