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Polyamines and NMDA receptors modulate pericapillary astrocyte swelling following cerebral cryo-injury in the rat

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Journal of Neurocytology

Summary

Four hours following cryo-injury rat cerebral pericapillary astrocytes from the perilesional area were markedly swollen occupying 17% of the pericapillary space as compared to 11% in sham operated controls. Ornithine decarboxylase activity and polyamine levels were increased over sham controls. The astrocytic swelling, the percentage of the pericapillary space occupied by astrocytic processes, and polyamine levels were reduced to near control levels by the following: (1) α-difluoromethylornithine; (2) Ifenprodil; and (3) MK-801. α-Difluoromethylornithine is a specific inhibitor of ornithine decarboxylase, Ifenprodil is an inhibitor of the polyamine binding site on the n-methyl-d-aspartate receptor, and MK-801 is an antagonist to n-methyl-d-aspartate binding to the n-methyl-d-aspartate receptor. Addition of putrescine, the product of ornithine decarboxylase activity, reversed the effect of α-difluoromethylornithine and restored the pericapillary swelling. Putrescine did not affect the MK-801-induced reduction in pericapillary astrocytic swelling. Therefore, polyamines and the n-methyl-d-aspartate receptor modulate excitotoxic responses to cryo-injury in pericapillary cerebral astrocytes.

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References

  • Barres, B. A., Chun, L. L. Y. &Corey, S. P. (1990a) Ion channels in vertebrate glia.Annual Review of Neuroscience 13, 441–74.

    Google Scholar 

  • Barres, B. A., Koroshetz, W. J., Swartz, K. J., Chun, L. L. Y. &Corey, D. (1990b) Ion channel expression by white matter glia: the O-2A glial progenitor cell.Neuron 4, 507–24.

    Google Scholar 

  • Barron, K. D., Dentinger, M. P., Kimelberg, H. K., Nelson, L. R., Bourke, R. S., Kegan, S., Mankes, R. &Cragoe, E. J., Jr (1988) Ultrastructural features of a brain injury model in Cat. 1. Vascular and neurological changes and the prevention of astroglial swelling by a fluorenyl (aryloxy) alkanoic acid derivative (L-644, 711).Acta Neuropathologica 75, 295–307.

    Google Scholar 

  • Benveniste, H., Drejer, J., Schousboe, A. &Diemer, N. H. (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis.Journal of Neurochemistry 43, 1369–74.

    Google Scholar 

  • Bowman, C. L. &Kimelberg, H. K. (1984) Excitatory amino acids directly depolarize rat brain astrocytes in primary cultures.Nature 311, 656–9.

    Google Scholar 

  • Carter, C., Rivy, J. -P. &Scatton, B. (1989) Ifenprodil and SL 82.0715 are antagonists at the polyamine site of the N-methyl-D-aspartate (NMDA) receptor.European Journal of Pharmacology 64, 611–12.

    Google Scholar 

  • Chan, P. H. &Chu, L. (1989) Ketamine protects cultured astrocytes from glutamate-induced swelling.Brain Research 487, 380–3.

    Google Scholar 

  • Chan, P. H., Fishman, R. A., Lee, J. L. &Candelise, L. (1979) Effects of excitatory neurotransmitter amino acids on swelling of rat brain cortical slices.Journal of Neurochemistry 22, 1309–15.

    Google Scholar 

  • Choi, D. W. (1988) Glutamate neurotoxicity and diseases of the nervous system.Neuron 1, 623–34.

    Google Scholar 

  • Haglid, K. G., Wang, S., Hamberger, A., Lehmann, A. &Moller, C. J. (1991) Neuronal and glial marker proteins in the evaluation of the protective action of MK-801.Journal of Neurochemistry 56, 1957–61.

    Google Scholar 

  • Hertz, L. (1978) An intense potassium uptake into astrocytes, its further enhancement by high concentrations of potassium and its possible involvement in potassium homeostasis at the cellular level.Brain Research 145, 202–8.

    Google Scholar 

  • Hertz, L., Goldstein, M. H. &Hamberger, A. C. (1974) Uptake of the neurotransmitter candidate glutamate by glia.Nature 299, 663–4.

    Google Scholar 

  • Kettenman, H. &Schachner, M. (1985) Pharmacological properties of GABA, glutamate and aspartate induced depolarizations in cultured astrocytes.Journal of Neuroscience 5, 3295–301.

    Google Scholar 

  • Kimbelberg, H. (1987) Anisotonic media and glutamateinduced ion transport and volume responses in primary astrocyte cultures.Journal de Physiologie 82, 294–303.

    Google Scholar 

  • Kimelberg, H., Jalonen, T. &Walz, W. (1993) Regulation of the brain microenvironment: transmitters and ions. InAstrocytes: Pharmacology and Function (edited byMurphy, S.) pp. 193–228. New York: Academic Press.

    Google Scholar 

  • Koenig, H., Goldstone, A. D. &Lu, C. Y. (1989) Blood-brain barrier breakdown in cold-injured brain is linked to a biphasic stimulation of ornithine decarboxylase activity and polyamine synthesis: both are coordinately inhibited by verapamil, dexamethasone, and aspirin.Journal of Neurochemistry 52, 101–9.

    Google Scholar 

  • Koenig, H., Goldstone, A. D., Lu, C. Y., Trout, J. J. &Iqbal, Z. (1991) NMDA receptors on brain capillary mediate cold injury-induced activation of polyamine synthesis and blood-brain barrier breakdown.Society for Neuroscience Abstracts 17, 7.

    Google Scholar 

  • Koenig, H., Trout, J. J., Goldstone, A. D. &Lu, C. Y. (1992a) Capillary NMDA receptors regulate blood-brain barrier function and breakdown.Brain Research 588, 297–303.

    Google Scholar 

  • Koenig, H., Trout, J. J., Goldstone, A. D. &Lu, C. Y. (1992b) NMDA receptors mediate activation of polyamine synthesis and blood-brain barrier breakdown after cold injury. InThe Role of Neurotransmitters in Brain Injury. (edited byGlobus, M. T. &Dietrich, W. D.) pp. 279–83. New York: Plenum Press.

    Google Scholar 

  • Lowry, O. H., Rosenbrough, N. J., Farr, A. L. &Randall, R. J. (1951) Protein measurement with the Polin phenol reagent.Journal of Biological Chemistry 193, 265–75.

    Google Scholar 

  • Matyja, E. (1986) Morphologic evidence of a primary response of glia to kainic acid administration into the rat neostriatum: studiedin vivo andin vitro.Experimental Neurology 92, 609–23.

    Google Scholar 

  • McCarthy, K. D., Salm, A. &Lerea, L. S. (1988) Astroglial receptors and their regulation of intermediate filament protein phosphorylation. InGlial Cell Receptors. (edited byKimelberg, H. K.) pp. 1–22. New York: Raven Press.

    Google Scholar 

  • Nag, S. &Riopelle, R. J. (1990) Spinal neuronal pathology associated with continuous intrathecal infusion of N-methyl-D-aspartate in the rat.Acta Neuropathologica 81, 7–13.

    Google Scholar 

  • Olney, J. W., Ho, O. L. &Rhee, C. (1971) Cytotoxic effects of acidic and sulfur containing amino acids on the infant mouse central nervous system.Experimental Brain Research 14, 61–76.

    Google Scholar 

  • Petito, C. K., Morgello, S., Felix, J. C. &Lesser, M. L. (1990) The two patterns of reactive astrocytosis in postischemic brain.Journal of Cerebral Blood Flow and Metabolism 10, 850–859.

    Google Scholar 

  • Reynolds, I. J. &Miller, R. J. (1989) Ifenprodil is a novel type of N-methyl-D-aspartate receptor antagonist: interaction with polyamines.Molecular Pharmacology 36, 758–65.

    Google Scholar 

  • Rothman, S. M. &Olney, J. J. (1987) Excitotoxicity and the NMDA receptor.Trends in Neurosciences 10, 299–302.

    Google Scholar 

  • Sontheimer, H., Kettenmann, H., Backus, K. H. &Schachner, M. (1988) Glutamate opens Na+/K+ channels in cultured astrocytes.Glia 1, 328–36.

    Google Scholar 

  • Teichberg, V. I. (1991) Glial glutamate receptors: likely actors in brain signaling.FASEB Journal 5, 3086–91.

    Google Scholar 

  • Travis, J. (1994) Glia: the brain's other cells.Science 266, 970–72.

    Google Scholar 

  • Trout, J. J., Koenig, H., Goldstone, A. D. &Lu, C. Y. (1986) Blood-brain barrier breakdown by cold injury: polyamine signals mediate acute stimulation of endocytosis, vesicular transport and microvillus formation in rat cerebral capillaries.Laboratory Investigation 55, 622–31.

    Google Scholar 

  • Trout, J. J., Koenig, H., Goldstone, A. D., Iqbal, Z., Lu, C. Y. &Siddiqui, F. (1993) N-Methyl-D-aspartate receptor excitotoxicity involves activation of polyamine synthesis: protection by α-difluoromethylornithine.Journal of Neurochemistry 60, 353–5.

    Google Scholar 

  • Usowicz, M. M., Gallo, V. &Cull-Candy, S. G. (1989) Multiple conductance channels in type 2 cerebellar astrocytes activated by excitatory amino acids.Nature 229, 380–3.

    Google Scholar 

  • Williams, K., Romand, C. &Molinoff, P. B. (1989) Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-D-asparate receptor: pharmacological evidence for the existence of a polyamine binding site.Molecular Pharmacology 36, 575–81.

    Google Scholar 

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Authors and Affiliations

  1. Central Electron Microscopy Laboratory, Northwestern University Medical School, 60611, Chicago, IL, USA

    Jerome J. Trout

  2. Neurology Laboratory, Research Service, VA Lakeside Medical Center, Northwestern University Medical School, 60611, Chicago, IL, USA

    Jerome J. Trout, Chung Y. Lu & Suneet Sahgal

  3. Departments of Neurology, Northwestern University Medical School, 60611, Chicago, IL, USA

    Jerome J. Trout

  4. Departments of Cellular, Molecular and Developmental Biology, Northwestern University Medical School, 60611, Chicago, IL, USA

    A. D. Goldstone

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  1. Jerome J. Trout
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  2. Chung Y. Lu
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  3. A. D. Goldstone
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  4. Suneet Sahgal
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Trout, J.J., Lu, C.Y., Goldstone, A.D. et al. Polyamines and NMDA receptors modulate pericapillary astrocyte swelling following cerebral cryo-injury in the rat. J Neurocytol 24, 341–346 (1995). https://doi.org/10.1007/BF01189061

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  • DOI: https://doi.org/10.1007/BF01189061

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