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. 1999 Feb;19(1):93–108. doi: 10.1023/A:1006920725663

Biochemical and Molecular Characteristics of the Brain with Developing Cerebral Infarction

Hiroyuki Kato 1, Kyuya Kogure 2
PMCID: PMC11545405  PMID: 10079969

Abstract

1. We review the biochemical and molecular changes in brain with developing cerebral infarction, based on recent findings in experimental focal cerebral ischemia.

2. Occlusion of a cerebral artery produces focal ischemia with a gradual decline of blood flow, differentiating a severely ischemic core where infarct develops rapidly and an area peripheral to the core where the blood flow reduction is moderate (called penumbra). Neuronal injury in the penumbra is essentially reversible but only for several hours. The penumbra area tolerates a longer duration of ischemia than the core and may be salvageable by pharmacological agents such as glutamate antagonists or prompt reperfusion.

3. Upon reperfusion, brain cells alter their genomic properties so that protein synthesis becomes restricted to a small number of proteins such as stress proteins. Induction of the stress response is considered to be a rescue program to help to mitigate neuronal injury and to endow the cells with resistance to subsequent ischemic stress. The challenge now is to determine how the neuroprotection conferred by prior sublethal ischemia is achieved so that rational strategies can be developed to detect and manipulate gene expression in brain cells vulnerable to ischemia.

4. Expansion of infarction may be caused by an apoptotic mechanism. Investigation of apoptosis may also help in designing novel molecular strategies to prevent ischemic cell death.

5. Ischemia/reperfusion injury is accompanied by inflammatory reactions induced by neutrophils and monocytes/macrophages infiltrated and accumulated in ischemic areas. When the role of the inflammatory/immune systems in ischemic brain injury is revealed, new therapeutic targets and agents will emerge to complement and synergize with pharmacological intervention directed against glutamate and Ca2+ neurotoxicity.

Keywords: focal cerebral ischemia, cerebral infarction, penumbra, gene expression, stress response, inflammatory reaction

REFERENCES

  1. Abbott, N. J., Revest, P. A., and Romero, I. A. (1992). Astrocyte-endothelial interaction: Physiology and pathology. Neuropathol. Appl. Neurobiol.18:424–433. [DOI] [PubMed] [Google Scholar]
  2. Abe, K., Tanzi, R. E., and Kogure, K. (1991). Selective induction of Kunitz-type protein inhibitor domain-containing amyloid precursor protein mRNA after persistant focal ischemia in rat cerebral cortex. Neurosci. Lett.125:172–174. [DOI] [PubMed] [Google Scholar]
  3. An, G., Lin, T. N., Liu, J. S., Xue, J. J., He, Y. Y., and Hsu, C. Y. (1993). Expression of c-fos and c-jun family genes after focal cerebral ischemia. Ann. Neurol.33:457–464. [DOI] [PubMed] [Google Scholar]
  4. Araki, T., Kato, H., Inoue, T., and Kogure, K. (1990). Impairment of protein synthesis following brief cerebral ischemia in the gerbil. Acta Neuropathol.79:501–505. [DOI] [PubMed] [Google Scholar]
  5. Astrup, J., Siesjö, B. K., and Symon, L. (1981). Thresholds in cerebral ischemia—The ischemic penumbra. Stroke12:723–725. [DOI] [PubMed] [Google Scholar]
  6. Beckmann, R. P., Mizzen, L. A., and Welch, W. J. (1990). Interaction of HSP70 with newly synthesized proteins: Implications for protein folding and assembly. Science248:850–854. [DOI] [PubMed] [Google Scholar]
  7. Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N. H. (1984). Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J.Neurochem.43:1369–1374. [DOI] [PubMed] [Google Scholar]
  8. Blinzinger, K., and Kreutzberg, G. W. (1968). Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z. Zellforsch.85:145–157. [DOI] [PubMed] [Google Scholar]
  9. 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. [DOI] [PubMed] [Google Scholar]
  10. Brightman, M. (1991). Implication of astroglia in the blood-brain barrier. Ann. N.Y. Acad. Sci.633:343–347. [DOI] [PubMed] [Google Scholar]
  11. Buchan, A. M., Xue, D., Huang, Z.-G., Smith, K. H., and Lesiuk, H. (1991). Delayed AMPA receptor blockade reduces cerebral infarction induced by focal ischemia. NeuroReport2:473–476. [DOI] [PubMed] [Google Scholar]
  12. Buchan, A. M., Slivka, A., and Yue, D. (1992). The effect of the NMDA receptor antagonist MK-801 on cerebral blood flow and infarct volume in experimental focal stroke. Brain Res.574:171–177. [DOI] [PubMed] [Google Scholar]
  13. 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. Comm.11:93–99. [Google Scholar]
  14. 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. [DOI] [PubMed] [Google Scholar]
  15. Chen, J., Graham, S. H., Chan, P. H., Lan, J., Zhou, R. L., and Simon, R. P. (1995). Bcl-2 is expressed in neurons that survive focal ischemia in the rat. NeuroReport6:394–398. [DOI] [PubMed] [Google Scholar]
  16. Choi, D. W. (1990a). Cerebral hypoxia: some new approaches and unanswered questions. J. Neurosci.10:2493–2501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Choi, D. W. (1990b). Methods for antagonizing glutamate toxicity. Cerebrovasc. Brain Metab. Rev.2:105–147. [PubMed] [Google Scholar]
  18. Chopp, M., Chen, H., Ho, K.-L., Dereski, M. O., Brown, E., Hetzel, F. W., and Welch, K. M. (1989). Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat. Neurology39:1396–1398. [DOI] [PubMed] [Google Scholar]
  19. 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. Stroke25:869–876. [DOI] [PubMed] [Google Scholar]
  20. 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. Stroke22:877–883. [DOI] [PubMed] [Google Scholar]
  21. Dietrich, W. D. (1992). The importance of brain temperature in cerebral injury. J. Neurotrauma9(Suppl. 2):S475-S485. [PubMed] [Google Scholar]
  22. Dutka, A. J., Kochanek, P. M., and Hallenbeck, J. M. (1989). Influence of granulo-cytopenia on canine cerebral ischemia induced by air embolism. Stroke20:390–395. [DOI] [PubMed] [Google Scholar]
  23. Eddleston, E., and Mucke, L. (1993). Molecular profile of reactive astrocytes. Implications for their role in neurologic disease. Neuroscience54:15–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gass, P., Spranger, M., Herdegen, T., Bravo, R., Köck, P., Hacke, W., and Kiessling, M. (1992). Induction of fos and jun proteins after focal ischemia in the rat: Different effect of the N-methyl-D-aspartate receptor antagonist MK-801. Acta Neuropathol.84:545–553. [DOI] [PubMed] [Google Scholar]
  25. Gill, R., Andiné, P., Hillered, L., Persson, L., and Hagberg, H. (1992a). The effect of MK-801 on cortical spreading depression in the penumbral zone following focal ischaemia in the rat. J. Cereb. Blood Flow Metab.12:371–379. [DOI] [PubMed] [Google Scholar]
  26. Gill, R., Nordholm, L., and Lodge, D. (1992b). The neuroprotective actions of 2,3-dihydroxy-6-nitro-7-sulhamoyl-benzo(F) quinoxaline (NBQX) in a rat focal ischemia model. Brain Res.580:35–43. [DOI] [PubMed] [Google Scholar]
  27. Giulian, D. (1993). Reactive glia as rivals in regulating neuronal survival. Glia7:102–110. [DOI] [PubMed] [Google Scholar]
  28. Giulian, D., and Robertson, C. (1990). Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann. Neurol.27:33–42. [DOI] [PubMed] [Google Scholar]
  29. Giulian, D., Vaca, K., and Corpuz, M. (1993). Brain glia release factors with opposing actions upon neuronal survival. J. Neurosci.13:29–37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Heiss, W.-D., and Rosner G. (1983). Functional recovery of cortical neurons as related to degree and duration of ischemia. Ann. Neurol.14:294–301. [DOI] [PubMed] [Google Scholar]
  31. Hossmann, K.-A. (1976). Development and resolution of ischemic brain swelling. In Papius, H. M., and Feindel, W. (eds.), Dynamics of Brain Edema, Springer-Verlag, Berlin, pp. 219–227. [Google Scholar]
  32. Hossmann, K.-A. (1994). Viability thresholds and the penumbra of focal ischemia. Ann. Neurol.36:557–565. [DOI] [PubMed] [Google Scholar]
  33. 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. [DOI] [PubMed] [Google Scholar]
  34. Jacewicz, M., Kiessling, M., and Pulsinelli, W. A. (1986). Selective gene expression in focal cerebral ischemia. J. Cereb. Blood Flow Metab.6:263–272. [DOI] [PubMed] [Google Scholar]
  35. 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. [DOI] [PubMed] [Google Scholar]
  36. 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. [DOI] [PubMed] [Google Scholar]
  37. Kato, H., Kogure, K., Liu, X.-H., Araki T., Kato, K., and Itoyama, Y. (1995). Immuno-histochemical localization of the low molecular weight stress protein HSP27 following focal cerebral ischemia in the rat. Brain Res.679:1–7. [DOI] [PubMed] [Google Scholar]
  38. Kerr, J. F. R., Wyllie, A. H., and Currie, A. R. (1972). Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer26:239–245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kiessling, M., Dienel, M., Jacewicz, M., and Pulsinelli, W. A. (1986). Protein synthesis in postischemic rat brain: A two-dimensional electrophoretic analysis. J. Cereb. Blood Flow Metab.6:642–649. [DOI] [PubMed] [Google Scholar]
  40. Kinouchi, H., Sharp, F. R., Hill, M. P., Koistinaho, J., Sagar, S. M., and Chan, P. H. (1993). Induction of 70-kDa heat shock protein and hsp70 mRNA following transient focal cerebral ischemia in the rat. J. Cereb. Blood Flow Metab.13:105–115. [DOI] [PubMed] [Google Scholar]
  41. Kinouchi, H., Sharp, F. R., Chan, P. H., Koistinaho, J., Sagar, S. M., and Yoshimoto, T. (1994). Induction of c-fos, junB, c-jun, and hsp70mRNA in cortex, thalamus, basal ganglia, and hippocampus following miffle cerebral artery occlusion. J. Cereb. Blood Flow Metab.14:808–817. [DOI] [PubMed] [Google Scholar]
  42. Kirino, T. (1982). Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res.239:57–69. [DOI] [PubMed] [Google Scholar]
  43. Kirino, T., Tsujita, Y., and Tamura, A. (1991). Induced tolerance to ischemia in gerbil hippocampal neurons. J. Cereb. Blood Flow Metab.11:299–307. [DOI] [PubMed] [Google Scholar]
  44. Kitagawa, K., Matsumoto, M., Tagaya, M., Hata, R., Ueda, H., Niinobe, M., Handa, N., Fukunaga, R., Kimura, K., Mikoshiba, K., and Kamada, T. (1990). “Ischemic tolerance” phenomenon found in the brain. Brain Res.528:21–24. [DOI] [PubMed] [Google Scholar]
  45. Kochaneck, P. M., and Hallenbeck, J. M. (1992). Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke23:1367–1379. [DOI] [PubMed] [Google Scholar]
  46. Kogure, K., Tanaka, T., and Araki, T. (1988). The mechanism of ischemia-induced brain cell injury: The membrane theory. Neurochem. Pathol.9:145–170. [DOI] [PubMed] [Google Scholar]
  47. Koizumi, J., Yoshida, Y., Nakazawa, T., and Ooneda, G. (1986). Experimental studies of ischemic brain edema. 1. A new experimental model of cerebral ischemia in rats in which recirculation can be introduced in the ischemic area. Jpn. J. Stroke8:1–8. [Google Scholar]
  48. Kraig, R. P., and Nicholson, C. (1978). Extracellular ionic variations during spreading depression. Neuroscience3:1045–1059. [DOI] [PubMed] [Google Scholar]
  49. Kumon, Y., Sakaki, S., Kadota, O., Matsuda, S., Fujita, H., Yoshimura, H., and Sakanaka, M. (1993). Transient increase in endogenous basic fibroblast growth factor in neurons of ischemic rat brains. Brain Res.605:169–174. [DOI] [PubMed] [Google Scholar]
  50. Landry, J., and Chretine, P. (1989). Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells. J. Cell Biol.109:7–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Li, Y., Chopp, M., Garcia, J. H., Yoshida, Y., Zhang, Z. G., and Levine, S. R. (1992). Distribution of the 72-kDa heat-shock protein as a function of transient focal cerebral ischemia in rats. Stroke23:1292–1298. [DOI] [PubMed] [Google Scholar]
  52. Li, Y., Chopp, M., Zhang, Z. G., Zhang, R. L., and Garcia, H. (1993). Neuronal survival is associate with 72-kDa heat shock protein expression after transient middle cerebral artery occlusion in the rat. J. Neurol. Sci.120:187–194. [DOI] [PubMed] [Google Scholar]
  53. Li, Y., Chopp, M., Zhang, Z. G., Zaloga, C., Niewenhuis, L., and Gautam, S. (1994). p53-immunoreactive protein and p53 mRNA expression after transient middle cerebral artery occlusion in rats. Stroke25:849–856. [DOI] [PubMed] [Google Scholar]
  54. Li, Y., Chopp, M., Jiang, N., Yao, F., and Zaloga, C. (1995). Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J. Cereb. Blood Flow Metab.15:389–397. [DOI] [PubMed] [Google Scholar]
  55. Lindquist, S., and Craig, E. A. (1988). The heat-shock protein. Annu. Rev. Genet.22:631–677. [DOI] [PubMed] [Google Scholar]
  56. Lindvall, O., Ernfors, P., Bengzon, J., Kokaia, Z., Smith, M. L., Siesjö, B. K., and Persson, H. (1992). Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophic 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma. Proc. Natl. Acad. Sci. USA89:648–652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Linnik, M. D., Zobrist, R. H., and Hatfield, M. D. (1993). Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke24:2002–2009. [DOI] [PubMed] [Google Scholar]
  58. Liu, T., McDonnell, P. C., Young, P. R., White, R. F., Siren, A. L., Hallenbeck, J. M., Barone, F. C., and Feuerstein, G. Z. (1993). Interleukin-1b mRNA expression in ischemic rat cortex. Stroke24:1746–1751. [DOI] [PubMed] [Google Scholar]
  59. Liu, T., Clark, R. K., McDonnell, P. C., Young, P. R., White, R. F., Barone, F. C., and Feuerstein, G. Z. (1994). Tumor necrosis factor-a expression in ischemic neurons. Stroke25:1481–1488. [DOI] [PubMed] [Google Scholar]
  60. Longa, E. Z., Weinstein, P. R., Carlson, S., and Cummins, R. (1989). Reversible middle cerebral artery occlusion without craniotomyin rats. Stroke20:84–91. [DOI] [PubMed] [Google Scholar]
  61. Matsumoto, K., Graf, R., Rosner, G., Taguchi, J., and Heiss, W.-D. (1993). Elevation of neuroactive substances in the cortex of cats during prolonged focal ischemia. J. Cereb. Blood Flow Metab.13:586–594. [DOI] [PubMed] [Google Scholar]
  62. Matsuo, Y., Onodera, H., Shiga, Y., Shozuhara, H., Ninomiya, M., Kihara, T., Tamatani, T., Miyasaka, M., and Kogure, K. (1994). Roll of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat. Brain Res.656:344–352. [DOI] [PubMed] [Google Scholar]
  63. Memezawa, H., Smith, M.-L., and Siesjö, B. K. (1992). Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats. Stroke23:552–559. [DOI] [PubMed] [Google Scholar]
  64. Mies, G., Ishimaru, S., Xie, Y., Seo, K., and Hossmann, K.-A. (1991). Ischemic threshold of brain protein synthesis after unilateral carotid artery occlusion in gerbils. J. Cereb. Blood Flow Metab.11:753–761. [DOI] [PubMed] [Google Scholar]
  65. Mitani, A., Yanase, H., Sakai, K., Wake, Y., and Kataoka, K. (1993). Origin of intracellular Ca2+ elevation induced by in vitro ischemia-like condition in hippocampal slices. Brain Res.601:103–110. [DOI] [PubMed] [Google Scholar]
  66. Mitani, A., Andou, Y., Matsuda, S., Arai, T., Sakanaka, M., and Kataoka, K. (1994). Origin of ischemia-induced glutamine efflux in the CA1 field of the gerbil hippocampus: An in vivo brain microdialysis study. J. Neurochem.63:2152–2164. [DOI] [PubMed] [Google Scholar]
  67. Morgan, J. I., and Curran, T. (1991). Stimulus-transcription coupling in the nervous system: Involvement of the inducible proto-oncogenes fos and jun. Annu. Rev. Neurosci.14:421–251. [DOI] [PubMed] [Google Scholar]
  68. 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. Stroke23:712–718. [DOI] [PubMed] [Google Scholar]
  69. 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. [DOI] [PubMed] [Google Scholar]
  70. Nagasawa, H., and Kogure, K. (1989). Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke20:1037–1043. [DOI] [PubMed] [Google Scholar]
  71. Nicholls, D., and Attwell, D. (1990). The release and uptake of excitatory amino acids. Trends Pharmacol. Sci.11:462–468. [DOI] [PubMed] [Google Scholar]
  72. Nowak, T. S., Jr. (1985). Synthesis of a stress protein following transient ischemia in the gerbil. J. Neurochem.45:1635–1641. [DOI] [PubMed] [Google Scholar]
  73. 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. Stroke25:202–211. [DOI] [PubMed] [Google Scholar]
  74. Pelham, H. R. B. (1986). Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell46:959–961. [DOI] [PubMed] [Google Scholar]
  75. Petito, C. K., Chung, M. C., Verkhovsky, L. M., and Coopwe, A. J. L. (1992). Brain glutamine synthetase increases following cerebral ischemia in the rat. Brain Res.569:275–280. [DOI] [PubMed] [Google Scholar]
  76. Pulsinelli, W. A., and Duffy, T. E. (1983). Regional energy balance in rat brain after transient forebrain ischemia. J. Neurochem.40:1500–1503. [DOI] [PubMed] [Google Scholar]
  77. Riabowel, K. T., Mizzen, L. A., and Welch, W. J. (1988). Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. Science242:433–436. [DOI] [PubMed] [Google Scholar]
  78. Rothman, S. M., and Olney, J. W. (1986). Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann. Neurol.19:105–111. [DOI] [PubMed] [Google Scholar]
  79. Sauter, A., and Rudin, M. (1990). Calcium antagonists for reduction of brain damage in stroke. J. Cardiovasc. Pharmacol.15(Suppl. 1):S43-S47. [PubMed] [Google Scholar]
  80. Searle, J., Kerr, J. F. K., and Bishop, C. J. (1982). Necrosis and apoptosis: Distinct modes of cell death with fundamentally different significance. Pathol. Annu.17:229–259. [PubMed] [Google Scholar]
  81. Sheng, M., and Greenberg, M. E. (1990). The regulation and function of c-fos and other immediate genes in the nervous system. Neuron4:477–485. [DOI] [PubMed] [Google Scholar]
  82. Siesjö, 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. [DOI] [PubMed] [Google Scholar]
  83. Streit, W. J., Graeber, M. B., and Kreutzberg, G. W. (1988). Functional plasticity of microglia: A review. Glia1:301–307. [DOI] [PubMed] [Google Scholar]
  84. Symon, L., Branston, N. M., Strong, A. J., and Hope, T. D. (1977). The concepts of thresholds of Ischaemia in relation to brain structure and function. J. Clin. Pathol. 30, Suppl. (Roy. Coll. Path.) 11:149–154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Takeda, A., Onodera, H., Sugimoto, A., Kogure, K., Obinata, M., and Shibahara, S. (1993). Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia. Neuroscience55:23–31. [DOI] [PubMed] [Google Scholar]
  86. Tamura, A., Graham, D. I., McCulloch, J., and Teasdale, G. M. (1981). Focal cerebral ischemia in the rat. 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J. Cereb. Blood Flow Metab.1:53–69. [DOI] [PubMed] [Google Scholar]
  87. Thilmann, R., Xie, Y., Klehues, P., and Kiessling, M. (1986). Persistent inhibition of protein synthesis precedes delayed neuronal death in postischemic gerbil hippocampus. Acta Neuropathol.71:88–91. [DOI] [PubMed] [Google Scholar]
  88. Tominaga, T., Kure, S., Narisawa, K., and Yoshimoto, T. (1993). Endonuclease activation following focal ischemic injury in the rat brain. Brain Res.608:21–26. [DOI] [PubMed] [Google Scholar]
  89. Uemura, Y., Kowall, N. W., and Moskowitz, M. A. (1991). Focal ischemia in rat causes time-dependent expression of c-fos protein immunoreactivity in widespread region of ipsilateral cortex. Brain Res.552:99–105. [DOI] [PubMed] [Google Scholar]
  90. Vasthare, V. S., Heinel, L. A., Rosenwasser, R. H., and Tuma, R. F. (1990). Leokocyte involvement in cerebral ischemia and reperfusion injury. Surg. Neurol.33:261–265. [DOI] [PubMed] [Google Scholar]
  91. Walz, W. (1989). Role of glial cells in the regulation of the brain microenvironment. Prog. Neurobiol.33:309–333. [DOI] [PubMed] [Google Scholar]
  92. Wieloch, T. (1985). Neurochemical correlates to selective neuronal vulnerability. Prog. Brain Res.63:69–85. [DOI] [PubMed] [Google Scholar]

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