Skip to main content
SpringerLink
Log in

Stroke

Prevalence and Mechanisms of Cell Death

  • Chapter
Clinical Pharmacology of Cerebral Ischemia

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

Abstract

Cerebrovascular accident (CVA) is a clinical definition used to describe symptoms of an acute neurological disorder caused by disturbance of the cerebral blood supply. Intracerebral and subarachnoid hemorrhages account for approx 20% of CVAs and 80% are of the ischemic type. Stroke defines all conditions in which the duration of the CVA symptoms exceed 24 h. Ischemic CVAs exhibiting short duration of neurologic dysfunction usually not exceeding 10–15 min are transient ischemic attacks (TIAs). A TIA may be a warning sign of an impending stroke. Adequate supply of oxygen and glucose are necessary for the proper functioning of the brain. Minor changes in the cerebral oxygen and glucose supply may invoke damage that is irreversible because the brain has very limited repair capabilities. The most important disadvantage to neural repair is the inability of the neurons to divide. This implies that all neuronal loss caused by CVA is irreversible and that it permanently affects the functioning of the brain. Prevention of a first stroke or recurrent strokes through reduction of known risk factors is the most effective strategy for controlling this devastating disease, but for the near future, such total elimination of stroke is unlikely. Therefore, treatment strategies to limit ischemic brain injury must be identified and developed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Pulsinelli, W., The ischemic penumbra in stroke. Sci. Am. Sci. Med., 2 (1995) 16–25.

    CAS  Google Scholar 

  2. Ricci, S., Celani, M. G., Guercini, G., Rucireta, P., Vitali, R., La Rosa, F., Duca, E., Ferraguzzi, R., Paolotti, M., and Seppolini, D., First-year results of a community-based study of stroke incidence in Umbria, Italy, Stroke, 20 (1989) 853–857.

    Google Scholar 

  3. Ricci, S., Celani, M. G., La Rosa, F., Vitali, R., Duca, E., Ferraguzi, R., Paolotti, M., Seppolini, D., Caputo, N., and Chiurulla, C., SEPIVAC: a community based study of stroke incidence in Umbria, Italy, J. Neurol. Neurosurg. Psychiatry, 54 (1991) 695–698.

    PubMed  CAS  Google Scholar 

  4. Ricci, S., Celani, M. G., La Rosa, F., Vitali, R., Duca, E., Ferraguzi, R., Paolotti, M., Seppolini, D., Caputo, N., and Chiurulla, C., A community-based study of incidence and risk factors and outcome of transient ischaemic attacks in Umbria, Italy, J. Neurol., 238 (1991) 87–90.

    Google Scholar 

  5. Bergman, L., Van der Meulen, J. H. P., Limburg, M., and Habbema, J. D. F., Costs of medical care after first-ever stroke in the Netherlands, Stroke, 26 (1995) 1830–1836.

    Google Scholar 

  6. Knollema, S., Knigge, M. F., Jansen, H. M. L., Ter Horst, G. J., Korf, J., Minderhoud, J. M., and Meyboom-De Jong, B., Het cerebrovasculair accident in de praktijk, Patient Care, 22 (1995) 21–32.

    Google Scholar 

  7. Anderson, C. S. Jamrozik, K. D., Burvill, P. W., Chakera, T. M., Jonhson, G. A., and Stewart-Wynne, E. G., Ascertaining the true incidence of stroke: experience from the Perth community stroke study, Med. J. Aust., 158 (1993) 80–84.

    Google Scholar 

  8. Scott, W. G. and Scott, H., Ischaemic stroke in New Zealand: an economy study, N. Z. Med. J. 107 (1994) 443–446.

    PubMed  CAS  Google Scholar 

  9. Itoh, T., Matsumoto, M., Handa, N., Maeda, H., Hougaku, H., Tsukamoto, Y., Kondo, H., Tanouchi, J., and Kamada, T., Paradoxial embolism as a cause of ischemic stroke of uncertain etiology. A transcranial Doppler sonographic study, Stroke, 25 (1994) 771–775.

    PubMed  CAS  Google Scholar 

  10. Corelei, A., Marini, C., Ferranti, E., Frontini, M., Prencipe, M., and Fieschi, C., A prospective study of cerebral ischemia in the young. Analysis of pathogenic determinants, Stroke, 24 (1993) 362–367.

    Google Scholar 

  11. Futrell, N. and Millikan, C., Frequency, etiology, and prevention of stroke in patients with systemic lupus erythematosus, Stroke, 20 (1989) 583–591.

    PubMed  CAS  Google Scholar 

  12. Herrschaft, H., Heart diseases as a cause of cerebral symptoms and syndromes, Fortschr. Neurol. Psychiatr., 58 (1990) 287–300.

    PubMed  CAS  Google Scholar 

  13. Grau, A. J., Buggle, F., Heindl, S., Steichen-Wiehn, C., Banerjee, T., Maiwald, M., Rohlfs, M., Suhr, H., Fiehn, W., Becher, H., and Hacke, W., Recent infection as a risk factor for cerebrovascular ischemia, Stroke, 26 (1995) 373–379.

    PubMed  CAS  Google Scholar 

  14. Grau, A. J., Buggle, F., Steichen-Wiehn, C., Heindl, S., Banerjee, T., Seitz, R., Winter, R., Forsting, M., Werle, E., Bode, C., Nawroth, P. P., Becher, H., and Hacke, W., Clinical and biochemical analysis in infection-associated stroke, Stroke, 26 (1995) 1520–1526.

    PubMed  CAS  Google Scholar 

  15. Lindenstrom, E., Boysen, G., and Nyboe, J., Risk factors for stroke in Copenhagen, Den- mark. I. Basic demographic and social factors, Neuroepidemiology, 12 (1993) 37–42.

    PubMed  CAS  Google Scholar 

  16. Laloux, P., Ossemann, M., and Jamart, J., Stroke subtypes and risk factors associated with silent infarctions in patients with first-ever stroke or transient ischemic attack, Acta Neurol. Belg., 94 (1994) 17–23.

    PubMed  CAS  Google Scholar 

  17. Kane-Carlsen, P. A., Transient ischemic attacks: clinical features, pathophysiology and management, Nurse Pract.,15 (1990) 9–14.

    Google Scholar 

  18. Lyrer, P., Prognosis of and basis for decision making in transient ichemic attacks, Schweiz. Med. Wochenschr., 125 (1995) 1299–1306.

    PubMed  CAS  Google Scholar 

  19. Rouhart, F., Zagnoli, F., Goas, J. Y., and Mocquard, Y., Cerebral ischemic arterial accidents in young adults, Rev. Neurol. (Paris), 149 (1993) 547–553.

    CAS  Google Scholar 

  20. Ebrahim, S., Clinical Epidemiology of Stroke, Oxford University Press, Oxford, 1990.

    Google Scholar 

  21. MacMahon, S., Peto, R., Cutler, J., Collins, R., Sorlie, P., Neaton, J., Abbott, R., Godwin, J., Dyer, A., and Stamler, J., Blood pressure, stroke, and coronary heart disease, Lancet, 335 (1990) 765–774.

    PubMed  CAS  Google Scholar 

  22. Stamler, J., Dietary salt and blood pressure. Nutrition and cardiocerebrovascular diseases, Ann. NYAcad. Sci., 676 (1993) 122–156.

    Google Scholar 

  23. Post, D. and Smit, P. Th., Sociaal geneeskundige aspecten van het CVA, Patient Care, 22 (1995) 51–55.

    Google Scholar 

  24. Lai, S. M., Alter, M., Friday, G., Sobel, E., Gil-Peralta, A., McCoy, R. L., Levitt, L. P., and Isack, T., Transient ischemic attacks: their frequency in the Leigh Valley, Neuro-epidemiology, 9 (1990) 124–130.

    CAS  Google Scholar 

  25. Whisnant, J. P., Melton, L. J., Dvis, P. H., O’Fallon, W. M., Nishimura, K. and Schoenberg, B. S., Comparisons of case ascertainment by medical record linkage in a cohort follow-up to determine incidence rates for transient ischemic attacks and stroke, J. Clin. Epidemiol., 43 (1990) 791–797.

    PubMed  CAS  Google Scholar 

  26. Ueda, K., Kyohara, Y., and Hasua,Y., Transient ischemic attacks in a Japanese community, Stroke, 18 (1987) 844–847.

    Google Scholar 

  27. Van der Werf, Y. D., De Jongste, M. J. L., and Ter Horst, G. J., The immune system mediates blood-brain barrier damage: possible implications for pathophysiology of neuropsychiatric illnesses, Acta Neuropsychiat., 7 (1995) 114–121.

    Google Scholar 

  28. Barron, S. A., Rogovski, Z., and Hemli, J., Autonomic consequences of cerebral hemisphere infarction, Stroke, 25 (1994) 113–116.

    PubMed  CAS  Google Scholar 

  29. Yamamoto, Y., Akiguchi, I., Oiwa, K., Satoi, H., and Kimura, J., Diminished nocturnal blood pressure decline and lesion site in cerebrovascular disease, Stroke, 26 (1995) 829–833.

    PubMed  CAS  Google Scholar 

  30. Naver, H., Blomstrand, C., Ekholm, S., Jensen, C., Karlsson, T., and Wallin, B. G., Autonomic and thermal sensory symptoms and dysfunction after stroke, Stroke, 26 (1995) 1379–1385.

    PubMed  CAS  Google Scholar 

  31. Demeurisse, G., Verhas, M., and Capon, A., Remote cortical dysfunction in aphasic stroke patients, Stroke, 22 (1991) 1015–1020.

    PubMed  CAS  Google Scholar 

  32. Evans, J. G., Transient neurological dysfunction and risk of stroke in an elderly English population: the different significance of vertigo and non-rotatory dizziness., Age. Ageing, 19 (1990) 43–49.

    PubMed  CAS  Google Scholar 

  33. Lane, R. D., Wallace, J. D., Petrosky, P. P., Schwartz, G. E., and Gradham, A. H., Supraventricular tachycardia in patients with right hemisphere strokes, Stroke, 23 (1992) 362–366.

    PubMed  CAS  Google Scholar 

  34. Ter Horst, G. J., Van den Brink, A., Homminga, S. A., Hautvast, R. W. M., Rakhorst, G., Mettenleiter, T. C., De Jongste, M. J. L., Lie, K. I., and Korf, J., Transneuronal viral labelling of rat heart left ventricle controlling pathways, NeuroReport, 4 (1993) 1307–1311.

    Google Scholar 

  35. Standish, A., Enquist, L. W., and Schwaber, J., S., Innervation of the heart and its central medullary origin defined by viral tracing, Science, 263 (1994) 232–234.

    PubMed  CAS  Google Scholar 

  36. Ter Horst, G. J., Hautvast, R. W. M., De Jongste, M. J. L., and Korf, J., Neuroanatomy of cardiac activity regulating circuitry; a transneuronal retrograde viral tracing study in the rat, Eur. J. Neuroscience, 8 (1996) 101–113.

    Google Scholar 

  37. Oppenheimer, S. M., Gelb, A., Girvin, J. P., and Hachinski, V. C., Cardiovascular effects of human insular cortex stimulation, Neurology, 42 (1992) 1727–1732.

    PubMed  CAS  Google Scholar 

  38. Oppenheimer, S. M., The anatomy and physiology of cortical mechanisms of cardiac control, Stroke, 24 (1993) 13–15.

    Google Scholar 

  39. Buja, L. M., Eigenbrodt, M. L., and Eigenbrodt, E. H., Apoptosis and necrosis. Basic types and mechanisms of cell death, Arch. Pathol. Lab. Med., 117 (1993) 1208–1214.

    PubMed  CAS  Google Scholar 

  40. Kerr, J. F. R. and Harmon, B. V., Definition and incidence of apoptosis: an historical perspective. In L. D. Tomei and F. O. Cope (eds.) Apoptosis: The Molecular Basis of Cell Death, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1991, pp. 5–29.

    Google Scholar 

  41. Server, A. C. and Mobley, W. C., Neuronal cell death and the role of apoptosis. In L. D. Tornei and F. O. Cope (eds.) Apoptosis: The Molecular Basis of Cell Death, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1991, pp. 263–279.

    Google Scholar 

  42. Baethmann, A., Schurer, L., Unterberg, A., Wahl, W., Staub, F., and Kempski, O. S., Mediator substances of brain edema in cerebral ischemia, Arzneimittelforsch., 41 (1991) 310–315.

    PubMed  CAS  Google Scholar 

  43. Nowak, T. S., Tomida, S., Pluta, R., Xu, S., Kozuka, M., Vass, K., Wagner, H. G., and Klatzo, I., Cumulative effect of repeated ischemia on brain edema in the gerbil, Adv. Neurol., 52 (1990) 1–9.

    PubMed  Google Scholar 

  44. Stummer, W., Baethmann, A., Murr, R., Schurer, L., and Kempski, O. S., Cerebral protection against ischemia by locomotor activity in Gerbils. Underlying mechanisms, Stroke, 26 (1995) 1423–1430.

    PubMed  CAS  Google Scholar 

  45. Ames, A., Wright, R. L., Kowada, M., Thurston, J. M., and Majno, G., Cerebral ischemia, II. The no-reflow phenomenon, Am. J. Pathol., 52 (1968) 437–453.

    PubMed  Google Scholar 

  46. Chiang, J., Kowada, M., Ames, A., Wright, R. L., and Majno, G., Cerebral ischemia, III. Vascular changes, Am. J. Pathol., 52 (1968) 455–476.

    PubMed  CAS  Google Scholar 

  47. Dougherty, J. H., Levy, D. E., and Weksler, B., B. Experimental cerebral ischemia produces platelet aggregation, Neurology, 29 (1979) 1460–1465.

    PubMed  Google Scholar 

  48. Hossmann, V., Hossmann, K.-A., and Tagaki, S., Effect of intravascular platelet aggregation on blood recirculation following prolonged ischemia in the cat brain, J. Neurol., 222 (1980) 159–170.

    PubMed  CAS  Google Scholar 

  49. Hallenbeck, J. M., Dutka, A. J., Tanishima, T., Kochanek, P. M., Kumaroo, K. K., Thompson, C., Obrenovitch, T. P., and Contreas, T. J., Polymorphonuclear leukocyte accumulation in brain regions with low flow during the early post-ischemic period, Stroke, 17 (1986) 246–253.

    PubMed  CAS  Google Scholar 

  50. Grogaard, B., Schurer, L., Gerdin, B., and Arfors, K. E., Delayed hypoperfusion after incomplete forebrain ischemia in the rat: the role of polymorphonuclear leukocytes, J. Cereb. Blood Flow Metab., 9 (1989) 500–505.

    PubMed  CAS  Google Scholar 

  51. Moncada, S. and Vane, J. R., Arachidonic acid metabolites and interactions between platelets and blood vessel walls, N. Engl. J. Med., 300 (1979) 1142–1147.

    PubMed  CAS  Google Scholar 

  52. Black, K. L., Hoff, J. T., and Deshmukh, G. D., Eicosapentaenoic acid: effect on brain prostaglandins, cerebral blood flow and edema in ischemic gerbils, Stroke, 15 (1984) 65–69.

    PubMed  CAS  Google Scholar 

  53. Stevens, M. K., Yaksh, T. L., Hansen, R. B., and Anderson, R. E., Effect of preischemic cyclo-oxygenase inhibition by zomepirac sodium on reflow, cerebral autoregulation, and EEG recovery in the cat after global ischemia, J. Cereb. Blood Flow Metab., 6 (1986) 691–702.

    PubMed  CAS  Google Scholar 

  54. Pettigrew, L. C., Grotta, J. C., Rhoades, H. M., and Wu, K. K., Effect of thromboxane inhibition on eicosanoid levels and blood flow in ischemic rat brain, Stroke, 20 (1989) 627–632.

    PubMed  CAS  Google Scholar 

  55. Nakagomi, T., Sasaki, T., Kirino, T., Tamura, A., Noguchi, M., Saito, I., and Takakura, K., Effects of cyclo-oxygenase and lipo-oxygenase inhibitors on delayed neuronal death in the gerbil hippocampus, Stroke, (1989) 20 925–929.

    PubMed  CAS  Google Scholar 

  56. Wang, X., Tian-Li, Y., Barone, F. C., and Feuerstein, G. Z., Demonstration of increased endothelial-leukocyte adhesion molecule-1 mRNA expression in rat ischemic cortex, Stroke, 26 (1995) 1665–1669.

    PubMed  CAS  Google Scholar 

  57. Zhang, R. L., Chopp, M., Jiang, N., Tang, W. X., Prostak, J., Manning, A. M., and Anderson, D. C., Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the wistar rat, Stroke, 26 (1995) 1438–1443.

    PubMed  CAS  Google Scholar 

  58. Beekhuizen, H. and Furth, R., Monocyte adherence to human vascular endothelium, J. Leukocyte Biol., 54 (1993) 363–378.

    PubMed  CAS  Google Scholar 

  59. Weller, A., Isenmann, S., and Vestwever, D., Cloning of the mouse endothelial selectins: expression of both E- and P-selectin is induced by tumor necrosis factor, J. Biol. Chem.,267 (1992) 15,176–15,183.

    Google Scholar 

  60. Zhang, R. L., Chopp, M., Li, Y., Zaloga, C., Jiang, M., Jones, M., Miyasaka, M., and Ward, P., Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat, Neurology, 44 (1994) 1747–1751.

    PubMed  CAS  Google Scholar 

  61. Flower, R. J., Lipocortin and the mechanism of action of the glucocorticoids, Br. J. Pharmacol., 94 (1988) 987–1015.

    PubMed  CAS  Google Scholar 

  62. Flower, R. J. and Rothwell, N. J., Lipocortin-1: cellular mechanisms and clinical relevance, TIPS, 15 (1994) 71–76.

    PubMed  CAS  Google Scholar 

  63. Go, K. G., Zuiderveen, F., De Ley, L., Ter Haar, J. G., Parente, L., Solito, E., and Molenaar, W. M., Effects of steroids on brain lipocortin immunoreactivity, Acta Neurochir., 60 (1994) 101–103.

    CAS  Google Scholar 

  64. Voermans, P. H., Go, K. G., Ter Horst, G. J., Ruiters, M. H. J., Solito, E., and Parente, L., Induction of annexin-1 mRNA and annexin-1 in rat brain by methylprednisolone and the 21-aminosteroid U74389F, Med. Inflamm.,submitted.

    Google Scholar 

  65. Parente, L. and Solito, E., Association between glucocorticosteroids and lipocortin-1, TIPS, 15 (1994) 362–365.

    PubMed  CAS  Google Scholar 

  66. Russo-Marie, F., Lipocortins: an update, Prostagl. Leukotr. Ess. Fatty Acids, 42 (1991) 83–89.

    CAS  Google Scholar 

  67. Relton, J. K., Strijbos, P. J., O’Shaughnessy, C. T., Carey, F., Forder, R. A., Tilders, F. J., and Rothwell, N. J., Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain, J. Exp. Med., 174 (1991) 305–310.

    Google Scholar 

  68. McKenna, J. A., Lipocortin-1 in apoptosis. Mammary regression, Anat. Rec., 242 (1995) 1–10.

    Google Scholar 

  69. Siesjo, B. K., Zhao, Q., Pahlmark, K., Siesjo, P., Katsura, K., and Folbergrova, J., Glutamate, calcium and free radicals as mediators of ischemic brain damage, Ann. Thorac. Surg. 59 (1995) 1316–1320.

    PubMed  CAS  Google Scholar 

  70. Miljanich, G. P. and Ramachandran, J., Antagonists of neuronal calcium channels: structure, function and therapeutic implications, Annu. Rev. Pharmacol. Toxicol., 35 (1995) 707–734.

    PubMed  CAS  Google Scholar 

  71. Alps, B. J., Drugs acting on calcium channels: potential treatment for ischaemic stroke, Br. J. Clin. Pharmacol., 34 (1992) 199–206.

    PubMed  CAS  Google Scholar 

  72. Ginsberg, M. D., Lin, B., Morikawa, E., Dietrich, W. D., Busto, R., and Globus, M. Y., Calcium antagonists in the treatment of experimental cerebral ischemia, Arzneimittelforschung, 41 (1991) 334–337.

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  74. Morley, P., Hogan, M. J., and Hakim, A. M., Calcium-mediated mechanisms of ischemic injury and protection, Brain Pathol., 4 (1994) 37–47.

    PubMed  CAS  Google Scholar 

  75. Bloom, S., Magnesium deficiency cardiomyopathy, Am. J. Cardiovasc. Pathol., 2 (1988) 7–17.

    PubMed  CAS  Google Scholar 

  76. Maki, A., Berezesky, I. K., Fargnoli, J., Holbrook, N. J., and Trump, B. T., Role of [Ca2+]i in induction of c-fos, c-jun and c-myc mRNA in rat PTE after oxidative stress, FASEB J., 6 (1992) 919–924.

    PubMed  CAS  Google Scholar 

  77. Csermely, P., Schnaider, T., and Szanto, I., Signalling and transport through the nuclear membrane, Biochem. Biophys. Acta, 1241 (1995) 425–452.

    PubMed  Google Scholar 

  78. Paoletti, P., Neyton, J., and Ascher, P., Glycine-independent and subunit-specific potentiation of NMDA responses by extracellular Mgt+, Neuron, 15 (1995) 1109–1120.

    PubMed  CAS  Google Scholar 

  79. Traynelis, S. F., Hartley, M., and Heinemann, S., Control of proton sensitivity of NMDA receptor by RNA splicing and polyamines, Science, 268 (1995) 873–876.

    PubMed  CAS  Google Scholar 

  80. Choi, D. W. and Rothman, S. M., The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death, Ann. Rev. Neurosci.,13 (1990) 171–182.

    Google Scholar 

  81. Meldrum, B. and Garthwaite, J., Excitatory amino acid neurotoxicity and neuro-degenerative disease, Trends Pharmacol. Sci., 11 (1990) 379–387.

    PubMed  CAS  Google Scholar 

  82. Kure, S., Tominaga, T., Yoshimoto, T., Tada, K., and Narisawa, K., Glutamate triggers internucleosomal DNA cleavage in neuronal cells, Biochem. Biophys. Res. Commun., 179 (1991) 39–45.

    PubMed  CAS  Google Scholar 

  83. MacManus, J. P., Hill, I. E., Huang, Z. G., Rasquinha, I., Xue, D., and Buchan, A. M., DNA damage consistent with apoptosis in transient focal ischaemic cortex, NeuroReport, 5 (1994) 493–496.

    PubMed  CAS  Google Scholar 

  84. Ankarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., and Nicotera, P., Glutamate induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function, Neuron, 15 (1995) 961–973.

    PubMed  CAS  Google Scholar 

  85. Wood, E. R., Bussey, T. J., and Phillips, A. G., A glycine antagonist 7-chlorokynurenic acid attenuates ischemia-induced learning deficits, NeuroReport, 4 (1993) 151–154.

    PubMed  CAS  Google Scholar 

  86. Pellegrini-Giampietro, D. E., Cozzi, A., and Moroni, F., The glycine antagonist and free radical scavenger 7-C1-thio-kynurnate reduces CAI ischemic damage in the gerbil, Neuroscience, 63 (1994) 701–709.

    PubMed  CAS  Google Scholar 

  87. Patel, M., Day, B. J., Crapo, J. D., Fridovich, I., and McNamara, J. O., Requirement for superoxide in excitotoxic cell death, Neuron, 16 (1996) 345–355.

    PubMed  CAS  Google Scholar 

  88. Hatfield, R. H., Gill, R., and Brazell, C., The dose-response relationship and therapeutic window for dizocilpine (MK-801) in a rat focal ischemia model, Eur. J. Pharmacol., 216 (1992) 1–7.

    PubMed  CAS  Google Scholar 

  89. Hewitt, K. and Corbett, D., Combined treatment with MK-801 and nicardipine reduces global ischemic damage in the gerbil, Stroke, 23 (1992) 82–86.

    PubMed  CAS  Google Scholar 

  90. Uematsu, D., Araki, N., Greenberg, J. H., Sladky, J., and Reivich, M., Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage, Neurology, 41 (1991) 88–94.

    PubMed  CAS  Google Scholar 

  91. Lyden, P. D. and Lonzo, L., Combination therapy protects ischemic brain in rats. A glutamate antagonist plus a gamma-aminobutyric acid agonist, Stroke, 25 (1994) 189–196.

    PubMed  CAS  Google Scholar 

  92. Javitt, D. C. and Zukin, S. R., Recent advances in the phencyclidine model of schizophrenia, Am. J. Psychiat., 148 (1991) 1301–1308.

    PubMed  CAS  Google Scholar 

  93. Kinouchi, H., Sharp, F. R., Chan, P. H., Mikawa, S., Kamii, H., Arai, S., and Yoshimoto, T., MK-801 inhibits the induction of immediate early genes in cerebral cortex, thalamus, and hippocampus, but not in the substantia nigra following middle cerebral artery occlusion, Neurosci. Lett., 179 (1994) 111–114.

    PubMed  CAS  Google Scholar 

  94. Vendrell, M., Curran, T., and Morgan, J. I., Glutamate, immediate early genes, and cell death in the central nervous system, Ann. NY Acad. Sci., 679 (1993) 132–141.

    Google Scholar 

  95. Swanson, R. A., Yu, A. C. H., Chan, P. H., and Sharp, F. R., Glutamate increases glycogen content and reduces glucose utilization in primary astrocyte cultures, J. Neurochem., 54 (1990) 490–496.

    PubMed  CAS  Google Scholar 

  96. Elekes, O., Venema, K., Postema, F., Dringen, R., Hamprecht, B., and Korf, J., Glial contribution of rat hippocampus lactate as assessed with microdialysis and stress, Neurosci. Lett. (1996), in press.

    Google Scholar 

  97. Cornell-Bell, A. H., Finkbeiner, S. M., Cooper, M. S., and Smith, S. J., Glutamate induces calcium waves in cultured astrocytes: long range glial signaling, Science, 247 (1990) 470–473.

    PubMed  CAS  Google Scholar 

  98. Glaum, S. R., Holzwarth, J. A., and Miller, R. J., Glutamate receptors activate Cat+ mobilization and Cat+ influx in astrocytes, Proc. Natl. Acad. Sci. USA, 87 (1990) 3454–3458.

    PubMed  CAS  Google Scholar 

  99. Rosenberg, P. A. and Aizenman, E., Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of rat cerebral cortex, Neurosci. Lett., 103 (1989) 162–168.

    PubMed  CAS  Google Scholar 

  100. Rosenberg, P. A., Accumulation of extracellular glutamate and neuronal death in astrocyte-poor cortical cultures exposed to glutamine, Glia, 4 (1991) 91–100.

    PubMed  CAS  Google Scholar 

  101. Volterra, A., Trotti, D., Cassutti, P., Tromba, C., Salvaggio, A., Melcangi, R. C., and Racagni, G., High sensitivity of glutamate uptake to extracellular free arachidonic acid levels in rat cortical synaptosomes and astrocytes, J. Neurochem., 59 (1992) 600–606.

    PubMed  CAS  Google Scholar 

  102. Dugan, L. L., Bruno, V. M. G., Amagasu, S. M., and Giffard, R. G., Glia modulate the response of murine cortical neurons to excitotoxicity: glia exacerbate AMPA neurotoxicity. J. Neurosci., 15 (1995) 4545–4555.

    PubMed  CAS  Google Scholar 

  103. Eng, L. F., Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes, J. Neuroimmunol., 8 (1985) 203–214.

    PubMed  CAS  Google Scholar 

  104. Lindsay, R. M., Reactive gliosis. In S. Federoff and A. Vernadakis (eds.) Astrocytes: Cell, Biology and Pathology of Astrocytes, vol. 3, Academic Press, Orlando, FL, 1986, pp. 231–262.

    Google Scholar 

  105. Wood, P. L., Microglia as a unique cellular target in the treatment of stroke: potential neurotoxic mediators produced by activated microglia, Neurol. Res., 17 (1995) 242–248.

    PubMed  CAS  Google Scholar 

  106. Schwartz, J. P., Sheng, J. G., Mitsuo, K., Shirabe, S., and Nishiyama, N., Trophic factor production by reactive astrocytes in injured brain, Ann. NY Acad. Sci. NY, 679 (1993) 226–234.

    CAS  Google Scholar 

  107. Morrison, R. S., Sharma, A., De Vellis, J., and Bradshaw, R. A., Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture, Proc. Natl. Acad. Sci. USA, 83 (1986) 7537–7541.

    PubMed  CAS  Google Scholar 

  108. Maiese, K., Boniece, I., DeMeo, D., and Wagner, J. A., Peptide growth factors protect against ischemia in culture by preventing nitric oxide toxicity, J. Neurosci. 13 (1993) 3034–3040.

    PubMed  CAS  Google Scholar 

  109. Pechan, P. A., Chowdhury, K., Gerdes, W., and Seifert, W., Glutamate induces the factors NGF, bFGF, the receptor FGF-R1 and c-fos mRNA expression in rat astrocytes in culture, Neurosci. Lett., 153 (1993) 111–114.

    PubMed  CAS  Google Scholar 

  110. Mattson, M. P. and Scheff, S. W., Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy, J. Neurotrauma, 11 (1994) 3–33.

    PubMed  CAS  Google Scholar 

  111. Hsu, C. Y., An, G., Liu, J. S., Xue, J. J., He, Y. Y., and Lin, T. N., Expression of immediate early gene and growth factor mRNAs in a focal cerebral ischemia model in the rat, Stroke, 24 (1993) 178–181.

    Google Scholar 

  112. Takeda, A., Onodera, H., Sugimoto, A., Kogure, K., Obinata, M., and Shibahara, S., Coordinated expression of messenger RNAs for nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia, Neuroscience, 55 (1993) 23–31.

    PubMed  CAS  Google Scholar 

  113. Dragunow, M., Beilharz, E., Sirimanne, E., Lawlor, P., Williams, C., Bravo, R., and Gluckman, P., Immediate early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischemic injury to the young rat brain, Mol. Brain Res., 25 (1994) 19–33.

    PubMed  CAS  Google Scholar 

  114. Koh, J. Y., Gwag, B. J., Lobner, D., and Choi, D., W. Potentiated necrosis of cultured cortical neurons by neurotrophins, Science, 268 (1995) 573–575.

    PubMed  CAS  Google Scholar 

  115. Halliwell, B. and Gutteridge, J. M. C., Free Radicals in Biology and Medicine, Oxford University Press, London, 1985.

    Google Scholar 

  116. Patt, A., Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusioninduced edema in gerbil brains, J. Clin. Invest., 81 (1988) 1556–1562.

    PubMed  CAS  Google Scholar 

  117. Siesjo, B. L., Agardh, C. D., and Bengtson, F., Free radicals and brain damage, Cereb. Brain Metab. Rev., 1 (1989) 165–211.

    CAS  Google Scholar 

  118. Agardh, C. D., Zhang, H., Smith, M. L., and Siesjo, B. L., Free radical production and ischemic brain damage: influence of post-ischemic oxygen tension, Int. J. Dev. Neurosci., 9 (1991) 127–138.

    PubMed  CAS  Google Scholar 

  119. Damsma, G., Boisvert, D. P., Mudrick, L. A., Wenkstern, D., and Fibiger, H. C., Effects of transient forebrain ischemia and pargyline on extracellular concentrations of dopamine, serotonine, and their metabolites in the rat striatum as determined by in vivo microdialysis, J. Neurochem., 54 (1990) 801–808.

    PubMed  CAS  Google Scholar 

  120. Gutteridge, J. M. C., Hydroxyl radicals, iron, oxidative stress and neurodegeneration, Ann. NY Acad. Sci., 738 (1994) 201–213.

    PubMed  CAS  Google Scholar 

  121. Palmer, R. M. J., Ashton, D. S., and Moncada, S., Vascular endothelial cells synthesize nitric oxide from 1-arginine, Nature, 333 (1988) 664–666.

    PubMed  CAS  Google Scholar 

  122. Palmer, R. M. J., Ferrige, A. G., and Moncada, S., Nitric oxide release account for the biological activity of endothelium-derived relaxing factor, Nature, 327 (1987) 524–526.

    PubMed  CAS  Google Scholar 

  123. Ischiropoulos, H., Zhu, L., and Beckman, J. S., Peroxynitrite formation from macrophage-derived nitric oxide, Arch. Biochem. Biophys., 208 (1992) 446–451.

    Google Scholar 

  124. Ter Horst, G. J., Knollema, S., Stuiver, B., Hom, H. W., Yoshimura, S., Ruiters, M. H. J., and Korf, J., Differential glutathione peroxidase mRNA up-regulations in rat forebrain areas after transient hypoxia/ischemia, Ann. NYAcad. Sci. USA, 738 (1994) 329–333.

    Google Scholar 

  125. Moreno, S. and Muganini, E, Immunocytochemical localization of catalase in rat brain, Soc. Neurosci. Abstr., 18 (1992) 1604.

    Google Scholar 

  126. Knollema, S., Horn, H. W., Schirmer, H., Korf, J., and Ter Horst, G. J., Immunolocalization of glutathione reductase in the murine brain, J. Comp. Neurol. (1996), in press.

    Google Scholar 

  127. Mahadik, S. P., Makar, T. K., Murthy, J. N., and Karplak, S. E., Temporal changes in superoxide dismutase, glutathione peroxidase and catalase levels in primary and periischemic tissue: monosialoganglioside (GM1) treatment effects, Mol. Chem. Neuropathol., 18 (1993) 1–14.

    PubMed  CAS  Google Scholar 

  128. Matsuyama, T., Michishita, H., Nakamura, N., Tsuchiyama, M., Shimizu, S., Watanabe, K., and Sugita, M., Induction of copper-zinc superoxide dismutase in gerbil hippocampus after ischemia, J. Cereb. Blood Flow Metab., 13 (1993) 135–144.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  130. Truelove, D., Shuaib, A., Ijaz, S., Ishaqzay, R., and Kalra, J., Neuronal protection with superoxide dismutase in repetitive forebrain ischemia in gerbils, Free Radic. Biol. Med., 17 (1994) 445–450.

    PubMed  CAS  Google Scholar 

  131. He, Y. Y., Hsu, C. Y., Ezrin, A. M., and Miller, M. S., Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia-reperfusion, Am. J. Physiol., 265 (1993) H252–256.

    PubMed  CAS  Google Scholar 

  132. Knollema, S., Elting, J. W., Korf, J., and Ter Horst, G. J., Ebselen (PZ-51) protects the caudate putamen against hypoxia/ischemia induced neuronal damage, Neurosci. Res. Comm. (1996), in press.

    Google Scholar 

  133. Yue, T. L., Gu, J. L., Lysko, P. G., Cheng, H. Y., Barone, F. C., and Feuerstein, G., Neuroprotective effects of phenyl-t-butyl-nitrone in gerbil global brain ischemia and in cultured rat cerebellar neurons, Brain Res., 574 (1992) 193–197.

    PubMed  CAS  Google Scholar 

  134. Kinouchi, H., Epstein, C. J., Mizui, T., and Chan, P. H., Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing Cu/Zn-superoxide dismutase, Proc. Natl. Acad. Sci. USA,88 (1991) 11,158–11,162.

    Google Scholar 

  135. Knollema, S., Aukema, W., Horn, H. W., Korf, J., and Ter Horst, G. J., L-Deprenyl reduces brain damage in rats exposed to transient hypoxia/ischemia, Stroke,26 (1995) 1883–1888.

    Google Scholar 

  136. Sivenius, J., Kuhmonen, J., Miettinen, R., Baapalinna, A., and Riekkinen, P. J., Effect of selegeline on the hippocampal CA1 layer following transient ischemia in gerbils, Soc. Neurosci. Abstr., 20 (1994) 188.

    Google Scholar 

  137. Carillo, M. C., Kanai, S., Nokubo, M., and Kitani, K., (—)Deprenyl induces activities of both superoxide dismutase and catalase but not glutathione peroxidase in the striatum of young male wistar rats, Life Sci.,48 (1991) 517–521.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  139. Knollema, S., Van de Witte, S. V., Korf, J., and Ter Horst, G. J., The reaction of microglia and astrocytes in relation to the development of regional neuronal damage after ischemia, J. Comp. Neurol.,submitted.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  141. Jander, S., Kraemer, M., Schroeter, M., Witte, O. W., and Stoll, G., Lymphocyte infiltration and expression of intercellular adhesion molecule 1 in photochemically induced ischemia of the rat cortex, J. Cereb. Blood Flow Metabol., 15 (1995) 42–51.

    CAS  Google Scholar 

  142. Korematsu, K., Goto, S., Nagahiro, S., and Ushio, Y., Microglial response to transient focal cerebral ischemia: an immunocytochemical study on rat cerebral cortex using antiphosphotyrosine antibody, J. Cereb. Blood Flow Metabol., 14 (1994) 825–830.

    CAS  Google Scholar 

  143. Wang, X., Yue, T. L., Barone, F. C., and Feuerstein, G. Z., Demonstration of increased endothelial-leukocyte adhesion molecule-1 mRNA expression in rat ischemic cortex, Stroke, 26 (1995) 1665–1669.

    PubMed  CAS  Google Scholar 

  144. Guilian, D., Baker, T. J., Shih, L., and Lachman, L. B., Interleukin-1 of the central ner- vous system is produced by ameboid microglia, J. Exp. Med.,164 (1987) 594–604.

    Google Scholar 

  145. Sawada, M., Kondo, N., Suzumura, A., and Marunouchi, T., Production of tumor necrosis factor-alpha by microglia and astrocytes in culture, Brain Res., 491 (1989) 394–397.

    PubMed  CAS  Google Scholar 

  146. Woodroofe, M. N., Santa, G. S., Wadhwa, M., Hayes, G. M., Loughlin, A. J., Tinker, A., and Cuzner, M. ., Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production, J. Neuroimmunol., 33 (1991) 227–236.

    PubMed  CAS  Google Scholar 

  147. Wong, G. H. W., Protective roles of cytokines against radiation: Induction of mitochondria) MnSOD, Biochem. Biophys. Acta, 1271 (1995) 205–209.

    PubMed  Google Scholar 

  148. Cheng, B., Christakos, S., and Mattson, M. P., Tumor necrosis factor protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis, Neuron, 12 (1994) 139–153.

    PubMed  CAS  Google Scholar 

  149. Tchelingerian, J. L., Quinonero, J., Booss, J., and Jacque, C., Localization of TNFa and IL-la immunoreactivities in striatal neurons after surgical injury to the hippocampus, Neuron, 10 (1993) 213–224.

    PubMed  CAS  Google Scholar 

  150. Sharkey, J. and Butcher, S. P., Immunophilins mediate the neuroprotective effects of FK506 in focal cerebral ischemia, Nature, 371 (1994) 336–339.

    PubMed  CAS  Google Scholar 

  151. Minami, M., Kuraishi, Y., Yabuuchi, K., Yamazaki, K., and Satoh, M., Induction of interleukin-lb mRNA in rat brain after transient forebrain ischemia, J. Neurochem., 58 (1992) 390–394.

    PubMed  CAS  Google Scholar 

  152. Rothwell, N. J. and Strijbos, P. J. L. M., Cytokines in neurodegeneration and repair, Int. J. Devl. Neurosci., 13 (1995) 179–185.

    CAS  Google Scholar 

  153. Lindholm, D., Heumann, R., Meyer, M., and Thoenen, H., Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve, Nature, 230 (1987) 658, 659.

    Google Scholar 

  154. Wong, D. and Dorovini-Zis, K., Upregulation of intercellular adhesion molecule-1(ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide, J. Neuroimmunol., 39 (1992) 11–22.

    PubMed  CAS  Google Scholar 

  155. Rothwell, N. J. and Relton, J. K., Involvement of cytokines in acute neurodegeneration in tr ’ CNS, Neurosci. Behay. Res., 17 (1993) 217–227.

    CAS  Google Scholar 

  156. Qauglirello, V. J., Wispelwey, B., Long, W. J., and Scheld, W. M., Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat, J. Clin. Invest., 87 (1991) 1360–1366.

    Google Scholar 

  157. Fan, L., Young, P. R., Barone, F. C., Feuerstein, G. Z., Smith, D. H., and McIntosh, T. K., Experimental brain injury induces expression of interleukin-lb mRNA in the rat brain, Mol. Brain Res., 30 (1995) 125–130.

    PubMed  CAS  Google Scholar 

  158. Tracey, K. J. and Cerami, A., Tumor necrosis factor, other cytokines and disease, Ann. Rev. Cell Biol., 9 (1993) 317–343.

    PubMed  CAS  Google Scholar 

  159. Oehm, A., Behrmann, I., Falk, W., Pawlita, M., Maier, G., Klas, C., Li-Weber, M., Richards, S., Dhein, J., and Trauth, B. C., Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor family, J. Biol. Chem.,267 (1992) 10,709–10,715.

    Google Scholar 

  160. Dickson, D. W., Apoptosis in the brain, Am. J. Pathol., 146 (1995) 1040–1044.

    PubMed  CAS  Google Scholar 

  161. Matsuyama, T., Hata, R., Tagaya, M., Yamamoto, Y., Nakajima, T., Furuyama, J., Wanake, A., and Sugita, M., Fas antigen mRNA induction in postischemic murine brain, Brain Res., 657 (1994) 342–346.

    PubMed  CAS  Google Scholar 

  162. Weller, M., Frei, K., Groscurth, P., Krammer, P. H., Yonekawa, Y., and Fontana, A., Anti-Fas/APO-1 antibody mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines, J. Clin. Invest., 94 (1994) 954–964.

    PubMed  CAS  Google Scholar 

  163. D’Souza, S. D., Antel, J. P., and Freedman, M. S., Cytokine induction of heat shock protein expression in human oligodendrocytes: an interleukin-1 mediated mechanism, J. Neuroimmunol., 50 (1994) 17–24.

    PubMed  Google Scholar 

  164. Nowak, T. S., Synthesis of heat shock/stress protein during cellular injury, Ann. NYAcad. Sci., 679 (1993) 142–156.

    CAS  Google Scholar 

  165. Kerr, J. F. R., Wyllie, A. H., and Currie, A. R., Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics, Br. J. Cancer, 26 (1972) 239–257.

    PubMed  CAS  Google Scholar 

  166. Martin, D. P., Schmidt, R. E., DiStefano, P. S., Lowry, O. H., Carter, J. G., Johnson, E. M., Jr, Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation, J. Cell Biol., 106 (1988) 829–844.

    PubMed  CAS  Google Scholar 

  167. Jacobsen, M. D., Burne, J. F., and Raff, M. C., Programmed cell death and Bc1–2 protection in the absence of a nucleus, EMBO J., 13 (1994) 1899–1910.

    Google Scholar 

  168. Steller, H., Mechanisms and genes of cellular suicide, Science, 267 (1995) 1445–1449.

    PubMed  CAS  Google Scholar 

  169. Wyllie, A. H., Kerr, J. F. R., and Currie, A. R., Cell death: the significance of apoptosis, Int. Rev. Cytol., 68 (1980) 251–306.

    PubMed  CAS  Google Scholar 

  170. Smeyne, R. J., Vendrell, M., Hayward, M., Baker, S. J., Miao, G. G., Schilling, K., Robertson, L. M., Curran, T., and Morgan, J. I., Continuous c-fos expression precedes programmed cell death in vivo, Nature, 363 (1993) 166–169.

    PubMed  CAS  Google Scholar 

  171. Estus, S., Zaks, W. J., Freeman, R. S., Gruda, M., Bravo, R., and Johnson, E. M., Jr., Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis, J. Cell Biol., 127 (1994) 1717–1727.

    PubMed  CAS  Google Scholar 

  172. Ham, J., Babij C., Whitfield J., Pfarr, C. M., Lallemand, D., Yaniv, M., and Rubin, L. L., A c-jun dominant negative mutant protects sympathetic neurons against programmed cell death, Neuron, 14 (1995) 927–939.

    PubMed  CAS  Google Scholar 

  173. Debbas, M. and White, E., Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B, Genes amp; Dev., 7 (1993) 546–554.

    CAS  Google Scholar 

  174. Yonish-Rouach, E., Resnitzki, D., Lotem, J., Sachs, L., Kimchi, A., and Oren, M., Wildtype p53 induces apoptosis of myeloid leukemic cells that is inhibited by interleukin 6, Nature, 352 (1991) 345–347.

    PubMed  CAS  Google Scholar 

  175. Freeman, R. S., Estus, S., Johnson, E. M., Jr., Analysis of cell cycle related gene expression in postmitotic neurons, Neuron, 12 (1994) 343–355.

    PubMed  CAS  Google Scholar 

  176. Shi, L., Nishioka, W. K., Th’ng, J., Bradbury, E. M., Litchfield, D. W., and Greenberg, A. H., Premature p34cdc2 activation required for apoptosis, Science, 263 (1994) 1143–1145.

    PubMed  CAS  Google Scholar 

  177. Evan, G. I., Wyllie, A. H., Gilbert, C. S., Littlewood, T. D., Land, H., Brooks, M., Waters, C. M., Penn, L. Z., Hancock, D. C., Induction of apoptosis in fibroblasts by c-myc protein, Cell, 69 (1992) 119–128.

    PubMed  CAS  Google Scholar 

  178. Bissonnette, R. P., Echeverri, F., Mahboubi, A., and Green, D. R., Apoptotic cell death induced by c-myc is inhibited by bc1–2, Nature, 359 (1992) 552–553.

    PubMed  CAS  Google Scholar 

  179. Rubin, L. L., Gatchalian, C. L., Rimon, G., and Brooks, S. F., The molecular mechanisms of neuronal apoptosis, Curr. Opin. Neurobiol., 4 (1994) 696–702.

    PubMed  CAS  Google Scholar 

  180. Yuan, J. and Horvitz, H. R., The Caenorhabitis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death, Development, 116 (1992) 309.

    PubMed  CAS  Google Scholar 

  181. Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., Kostura, M. J., Miller, D. K., Milineaux, S. M., Weidner, J. R., and Aunins, J., A novel heterodimeric cysteine protease is required for interleukin 143 processing in monocytes, Nature, 356 (1992) 768–774.

    PubMed  CAS  Google Scholar 

  182. Yuan, J., Shaham, S., Ledoux, S., Ellis, H. M., and Horvitz, H. R., The C. elegans cell death gene ced-3 encodes a protein similar to mammalian Interleukin 1–13 Converting Enzyme, Cell, 75 (1993) 641–652.

    PubMed  CAS  Google Scholar 

  183. Wang, L., Miura, M., Bergeron, L., Zhu, H., and Yuan, J., Ich-1 an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death, Cell, 78 (1994) 739–750.

    PubMed  CAS  Google Scholar 

  184. Fernandez-Alnemri, T., Litwack, G., and Alnemri, E. S., CPP32 a novel human apoptotic protein with homology to Caenorhabitis elegans cell death protein ced-3 and mammalian Interleukin 1–3 Converting Enzyme, J. Biol. Chem.,269 (1994) 30,761–30,764.

    Google Scholar 

  185. Miura, M., Zhu, H., Rotello, R., Hartwieg, E. A., and Yuan, J., Induction of apoptosis in fibroblasts by Il-1–13-Converting Enzyme, a mammalian homolog of the C. elegans cell death gene ced-3, Cell, 75 (1993) 653–660.

    PubMed  CAS  Google Scholar 

  186. Gagliardini, V., Fernandez, P. A., Lee, R. K. K., Drexler, H. C. A., Rotello, R. J., Fishman, M. C., and Yuan, J., Prevention of vertebrate neuronal death by the crmA gene, Science, 263 (1994) 826–828.

    PubMed  CAS  Google Scholar 

  187. Hengartner, M. O., Ellis, R. E., and Horvitz, H. R., Caenorhabitis elegans gene ced-9 protects cells from programmed cell death, Nature, 356 (1992) 494–499.

    PubMed  CAS  Google Scholar 

  188. Hengartner, M. O. and Horvitz, H. R., C. elegans cell survival gene encodes a functional homolog of the mammalian proto-oncogene bc1–2, Cell, 76 (1994) 665–676.

    PubMed  CAS  Google Scholar 

  189. Batistatou, A., Merry, D. E., Korsmeyer, S. J., and Greene, L. A., Bc1–2 affects survival but not neuronal differentiation of PC12 cells, J. Neurosci., 13 (1993) 4422–4428.

    PubMed  CAS  Google Scholar 

  190. Mah, S. P., Zhong, L. T., Liu, Y., Roghani, A., Edwards, R. H., and Bredesen, D. E., The proto-oncogen bcl-2 inhibits apoptosis in PC12 cells, J. Neurochem., 60 (1993) 1183–1186.

    PubMed  CAS  Google Scholar 

  191. Garcia, I., Martinou, I., Tsujimoto, Y., and Martinou, J. C., Prevention of programmed cell death of sympathetic neurons by the bc1–2 proto-oncogene, Science, 258 (1992) 302–304.

    Google Scholar 

  192. Allsopp, T. E., Wyatt, S., Paterson, H. F., and Davies, A. M., The proto-oncogene bc1–2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis, Cell, 73 (1993) 295–307.

    PubMed  CAS  Google Scholar 

  193. Martinou, J. C., Dubois-Dauphin, M., Staple, J. K., Rodriguez, I., Frankowski, H. Misotten, M., Albertini, P., Talabot, D., Catsicas, S., and Pietra, C., Overexpression of Bc1–2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischaemia, Neuron, 13 (1994) 1017–1030.

    PubMed  CAS  Google Scholar 

  194. Clem, R. J., Fechheimer, M., and Miller, L. K., Prevention of apoptosis by a Baculovirus gene during infection of insect cells, Science, 254 (1991) 1388–1390.

    PubMed  CAS  Google Scholar 

  195. Sugimoto, A., Friesen, P. D., and Rothman, J. H., Baculovirus p35 prevents developmentally programmed cell death and rescues a ced9 mutant in the nematode Caenorhabitis elegans, EMBO J., 13 (1994) 2023–2028.

    CAS  Google Scholar 

  196. Rabizadeh, S., LaCount, D. J., Friesen, P. D., and Bredesen, D. E., Expression of the Baculovirus p35 gene inhibits mammalian neural cell death, J. Neurochem., 61 (1993) 2318–2321.

    PubMed  CAS  Google Scholar 

  197. Davies, A. M., The Bc1–2 family of proteins and the regulation of neuronal survival, Trends Neurosci., 18 (1995) 355–358.

    PubMed  CAS  Google Scholar 

  198. Oltvai, Z. N., Milliman, C. L., and Korsmeyer, S. J., Bc1–2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death, Cell, 74 (1993) 609–619.

    PubMed  CAS  Google Scholar 

  199. Yin, X. M., Oltvai, Z. N., and Korsmeyer, S. J., BH1 and BH2 domains of Bc1–2 are required for ihibition of apoptosis and heterodimerization with Bax, Nature, 369 (1994) 321–323.

    PubMed  CAS  Google Scholar 

  200. Sato, T., Hanada, M., Bodrug, S., Jrie, S., Jwama, N., Boise, L. H., Thompson, C. B., Golemis, E., Fong, L., and Wang, H. G., Interactions among members of the Bc1–2 protein family analyzed with a yeast two-hybrid system. Proc. Natl. Acad. Sci. USA, 91 (1994) 9238–9242.

    PubMed  CAS  Google Scholar 

  201. Barinaga, M., Cell suicide: by ICE, not fire, Science, 263 (1994) 754–756.

    PubMed  CAS  Google Scholar 

  202. Boise, L. H., Gonzalez, G. M., Postema, C. E., Ding, L., Lindsten, T., Turka, L. A., Mao, X., Nunez, G., and Thompson, C., B. bc1-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death, Cell, 74 (1993) 597–608.

    PubMed  CAS  Google Scholar 

  203. Motoyama, N., Wang, F., Roth, K. A., Sawa, H., Nakayama, K., Nakayama, K.,Negishi, I., Senju, S., Zhang, Q., Fujii, S., and Loh., D. Y., Massive cell death of immature hematopoietic cells and neurons in Bc1-x deficient mice, Science, 267 (1995) 1506–1510.

    PubMed  CAS  Google Scholar 

  204. Krajewski, S., Mai., J. K., Krajewska, M., Sikorska, M., Mossakowski, M. J., and Reed, J. C., Upregulation of Bax protein levels in neurons following cerebral ischaemia, J. Neurosci. 15 (1995) 6364–6376.

    PubMed  CAS  Google Scholar 

  205. Honkaniemi, J., Massa, S. M., and Sharp, F. R., Sequential induction of specific apoptosisassociated genes in gerbil CAI pyramidal hippocampal neurons following global ischaemia, J. Cereb. Blood Flow Metab., 15 (1995) S148.

    Google Scholar 

  206. Krajewski, S., Tanaka, S., Takayama, S., Schibler, M. J., Fenton, W., and Reed, J. C., Investigations of the subcellular distribution of the bcl-2oncoprotein: residence in the nuclear envelope, endoplasmatic reticulum, and outer mitochondrial membranes, Cancer Res., 53 (1993) 4701–4714.

    PubMed  CAS  Google Scholar 

  207. Lam, M., Dubyak, G., Chen, L., Nunez, G., Miesfeld, R. L., and Distelhorst, D. W., Evidence that Bc1–2 represses apoptosis by regulating endoplasmatic reticulum-associated Cat+ fluxes, Proc. Natl. Acad. Sci. USA, 91 (1994) 6569–6573.

    PubMed  CAS  Google Scholar 

  208. Hockenberry, D., Oltvai, Z., Yin, X. M., Milliman, C., and Korsmeyer, S. J., Bc1–2 functions in an antioxidant pathway to prevent apoptosis, Cell, 75 (1993) 241–251.

    Google Scholar 

  209. Kane, D. J., Sarafin, T. A., Auton, S., Hahn, H., Gralla, F. B., Valentine, J. C., Ord, T., and Bredesen, D. E., Bc1–2 inhibition of neural cell death: decreased generation of reactive oxygen species, Science, 262 (1993) 1274–1276.

    PubMed  CAS  Google Scholar 

  210. Fernandez-Sarabia, M. and Bischoff, J. R., Bc1–2 associates with the ras-related protein R-ras p23, Nature, 366 (1993) 274, 275.

    Google Scholar 

  211. Bunyan, R., Zakeri, Z., Lockshin, R., and Wohlgemuth, D., Cascade induction of c-fos, c-myc and heat shock 70 K transcripts during regression of the rat ventral prostate gland, Mol. Endocrinol., 2 (1988) 650–657.

    Google Scholar 

  212. Dragunow, M. and Preston, K., The role of inducible transcription factors in apoptotic nerve cell death, Brain Res. Rev., 21 (1995) 1–28.

    PubMed  CAS  Google Scholar 

  213. DeFelipe, C. and Hunt, S. P., The differential control of c-jun expression in regenerating sensory neurons and their associated glial cells, J. Neurosci., 14 (1994) 2911–2923.

    CAS  Google Scholar 

  214. Anderson, A. J., Pike, C. J., and Cotman, C. W., Differential induction of immediate early gene proteins in cultured neurons by ß-Ameloid (Aß): association of c-jun with Aß-induced apoptosis, J. Neurochem., 65 (1995) 1487–1498.

    PubMed  CAS  Google Scholar 

  215. Wiessner, C., Cyclin Dl—a gene associated with programmed cell death in sympathetic ganglion neurons—is expressed in the postischemic rat brain, J. Cereb. Blood Flow Metab., 15 (1995) S146.

    Google Scholar 

  216. Schreiber, S. S., Sakhi, S., Dugich-Djordjevic, M. M., and Nichols, N. R., Tumor suppressor p53 induction and DNA damage in hippocampal granule cells after adrenalectomy, Exp. Neurol., 130 (1994) 368–376.

    PubMed  CAS  Google Scholar 

  217. Yonish-Rouach E., Wilder, S., Kimchi, A., May, E., Lawrence, J. J., May, P., and Oren, M., p53-mediated cell death: relationship to cell cycle control, Mol. Cell Biol., 13 (1993) 1415–1423.

    PubMed  CAS  Google Scholar 

  218. El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. S., Parsons, R., Trent, J. M., Lin, D. T., Mercer, W. E., Kinzler, K. W., and Vogelstein, B., WAF1 a potential mediator of p53 tumor suppression, Cell, 75 (1993) 817–825.

    PubMed  CAS  Google Scholar 

  219. Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K., and Elledge, S. J., The p21 cdkinteracting protein Cipl is a potent inhibitor of G1 cyclin-dependent kinases, Cell, 75 (1993) 805–816.

    PubMed  CAS  Google Scholar 

  220. Sherr, C. J. and Roberts, J. M., Inhibitors of mammalian G1 cyclin-dependent kinases, Genes amp; Dev., 9 (1995) 1149–1163.

    CAS  Google Scholar 

  221. Davis, R. J., MAPKs: new JNK expands the group, Trends Biochem. Sci., 19 (1994) 470–473.

    PubMed  CAS  Google Scholar 

  222. Nobes, C. D., Reppas, J. B., Markus, A., and Tolkovsky, A. M., Active p21 Ras is sufficient for rescue of NGF-dependent rat sympathetic neurons, Neuroscience, 70 (1996) 1067–1079.

    PubMed  CAS  Google Scholar 

  223. Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., and Greenberg, M. E., Opposing effects of ERK and JNK-p38 MAR kinases on apoptosis, Science, 270 (1995) 1326–1331.

    PubMed  CAS  Google Scholar 

  224. White, K., Grether, M. E., Abrams, J. M., Young, L., Farrell, K., and Steller, H., Genetic control of programmed cell death in Drosophila, Science, 264 (1994) 677–683.

    CAS  Google Scholar 

  225. Heintz, N., Cell death and the cell cycle: a relationship between transformation and neurodegeneration?, Trends Biochem. Sci., 18 (1993) 157–159.

    Google Scholar 

  226. Feddersen, R. M., Ehlenfeldt, R., Yunis, W. S., Clark, H. B., and Orr, H. T., Disrupted cerebellar cortical development and progressive degeneration of purkinje cells in SV40 T antigen transgenic mice, Neuron, 9 (1992) 955–966.

    PubMed  CAS  Google Scholar 

  227. Lee, E. Y., Chang, C. Y., Hu, N., Wong, Y. C., Lai, C. C., Herrup, K., Lee, W. H., and Bradley, A., Mice deficient for Rb are nonviable and show defects in neurogenesis and hemotopoiesis, Nature, 359 (1992) 288–294.

    PubMed  CAS  Google Scholar 

  228. Herrup, K. and Busser, J. C., The induction of multiple cell cycle events precedes target-related neuronal death, Development, 121 (1995) 2385–2395.

    PubMed  CAS  Google Scholar 

  229. Ross, M. E., Cell division and the nervous system: regulating the cycle from neural differentiation to death, Trends Neurosci., 19 (1996) 62–68.

    PubMed  CAS  Google Scholar 

  230. Farinelli, S. E. and Greene, L. A., Cell cycle blockers Mimosine, Ciclopirox, and Deferoxamine prevent the death of PC 12 cells and postmitotic sympathetic neurons after removal of trophic support, J. Neurosci., 16 (1996) 1150–1162.

    PubMed  CAS  Google Scholar 

  231. Thompson, C. B., Apoptosis in the pathogenesis and treatment of disease, Science, 267 (1995) 1456–1462.

    PubMed  CAS  Google Scholar 

  232. Verheul, H. B., Balazs, R., Berkerbach van Sprenkel, J. W., Tulleken, C. A. F., Nicolay, K., Tamminga, K. S., and Van Lookeren Campagne, M., Comparison of diffusion-weighted MRI with changes in cell volume in a rat model of brain injury, NMR in BioMed., 7 (1994) 96–100.

    CAS  Google Scholar 

  233. Ter Horst, G. J., Knollema, S., Knigge, M. F., Krugers, H. J., Van de Witte, S. V., Postema, F., and Horn, H. W., Silver staining of traumatized neurons: application of a Gallyas procedure in experimental cerebral hypoxia/ischemia research, Neurosci. Prot., 050–02 (1995) 1–13.

    Google Scholar 

  234. Krugers, H. J., Medema, R. M., Postema, F., and Korf, J., Induction of glial fibrillary acidic protein (GFAP)-immunoreactivity in the rat dentate gyrus after adrenalectomy: comparison with neurodegenerative changes using silver impregnation, Hippocampus, 4 (1994) 307–314.

    PubMed  CAS  Google Scholar 

  235. Izumi, Y., Pinard, E., Roussel, S., and Seylaz, J., Insulin protects brain tissue against focal brain ischemia in rats, Neurosci. Lett., 144 (1992) 121–123.

    PubMed  CAS  Google Scholar 

  236. Hockenbery, D., Nunez, G., Milliman, C., Schreiber, R. D., and Korsmeyer, S. J., Bc1–2 is an inner mitochondrial membrane protein that blocks programmed cell death, Nature, 348 (1990) 334–336.

    PubMed  CAS  Google Scholar 

  237. Li, Y., Chopp, M., Jiang, N., Zhang, M. G., and Zalago, C., Induction of DNA fragmentation after 10 to 120 minutes of focal cerebral ischemia in rats, Stroke, 26 (1995) 1252–1258.

    Google Scholar 

Download references

Authors
  1. Gert J. Ter Horst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Postigo
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biological Psychiatry, Groningen Center for Behavioral and Cognitive Neurosciences, University of Groningen, The Netherlands

    Gert J. Ter Horst  & Jakob Korf  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ter Horst, G.J., Postigo, A. (1997). Stroke. In: Ter Horst, G.J., Korf, J. (eds) Clinical Pharmacology of Cerebral Ischemia. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-472-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-472-6_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4783-6

  • Online ISBN: 978-1-59259-472-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation