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Inflammatory Markers in Stroke

  • Chapter
Neuroinflammation

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Stroke and cerebral infarction have long been a major health problem worldwide because they are major causes of disability and intellectual impairment in the elderly. Recently, significant advances have been made in our understanding of the molecular and biochemical mechanisms of ischemia-induced brain damage. During the past decade, a considerable amount of experimental studies have been devoted to elucidating the mechanisms of ischemic neuronal death mediated by excitatory amino acids (EAAs) and calcium (1–3). These studies have shown that cerebral ischemia induces a massive release of EAAs, glutamate and aspartate, which in turn lead to an activation of N-methyl-D-aspartate (NMDA) and nonNMDA subtypes of glutamate receptors and an increase in intracellular calcium concentrations, triggering a chain reaction that leads to ischemia-induced neuronal death. A growing number of promising drugs with powerful cerebroprotective effects have been reported in basic pharmacology using experimental animals in line with this excitotoxic hypothesis (4–7).

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References

  1. 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 

  2. Siesjd, B. K. and Bengtsson, F. (1989) Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J. Cereb. Blood Flow Metab. 9, 127–140.

    Article  Google Scholar 

  3. Choi, D. W. (1990) Cerebral hypoxia: some new approaches and unanswered questions. J. Neurosci. 10, 2493–2501.

    PubMed  CAS  Google Scholar 

  4. Choi, D. W. (1990) Methods for antagonizing glutamate toxicity. Cerebrovasc. Brain Metab. Rev. 2, 105–147.

    PubMed  CAS  Google Scholar 

  5. Meldrum, B. (1990) Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission. Cerebrovasc. Brain Metab. Rev. 2, 27–57.

    PubMed  CAS  Google Scholar 

  6. Hara, H., Kato, H., Sukamoto, T., Tsukamoto, G., and Kogure, K. (1994) Pharmacological prevention of ischemia-induced brain damage. Drugs of Today 30, 123–144.

    CAS  Google Scholar 

  7. Gill, R. (1994) The pharmacology of a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate antagonists and their role in cerebral ischemia. Cerebrovasc. Brain Metab. Rev. 6, 225–256.

    PubMed  CAS  Google Scholar 

  8. Streit, W. J., Graeber, M. B., and Kreutzberg, G. W. (1989) Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system. J. Neuroimmunol. 21, 117–123.

    Article  PubMed  CAS  Google Scholar 

  9. Marty, S., Dusart, I., and Peschanski, M. (1991) Glial changes following an excitotoxic lesion in the CNS. I. microglia/macrophages. Neuroscience 45, 529–539.

    Google Scholar 

  10. Morioka, T., Kalehua, A. N., and Streit, W. J. (1991) The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J. Cereb. Blood Flow Metab. 11, 966–973.

    Article  PubMed  CAS  Google Scholar 

  11. Gehrmann, J., Bonnekoh, P., Miyazawa, T., Hossmann, K.-A., and Kreutzberg, G. W. (1992) Immunocytochemical study of an early microglial activation in ischemia. J. Cereb. Blood Flow Metab. 12, 257–269.

    Article  PubMed  CAS  Google Scholar 

  12. Banati, R. B., Gehrmann, J., Schubert, P., and Kreutzberg G. W. (1993) Cytotoxicity of microglia, Glia 7, 111–118.

    Article  PubMed  CAS  Google Scholar 

  13. Finsen, B. R., Jorgensen, M. B., Diemer, N. H., and Zimmer, J. (1993) Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippo-campus. Glia 7, 41–49.

    Article  PubMed  CAS  Google Scholar 

  14. Jorgensen, M. B., Finsen, B. R., Jensen, M. B., Castellano, B., Diemer, N. H., and Zimmer, J. (1993) Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus. Exp. Neurol. 120, 70–88.

    Article  PubMed  CAS  Google Scholar 

  15. Colton, A. C. and Gilbert, D. L. (1987) Production of superoxide by a CNS macrophage, the microglia. FEBS Lett. 223, 284–288.

    Article  PubMed  CAS  Google Scholar 

  16. Boje, K. M. and Arora, P. K. (1992) Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res. 587, 250–256.

    Article  PubMed  CAS  Google Scholar 

  17. Giulian, D. (1993) Reactive glia as rivals in regulating neuronal survival. Glia 7, 102–110.

    Article  PubMed  CAS  Google Scholar 

  18. Giulian, D. and Vaca, K. (1993) Inflammatory glia mediate delayed neuronal damage after ischemia in the central nervous system. Stroke 24 (Suppl. I) I84–194.

    Google Scholar 

  19. Giulian, D., Vaca, K., and Corpuz, M. (1993) Brain glia release factors with opposing actions upon neuronal survival. J. Neurosci. 13, 29–37.

    PubMed  CAS  Google Scholar 

  20. Akiyama, H., Itagaki, S., and McGeer, P. L. (1988) Major histocompatibility complex antigen expression on rat microglia following epidural kainic acid lesion. J. Neurosci. Res. 20, 147–157.

    Article  PubMed  CAS  Google Scholar 

  21. Morioka, T., Kalehua, A. N., and Streit, W. J. (1992) Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischemia. Acta Neuropathol. 83, 149–157.

    Article  PubMed  CAS  Google Scholar 

  22. Petito, C. K., Morgello, S., Felix, J. C., and Lesser, M. L. (1990) The two patterns of reactive astrocytosis in postischemic rat brain. J. Cereb. Blood Flow Metab. 10, 850–859.

    Article  PubMed  CAS  Google Scholar 

  23. Schmidt-Kastner, R., Szymas, J., and Hosmann, K.-A. (1990) Immunohistochemical study of glial reaction and serum protein extravasation in relation to neuronal damage in rat hippocampus after ischemia. Neuroscience 38, 527–540.

    Article  PubMed  CAS  Google Scholar 

  24. Chen, H., Chopp, M., Schultz, L., Bodzin, G., and Garcia, J. H. (1993) Sequential neuronal and astrocytic changes after transient middle cerebral artery occlusion in the rat. J. Neurol. Sci. 118, 109–116.

    Article  PubMed  CAS  Google Scholar 

  25. Garcia, J. H., Yoshida, Y., Chen, H., Li, Y., Zhang, Z. G., Lian, J., Chen, S., and Chopp, M. (1993) Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am. J. Pathol. 142, 623–635.

    PubMed  CAS  Google Scholar 

  26. Walz, W. (1989) Role of glial cells in the regulation of the brain ion microenvironment. Prog. Neurobiol. 33, 309–333.

    Article  PubMed  CAS  Google Scholar 

  27. Nicholls, D. and Attwell, D. (1990) The release and uptake of excitatory amino acids. Trends Pharmacol. Sci. 11, 462–468.

    Article  PubMed  Google Scholar 

  28. Brightman, M. (1991) Implication of astroglia in the blood-brain barrier. Ann. NY Acad. Sci. 633, 343–347.

    Article  PubMed  CAS  Google Scholar 

  29. Abbott, N. J., Revest, P. A., and Romero, I. A. (1992) Astrocyte-endothelial interaction: physiology and pathology. Neuropathol. Appl. Neurobiol. 18, 424–433.

    Article  PubMed  CAS  Google Scholar 

  30. Kato, H., Kogure, K., Araki, T., and Itoyama, Y. (1994) Astroglial and microglial reactions in the gerbil hippocampus with induced ischemic tolerance. Brain Res. 664, 101–107.

    Article  Google Scholar 

  31. Streit, W. J., Graeber, M. B., and Kreutzberg, G. W. (1988) Functional plasticity of microglia: a review. Glia 1, 301–307.

    Article  PubMed  CAS  Google Scholar 

  32. Graeber, M. B. and Streit, W. J. (1990) Microglia• immune network in the CNS. Brain Pathol. 1, 2–5.

    Article  PubMed  CAS  Google Scholar 

  33. Giulian, D. and Baker, T. J. (1985) Peptide released by ameboid microglia regulate astroglial proliferation. J. Cell. Biol. 101, 2411–2415.

    Article  PubMed  CAS  Google Scholar 

  34. Brierley, J. B. and Brown, A. W. (1982) The origin of lipid phagocytes in the central nervous system: I. The intrinsic microglia. J. Comp. Neurol. 211, 397–406.

    Article  PubMed  CAS  Google Scholar 

  35. Giulian, D. (1987) Ameboid microglia as effectors of inflammation in the central nervous system. J. Neurosci. Res. 18, 155–171.

    Article  PubMed  CAS  Google Scholar 

  36. Banati, R. B. and Graeber, M. B. (1994) Surveillance, intervention and cytotoxicity: Is there a protective role of microglia? Dev. Neurosci. 16, 114–127.

    CAS  Google Scholar 

  37. Kato, H., Kogure, K., Araki, T., and Itoyama, Y. (1995) Graded expression of immunomolecules on activated microglia in the hippocampus following ischemia in a rat model of ischemic tolerance. Brain Res. 694, 85–93.

    Article  PubMed  CAS  Google Scholar 

  38. Streit, W. J. (1990) An improved staining method for rat microglial cells using the lectin from Griffonia simplicifolia (GSA I-B,). J. Histochem. Cytochem. 38, 1683–1686.

    Article  PubMed  CAS  Google Scholar 

  39. Kirino, T. (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 239, 57–69.

    Article  PubMed  CAS  Google Scholar 

  40. Pulsinelli, W. A., Brierly, J. B., and Plum, F. (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann. Neurol. 11, 491–498.

    Article  PubMed  CAS  Google Scholar 

  41. Wieloch, T. (1985) Neuronal correlates to selcetive neuronal vulnerability. Prog. Brain Res. 63, 69–85.

    Article  PubMed  CAS  Google Scholar 

  42. Araki, T., Kato, H., and Kogure, K. (1989) Selective neuronal vulnerability following transient cerebral ischemia in the gerbil: distribution and time course. Acta Neurol. Scand. 80, 548–553.

    Article  PubMed  CAS  Google Scholar 

  43. Kirino, T., Tamura, A., and Sano, K. (1984) Delayed neuronal death in the rat hippocampus following transient forebrain ischemia. Acta Neuropathol. 64, 139–147.

    Article  PubMed  CAS  Google Scholar 

  44. Kitagawa, K., Matsumoto, M., Tagaya, M., Hata, R., Ueda, H., Niinobe, M., Handa, N., Fukunaga, R., Kimura, K., Mikoshiba, K., and Kamata, T. (1990) “Ischemic tolerance” phenomenon found in the brain. Brain Res. 528, 21–24.

    Google Scholar 

  45. Kirino, T., Tsujita, Y., and Tamura, A. (1991) Induced tolerance to ischemia in gerbil hippocampal neurons. J. Cereb. Blood Flow Metab. 11, 299–307.

    Article  PubMed  CAS  Google Scholar 

  46. Kato, H., Liu, Y., Araki, T., and Kogure, K. (1991) Temporal profile of the effects of pretreatment with brief cerebral ischemia on the neuronal damage following secondary ischemic insult in the gerbil: cumulative damage and protective effects. Brain Res. 553, 238–242.

    Article  PubMed  CAS  Google Scholar 

  47. Blinzinger, K. and Kreutzberg, G. W. (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z. Zellforsch. 85, 145–157.

    Article  PubMed  CAS  Google Scholar 

  48. Wieloch, T., Lindvall, O., Blomqvist, P., and Gage, F. H. (1985) Evidence for amelioration of ischaemic neuronal damage in the hippocampal formation by lesions of the perforant path. Neurol. Res. 7, 24–26.

    PubMed  CAS  Google Scholar 

  49. Buchan, A. M. and Pulsinelli, W. A. (1990) Septo-hippocampal deafferentation protects CAl neurons against ischemic injury. Brain Res. 512, 7–14.

    Article  PubMed  CAS  Google Scholar 

  50. Kettenmann, H., Hoppe, D., Gottmann, K., Banati, R., and Kreutzberg, G. W. (1990) Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages. J. Neurosci. Res. 26, 278–287.

    Article  PubMed  CAS  Google Scholar 

  51. Gehrmann, J., Bonnekoh, P., Miyazawa, T., Oschlies, U., Dux, E., Hossmann, K.-A., and Kreutzberg, G. W. (1992) The microglial reaction in the rat hippocampus following global ischemia: immuno-electron microscopy. Acta Neuropathol. 84, 588–595.

    Article  PubMed  CAS  Google Scholar 

  52. Frei, K., Siepl, C., Groscurth, P., Bodmer, S., Schwerdel, C., and Fontana, A. (1987) Antigen presentation and tumor cytotoxicity by interferon-y-treated microglial cells. Eur. J. Immunol. 17, 1271–1278.

    Article  PubMed  CAS  Google Scholar 

  53. Giulian, D. and Ingemann, J. E. (1988) Colony-stimulating factors as promotors of ameboid microglia. J. Neurosci. 8, 4707–4717.

    PubMed  CAS  Google Scholar 

  54. Dickson, D. W., Mattiace, L. A., Kure, K., Hutchins, K., Lyman, W. D., and Brosnan, C. F. (1991) Microglia in human disease, with an emphasis on acquired immune deficiency syndrome. Lab. Invest. 64, 135–156.

    PubMed  CAS  Google Scholar 

  55. Steinger, B. and van der Meide, P. H. (1988) Rat ependyma and microglia cells express class II MHC antigens after intravenous infusion of recombinant gamma interferon. J. Neuroimmunol. 19, 111–118.

    Article  Google Scholar 

  56. Kato, H., Kogure, K., Liu, X.-H., Araki, T., and Itoyama, Y. (1996) Progressive expression of immunomolecules on activated microglia and invading leukocytes following focal cerebral ischemia in the rat. Brain Res. 734, 203–212.

    Article  PubMed  CAS  Google Scholar 

  57. Morioka, T., Kalehua, A. N., and Streit, W. J. (1993) Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. J. Comp. Neurol. 327, 123–132.

    Article  PubMed  CAS  Google Scholar 

  58. Nagasawa, H. and Kogure, K. (1989) Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke 20, 1037–1043.

    Article  PubMed  CAS  Google Scholar 

  59. Kochaneck, P. M. and Hallenbeck, J. M. (1992) Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23, 1367–1379.

    Article  Google Scholar 

  60. Garcia, J. H., Liu, K. F., Yoshida, Y., Lian, J., Chen, S., and del Zoppo, G. L. (1994) Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am. J. Pathol. 144, 188–199.

    PubMed  CAS  Google Scholar 

  61. Matsuo, Y., Onodera, H., Shiga, Y., Nakamura, M., Kihara, T., and Kogure, K. (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effect of neutrophil depletion. Stroke 25, 1469–1475.

    Article  PubMed  CAS  Google Scholar 

  62. Matsuo, Y., Onodera, H., Shiga, Y., Shozuhara, H., Ninomiya, M., Kihara, T., Tamatani, T., Miyasaka, M., and Kogure, K. (1994) Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat. Brain Res. 656, 344–352.

    Article  PubMed  CAS  Google Scholar 

  63. Yamasaki, Y., Matsuo, Y., Matsuura, N., Onodera, H., Itoyama, Y., and Kogure, K. (1995) Transient increase of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in ischemic brain areas after focal ischemia in rats. Stroke 26, 318–323.

    Article  PubMed  CAS  Google Scholar 

  64. Yamasaki, Y., Matsuura, N., Shozuhara, H., Onodera, H., Itoyama, Y., and Kogure, K. (1995) Interleukin-1 as a pathogenic mediator of ischemic brain damage in rats. Stroke 26, 676–681.

    Article  PubMed  CAS  Google Scholar 

  65. Springer, T. A. (1990) Adhesion receptors of the immune system. Nature 346, 425–434.

    Article  PubMed  CAS  Google Scholar 

  66. Okada, Y., Copeland, B. R., Mori, E., Tung, M.-M., Thomas, W. S., and del Zoppo, G. J. (1994) P-Secletin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion. Stroke 25, 202–211.

    Article  PubMed  CAS  Google Scholar 

  67. Dutka, A. J., Kochanek, P. M., and Hallenbeck, J. M. (1989) Influence of granulocytopenia on canine cerebral ischemia induced by air embolism. Stroke 20, 390–395.

    Article  PubMed  CAS  Google Scholar 

  68. Vasthare, V. S., Heinel, L. A., Rosenwasser, R. H., and Tuma, R. F. (1990) Leukocyte involvement in cerebral ischemia and reperfusion injury. Surg. Neurol. 33, 261–265.

    Article  PubMed  CAS  Google Scholar 

  69. Clark, W. M., Madden, K. P., Rothlein, R., and Zivin, J. A. (1991) Reduction of central nervous system ischemic injury in rabbits using leukocyte adhesion antibody treatment. Stroke 22, 877–883.

    Article  PubMed  CAS  Google Scholar 

  70. Chen, H., Chopp, M., and Bodzin, G. (1992) Neutropenia reduces the volume of cerebral infarct after transient middle cerebral artery occlusion in the rat. Neurosci. Res. Commun. 11, 93–99.

    Google Scholar 

  71. Mori, E., del Zoppo, G. L., Chambers, D., Copeland, B. R., and Arfors, K. E. (1992) Inhibition of polymorphonuclear leukocyte adherence suppresses no-reflow after focal cerebral ischemia in baboons. Stroke 23, 712–718.

    Article  PubMed  CAS  Google Scholar 

  72. Bowes, M. P., Zivin, J. A., and Rothlein, R. (1993) Monoclonal antibody to ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. Exp. Neurol. 119, 215–219.

    Article  PubMed  CAS  Google Scholar 

  73. Chopp, M., Zhang, R. L., Chen, H., Li, Y., Jiang, N., and Rusche, J. R. (1994) Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke 25, 869–876.

    Article  PubMed  CAS  Google Scholar 

  74. Iadecola, C., Zhang, F., Xu, S., Casey, R., and Ross, E. (1995) Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J. Cereb. Blood Flow Metab. 15, 378–384.

    Article  PubMed  CAS  Google Scholar 

  75. Giulian, D., Chen, J., Ingeman, J. E., George, J. K., and Noponen, M. (1989) The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J. Neurosci. 9, 4416–4429.

    PubMed  CAS  Google Scholar 

  76. Giulian, D. and Robertson, C. (1990) Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann. Neurol. 27, 33–42.

    Article  PubMed  CAS  Google Scholar 

  77. Nagata, K., Takei, N., Nakajima, K., Saito, H., and Kohsaka, S. (1993) Microglial conditioned medium promotes survival and development of cultured mesencephalic neurons from embryonic rat brain. J. Neurosci. Res. 34, 357–363.

    Article  PubMed  CAS  Google Scholar 

  78. Lehrmann, E., Kiefer, R., Finsen, B., Diemer, N. H., Zimmer, J., and Hartung, H.-P. (1995) Cytokines in cerebral ischemia: expression of transforming growth factor beta-1 (TGF-ßl) mRNA in the postischemic adult rat hippocampus. Exp. Neurol. 131, 114–123.

    Article  PubMed  CAS  Google Scholar 

  79. Lees, G. L. (1993) The possible contribution of microglia and macrophages to delayed neuronal death after ischemia. J. Neurol. Sci. 114, 119–122.

    Article  PubMed  CAS  Google Scholar 

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  1. Hiroyuki Kato
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  1. Pharmacology, CoCensys, Inc., Irvine, CA, USA

    Paul L. Wood (Director) (Director)

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Kato, H. (1998). Inflammatory Markers in Stroke. In: Wood, P.L. (eds) Neuroinflammation. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-473-3_3

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  • DOI: https://doi.org/10.1007/978-1-59259-473-3_3

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