Neurochemical Research

, Volume 28, Issue 2, pp 293–305 | Cite as

Astrocytes and Stroke: Networking for Survival?

  • Michelle F. Anderson
  • Fredrik Blomstrand
  • Christian Blomstrand
  • P. S. Eriksson
  • Michael Nilsson

Abstract

Astrocytes are now known to be involved in the most integrated functions of the central nervous system. These functions are not only necessary for the normally working brain but are also critically involved in many pathological conditions, including stroke. Astrocytes may contribute to damage by propagating spreading depression or by sending proapoptotic signals to otherwise healthy tissue via gap junction channels. Astrocytes may also inhibit regeneration by participating in formation of the glial scar. On the other hand, astrocytes are important in neuronal antioxidant defense and secrete growth factors, which probably provide neuroprotection in the acute phase, as well as promoting neurogenesis and regeneration in the chronic phase after injury. A detailed understanding of the astrocytic response, as well as the timing and location of the changes, is necessary to develop effective treatment strategies for stroke patients.

Astrocytes ischemia stroke gap junctions spreading depression glutamate 

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REFERENCES

  1. 1.
    Ameriso, S. F. and Sahai, S. 1997. Mechanisms of ischemia in in situ vascular occlusive disease.Google Scholar
  2. 2.
    Pulsinelli, W. A., Jacewicz, M., Levy, D. E., Petito, C. K., and Plum, F. 1997. Ischemic brain injury and the therapeutic window. Ann. N. Y. Acad. Sci. 835:187–193.PubMedGoogle Scholar
  3. 3.
    Lipton, P. 1999. Ischemic cell death in brain neurons. Physiol. Rev. 79:1431–1568.PubMedGoogle Scholar
  4. 4.
    Legos, J. J. 2002. Pharmacological interventions for stroke: failures and future. Expert. Opin. Investig. Drugs 11:603–614.PubMedGoogle Scholar
  5. 5.
    Wardlaw, J. M., Warlow, C. P., and Counsell, C. 1997. Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke. Lancet 350:607–614.PubMedGoogle Scholar
  6. 6.
    Hacke, W., Kaste, M., Fieschi, C., von Kummer, R., Davalos, A., Meier, D., Larrue, V., Bluhmki, E., Davis, S., Donnan, G., Schneider, D., Diez-Tejedor, E., and Trouillas, P. 1998. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australian Acute Stroke Study Investigators Lancet 352:1245–1251.Google Scholar
  7. 7.
    Kaste, M., Thomanssen, L., Grond, M., Hacke, W., Holtåas, S., Lindley, R. I., Rone, R. O., Wahlgren, N. G., and Wardlaw, J. M. 2000. Thrombolysis for acute ischemic stroke: a consensus statement of the 3rd Karolinska stroke update. Stroke 32:2717–2718.Google Scholar
  8. 8.
    Ringleb, P. A., Schellinger, P. D., Schranz, C., and Hacke, W. 2002. Thrombolytic therapy with 3 to 6 hours after onset of ischemic stroke. Useful or harmful? Stroke 33:1437–1441.PubMedGoogle Scholar
  9. 9.
    Cochrane Database Syst. Rev 2002;(1):CD000197. Organised inpatient (stroke unit) care for stroke. Stroke Unit Trialists' Collaboration.Google Scholar
  10. 10.
    Hertz, L., Yu, A. C., Kala, G., and Schousboe, A. 2000. Neuronal-astrocytic and cytosolic-mitochondrial metabolite trafficking during brain activation, hyperammonemia and energy deprivation. Neurochem. Int. 37:83–102.PubMedGoogle Scholar
  11. 11.
    Araque, A., Carmignoto, G., and Haydon, P. G. 2001. Dynamic signalling between astrocytes and neurons. Annu. Rev. Physiol. 63:795–813.PubMedGoogle Scholar
  12. 12.
    Haydon, P. G. 2001. GLIA:listening and talking to the synapse. Nat. Rev. Neurosci. 2:185–193.PubMedGoogle Scholar
  13. 13.
    Kirchhoff, F., Dringen, R., and Giaume, C. 2001. Pathways of neuron-astrocyte interactions and their possible role in neuro-protection. Eur. Arch. Psychiatry Clin. Neurosci. 251:159–169.PubMedGoogle Scholar
  14. 14.
    Forsyth, R. J. 1996. Astrocytes and the delivery of glucose from plasma to neurons. Neurochem. Int. 28:231–241.PubMedGoogle Scholar
  15. 15.
    Nilsson M., Hansson, E., and Rönnbäck, L. 1991. Adrenergic and 5–HT2 receptors on the same astroglial cell: A microspectrofluorimetric study on cytosolic Ca2+ responses in single cells in primary culture. Brain Res. Dev. Brain Res. 63:33–41.PubMedGoogle Scholar
  16. 16.
    Nilsson M., Eriksson, P. S., Rönbbäck, L., and Hansson, E. 1993. GABA induces Ca2+ transients in astrocytes. Neuroscience 54:605–614.PubMedGoogle Scholar
  17. 17.
    Verkhratsky, A. and Kettenmann, H. 1996. Calcium signalling in glial cells. Trends Neurosci. 19:346–352.PubMedGoogle Scholar
  18. 18.
    Porter, J. T. and McCarthy, K. D. (1997) Astrocytic neurotransmitter receptors in situ and in vivo. Prog. Neurobiol. 51: 439–455.PubMedGoogle Scholar
  19. 19.
    Ventura, R. and Harris, K. M. 1999. Three-dimensional relationships between hippocampal synapses and astrocytes. J. Neurosci. 19:6897–6906.PubMedGoogle Scholar
  20. 20.
    Bezzi, P., Carmignoto, G., Pasti, L., Vesce, S., Rossi, D., Rizzini, B. L., Pozzan, T. and Volterra, A. 1998. Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 391:281–285.PubMedGoogle Scholar
  21. 21.
    Duffy, S. and MacVicar, B. A. 1995. Adrenergic calcium signaling in astrocyte networks within the hippocampal slice. J. Neurosci. 15:5535–5550.PubMedGoogle Scholar
  22. 22.
    Shelton, M. K. and McCarthy, K. D. 2000. Hippocampal astrocytes exhibit Ca2+-elevating muscarinic cholinergic and histaminergic receptors in situ. J. Neurochem. 74:555–563.PubMedGoogle Scholar
  23. 23.
    Kang, J., Jiang, L., Goldman, S. A., and Nedergaard, M. 1998. Astrocyte-mediated potentiation of inhibitory synaptic transmission. Nat. Neurosci. 1:683–692.PubMedGoogle Scholar
  24. 24.
    Parpura, V., Basarsky, T. A., Liu, F., Jeftinija, K., Jeftinija, S., and Haydon, P. G. 1994. Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747.PubMedGoogle Scholar
  25. 25.
    Muyderman, H., Angehagen, M., Sandberg, M., Bjorklund, U., Olsson, T., Hansson, E., and Nilsson, M. 2001. Alpha 1–adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes. J. Biol. Chem. 276:46504–46514.PubMedGoogle Scholar
  26. 26.
    Araque, A., Parpura, V., Sanzgiri, R. P., and Haydon, P. G. 1998. Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur. J. Neurosci. 10:2129–2142.PubMedGoogle Scholar
  27. 27.
    Rouach, N., Avignone, E., Meme, W., Koulakoff, A., Venance, L., Blomstrand, F., and Giaume, C. 2002. Gap junctions and connexin expression in the central nervous system. Biol. Cell. In press.Google Scholar
  28. 28.
    Tabernero, A., Giaume, C., and Medina, J. M. 1996. Endothelin-1 regulates glucose utilization in cultured astrocytes by controlling intercellular communication through gap junctions. Glia 16:187–195.PubMedGoogle Scholar
  29. 29.
    Charles, A. and Giaume, C. 2002. Intercellular calcium waves in astrocytes: underlying mechanisms and functional significance. Page 110–126, in Volterra, A., Haydon, P., and Magistretti, P. (eds), In Tripartite Synapses: Synaptic Transmission with Glia, Oxford University Press, London.Google Scholar
  30. 30.
    Enkvist, M. O. and McCarthy, K. D. 1994. Astroglial gap junction communication is increased by treatment with either glutamate or high K+ concentration. J. Neurochem. 62:489–495.PubMedGoogle Scholar
  31. 31.
    Blomstrand, F., Khatibi, S., Muyderman, H., Hansson, E., Olsson, T., and Ronnback, L. 1999. 5–Hydroxytryptamine and glutamate modulate velocity and extent of intercellular calcium signalling in hippocampal astroglial cells in primary cultures. Neuroscience 88:1241–1253.PubMedGoogle Scholar
  32. 32.
    Lipton, P. 1999. Ischemic cell death in brain neurons. 79: 1431–1568.Google Scholar
  33. 33.
    Folbergrová, J., Memezawa, H., Smith, M.-L., and Siesjö, B. K. 1992. Focal and perifocal changes in tissue energy state during middle cerebral artery occlusion in normo-and hyperglycemic rats. J. Cereb. Blood Flow Metab. 12:25–33.PubMedGoogle Scholar
  34. 34.
    Kuroda, S., Katsura, K.-I., Tsuchidate, R., and Siesjö, B. K. 1996. Secondary bioenergetic failure after transient focal ischemia is due to mitochondrial injury. Acta Physiol. Scand. 156:149–150.PubMedGoogle Scholar
  35. 35.
    Anderson, M. F. and Sims, N. R. 1999. Mitochondrial respiratory function and cell death in focal cerebral ischaemia. J. Neurochem. 73:1189–1199.PubMedGoogle Scholar
  36. 36.
    Sims, N. R. and Zaidan, E. 1995. Biochemical changes associated with selective neuronal death following short-term cerebral ischemia. Int. J. Biochem. Cell Biol. 27:531–550.PubMedGoogle Scholar
  37. 37.
    Hossmann, K.-A. 1994. Viability thresholds and the penumbra of focal ischemia. Ann. Neurol. 36:557–565.PubMedGoogle Scholar
  38. 38.
    Kaplan, B., Brint, S., Tanabe, J., Jacewicz, M., Wang, X.-J., and Pulsinelli, W. A. 1991. Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. Stroke 22:1032–1039.PubMedGoogle Scholar
  39. 39.
    Buchan, A. M., Xue, D., and Slivka, A. 1992. A new model of temporary focal neocortical ischemia in the rat. Stroke 23: 273–279.PubMedGoogle Scholar
  40. 40.
    Memezawa, H., Smith, M.-L., and Siesjö, B. K. 1992. Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats. Stroke 23:552–559.PubMedGoogle Scholar
  41. 41.
    Garcia, J. H., Liu, K.-F., and Ho, K.-L. 1995. Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26:636–642.PubMedGoogle Scholar
  42. 42.
    Li, Y., Chopp, M., Jiang, N., Zhang, Z. G., and Zaloga, C. 1995. Induction of DNA fragmentation after 10 to 120 minutes of focal cerebral ischemia in rats. Stroke 26:1252–1257.PubMedGoogle Scholar
  43. 43.
    Markgraf, C. G., Velayo, N. L., Johnson, M. P., McCarty, D. R., Medhi, S., Koehl, J. R., Chmielewski, P. A., and Linnik, M. D. 1998. Six-hour window of opportunity for calpain inhibition in focal cerebral ischemia in rats. Stroke 29:152–158.PubMedGoogle Scholar
  44. 44.
    Yoshimoto, T. and Siesjö, B. K. 1999. Posttreatment with the immunosuppressant cyclosporin A in transient focal ischemia. Brain Res. 839:283–291.PubMedGoogle Scholar
  45. 45.
    Marrif, H. and Juurlink, B. H. 1999. Astrocytes respond to hypoxia by increasing glycolytic capacity. J. Neurosci. Res. 57: 255–260.PubMedGoogle Scholar
  46. 46.
    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.PubMedGoogle Scholar
  47. 47.
    Liu, D., Smith, C. L., Barone, F. C., Ellison, J. A., Lysko, P. G., Li, K., and Simpson, I. A. 1999. Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain. Mol. Brain Res. 68:29–41.PubMedGoogle Scholar
  48. 48.
    Hagberg, A., Qu, H., Saether, O., Unsgard, G., Haraldseth, O., and Sonnewald, U. 2001. Differences in neurotransmitter synthesis and intermediary metabolism between glutamatergic and GABAergic neurons during 4 hours of middle cerebral artery occlusion in the rat: The role of astrocytes in neuronal survival. J. Cereb. Blood Flow Metab. 21:1451–1463.PubMedGoogle Scholar
  49. 49.
    Kimelberg, H. K., Goderie, S. K., Higman, S., Pang, S., and Waniewski, R. A. 1990. Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures. J. Neurosci. 10: 1583–1591.PubMedGoogle Scholar
  50. 50.
    Landis, D. M. 1994. The early reactions of non-neuronal cells to brain injury. Annu. Rev. Neurosci. 17:133–151.PubMedGoogle Scholar
  51. 51.
    Aschner, M. 1998. Astrocytic functions and physiological reactions to injury: the potential to induce and/or exacerbate neuronal dysfunction—a forum position paper. Neurotoxicology 19:7–17.PubMedGoogle Scholar
  52. 52.
    Kimelberg, H. C. 2000. Cell volume in the CNS: Regulation and implication for central nervous system pathology. Neuroscientist 6:13–24.Google Scholar
  53. 53.
    Syková, E. 2001. Glial diffusion barriers during aging and pathological states. Prog. Brain Res. 132:339–363.PubMedGoogle Scholar
  54. 54.
    Ayata, C. and Ropper, A. H. 2002. Ischemic brain oedema. J. Clin. Neurosci. 9:113–124.PubMedGoogle Scholar
  55. 55.
    Syková, E. 1997. The extracellular space in the CNS: its regulation, volume and geometry in normal and pathological neuronal function. Neuroscientist 3:28–41.Google Scholar
  56. 56.
    Takahashi, K., Greenberg, J. H., Jackson, P., Maclin, K., and Zhang, J. 1997. Neuroprotective effects of inhibiting poly(ADP-ribose) synthetase on focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 17:1137–1142.PubMedGoogle Scholar
  57. 57.
    Hudspith, M. J. 1997. Glutamate: a role in normal brain function, anaesthesia, analgesia and CNS injury. Br. J. Anaesth. 78:731–747.PubMedGoogle Scholar
  58. 58.
    Guthrie, P. B., Knappenberger, J., Segal, M., Bennett, M. V., Charles, A. C., and Kater, S. B. 1999. ATP released from astrocytes mediates glial calcium waves. J. Neurosci. 19:520–528.PubMedGoogle Scholar
  59. 59.
    Innocenti, B., Parpura, V., and Haydon, P. G. 2000. Imaging extracellular waves of glutamate during calcium signaling in cultured astrocytes. J. Neurosci. 20:1800–1808.PubMedGoogle Scholar
  60. 60.
    Martínez, A. D. and Sáez, J. C. 2000. Regulation of astrocytes gap junctions by hypoxia-reoxygenation. Brain Res. Rev. 32:250–258.PubMedGoogle Scholar
  61. 61.
    Cotrina, M. L., Kang, J., Lin, J. H., Bueno, E., Hansen, T. W., He, L., Liu, Y., and Nedergaard M. 1998. Astrocytic gap junctions remain open during ischemic conditions. J. Neurosci. 18:2520–2537.PubMedGoogle Scholar
  62. 62.
    Lin, J. H., Weigel, H., Cotrina, M. L., Liu, S., Bueno, E., Hansen, A. J., Hansen, T. W., Goldman, S., and Nedergaard, M. 1998. Gap-junction-mediated propagation and amplification of cell injury. Nat. Neurosci. 1:494–500.PubMedGoogle Scholar
  63. 63.
    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.PubMedGoogle Scholar
  64. 64.
    Li, Y., Chopp, M., Jiang, N., and Zaloga, C. 1995. In situ detection of DNA fragmentation after focal cerebral ischemia in mice. Mol. Brain Res. 28:164–168.PubMedGoogle Scholar
  65. 65.
    Budd, S. L. and Lipton, S. A. 1998. Calcium tsunamis: do astrocytes transmit cell death messages via gap junctions during ischemia? Nat. Neurosci. 1:431–432.PubMedGoogle Scholar
  66. 66.
    Rami, A., Volkmann, T., and Winckler, J. 2001. Effective reduction of neuronal death by inhibiting gap junctional intercellular communication in a rodent model of global transient cerebral ischemia. Exp. Neurol. 170:297–304.PubMedGoogle Scholar
  67. 67.
    Rawanduzy, A., Hansen, A., Hansen, T. W., and Nedergaard, M. 1997. Effective reduction of infarct volume by gap junction blockade in a rodent model of stroke. J. Neurosurg. 87:916–920.PubMedGoogle Scholar
  68. 68.
    Saito, R., Graf, R., Hubel, K., Fujita, T., Rosner, G., and Heiss, W. D. 1997. Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarisations. J. Cereb. Blood Flow Metab. 17:857–864.PubMedGoogle Scholar
  69. 69.
    Siushansian, R., Bechberger, J. F., Cechetto, D. F., Hachinski, V. C., and Naus, C. C. 2001. Connexin43 null mutation increases infarct size after stroke. J. Comp. Neurol. 440:387–394.PubMedGoogle Scholar
  70. 70.
    Blanc, E. M., Bruce-Keller, A. J., and Mattson, M. P. 1998. Astrocytic gap junction communication decreases neuronal vulnerability to oxidative stress-induced disruption of Ca2+ homeostasis and cell death. J. Neurochem. 70:958–970.PubMedGoogle Scholar
  71. 71.
    Nedergaard, M. and Astrup, J. 1986. Infarct rim: effect of hyperglycemia on direct current potential and [14C]2–deoxyglucose phosphorylation. J. Cereb. Blood Flow Metab. 6:607–615.PubMedGoogle Scholar
  72. 72.
    Gill, R., Nordholm, L., and Lodge, D. 1992. The neuroprotective actions of 2,3–dihydroxy-6–nitro-7–sulfamoyl-benzo(F)quinozaline (NBQX) in a rat focal ischaemic model. Brain Res. 580: 35–43.PubMedGoogle Scholar
  73. 73.
    Nedergaard, M. and Hansen, A. J. 1998. Spreading depression is not associated with neuronal injury in the normal brain. Brain Res. 449:395–398.Google Scholar
  74. 74.
    Iijima, T., Mies, G., and Hossmann, K. A. 1992. Repeated negative DC deflections in rat cortex following middle cerebral artery occlusion are abolished by MK-801: effect on volume of ischemic injury. J. Cereb. Blood Flow Metab. 12:727–733.PubMedGoogle Scholar
  75. 75.
    Chen, Q., Chopp, M., Bodzin, G., and Chen, H. 1993. Temperature modulation of cerebral depolarization during focal cerebral ischemia in rats: Correlation with ischemic injury. J. Cereb. Blood Flow Metab. 13:389–394.PubMedGoogle Scholar
  76. 76.
    Mies, G. 1993. Inhibition of protein synthesis during repetitive cortical spreading depression. J. Neurochem. 60:360–363.PubMedGoogle Scholar
  77. 77.
    Busch, E., Gyngell, M. L., Eis, M., Hoehn-Berlage, M., and Hossmann, K. A. 1996. Potassium-induced cortical spreading depressions during focal cerebral ischemia in rats: contribution to lesion growth assessed by diffusion-weighted NMR and biochemical imaging. J. Cereb. Blood Flow Metab. 16:1090–1099.PubMedGoogle Scholar
  78. 78.
    Takano, K., Latour, L. L., Formato, J. E., Carano, R. A., Helmer, K. G., Hasegawa, Y., Sotak, C. H., and Fisher, M. 1996. The role of spreading depression in focal ischemia evaluated by diffusion mapping. Ann. Neurol. 39:308–318.PubMedGoogle Scholar
  79. 79.
    Martins-Ferreira, H., Nedergaard, M., and Nicholson, C. 2000. Perspectives on spreading depression. Brain Res. Rev. 32:215–234.PubMedGoogle Scholar
  80. 80.
    Basarsky, T. A., Duffy, S. N., Andrew, R. D., and MacVicar, B. A. 1998. Imaging spreading depression and associated intracellular calcium waves in brain slices. J. Neurosci. 18: 7189–7199.PubMedGoogle Scholar
  81. 81.
    Kunkler, P. E. and Kraig, R. P. 1998. Calcium waves preceed electrophysiological changes of spreading depression in hippocampal cultures. J. Neurosci. 18:3416–3425.PubMedGoogle Scholar
  82. 82.
    Sugaya, E., Takato, M., and Noda, Y. 1975. Neuronal and glial activity during spreading depression in cerebral cortex of cat. J. Neurophysiol. 38:822–841.PubMedGoogle Scholar
  83. 83.
    Largo, C., Cuevas, P., and Herreras, O. 1996. Is glia disfunction the initial cause of neuronal death in ischemic penumbra? Neurol. Res. 18:445–448.PubMedGoogle Scholar
  84. 84.
    Floyd, R. A. 1999. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc. Soc. Exp. Biol. Med. 222:236–245.PubMedGoogle Scholar
  85. 85.
    Bains, J. S. and Shaw, C. A. 1997. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res. Rev. 25:335–358.PubMedGoogle Scholar
  86. 86.
    Schulz, J. B., Lindenau, J., Seyfried, J., and Dichgans, J. 2000. Glutathione, oxidative stress and neurodegeneration Eur. J. Biochem. 267:4904–4911.PubMedGoogle Scholar
  87. 87.
    Chan, P. H. 1996. Role of oxidants in ischemic brain damage. Stroke 27:1124–1129.PubMedGoogle Scholar
  88. 88.
    Piantadosi, C. A. and Zhang, J. 1996. Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. Stroke 27:327–331.PubMedGoogle Scholar
  89. 89.
    Kuroda, S. and Siesjö, B. K. 1997. Reperfusion damage following focal ischemia: pathophysiology and therapeutic windows. Clin. Neurosci. 4:199–212.PubMedGoogle Scholar
  90. 90.
    Nowicki, J. P., Duval, D., Poignet, H., and Scatton, B. 1991. Nitric oxide mediates neuronal death after focal cerebral ischemia in the mouse. Eur. J. Pharmacol. 204:339–340.PubMedGoogle Scholar
  91. 91.
    Ranjan, A., Theodore, D., Haran, R. P., and Chandy, M. J. 1993. Ascorbic acid and focal cerebral ischaemia in a primate model. Acta Neurochir. (Wien.) 123:87–91.Google Scholar
  92. 92.
    Dawson, D. A., Graham, D. I., McCulloch, J., and Macrae, I. M. 1994. Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-D-aspartate receptor antagonist in models of transient and permanent focal cerebral ischaemia. Br. J. Pharmacol. 113:247–253.PubMedGoogle Scholar
  93. 93.
    Baker, K., Marcus, C. B., Huffman, K., Kruk, H., Malfroy, B., and Doctrow, S. R. 1998. Synthetic combined superoxide dismutase catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury. J. Pharm. Exp. Ther. 284:215–221.Google Scholar
  94. 94.
    Fukuyama, N., Takizawa, S., Ishida, H., Hoshiai, K, Shinohara, Y., and Nakazawa, H. 1998. Peroxynitrite formation in focal cerebral ischemia-reperfusion in rats occurs predominantly in the peri-infarct region. J. Cerebr. Blood Flow Metab. 18:123–129.Google Scholar
  95. 95.
    Heales, S. J. R., Bolaños, J. P., Stewart V. C., Brookes, P. S., Land, J. M., and Clark, J. B. 1999. Nitric oxide, mitochondria and neurological disease. Biochim. Biophys. Acta 1410:215–228.PubMedGoogle Scholar
  96. 96.
    Dringen, R. 2000. Metabolism and functions of glutathione in brain. Prog. Neurobiol. 62:649–671.PubMedGoogle Scholar
  97. 97.
    Dringen, R., Pfeiffer, B., and Hamprecht, B. 2002. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J. Neurosci. 19:562–569.Google Scholar
  98. 98.
    Iwata-Ichikawa, E., Kondo, Y., Miyazaki, I., Asanuma, M., and Ogawa, N. 1999. Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis. J. Neurochem. 72:2334–2344.PubMedGoogle Scholar
  99. 99.
    Chen, Y., Vartiainen, N. E., Ying, W., Chan, P. H., Koistinaho, J., and Swanson, R. A. 2001. Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism. J. Neurochem. 77:1601–1610.PubMedGoogle Scholar
  100. 100.
    Wallin, C., Puka-Sundvall, M., Hagberg, H., Weber, S. G., and Sandberg, M. 2000. Alterations in glutathione and amino acid concentrations after hypoxia-ischemia in the immature rat brain. Dev. Brain Res. 125:51–60.Google Scholar
  101. 101.
    Uemura, Y., Miller, J. M., Matson, W. R., and Beal, M. F. 1991. Neurochemical analysis of focal ischemia in rats. Stroke 22: 1548–1553.PubMedGoogle Scholar
  102. 102.
    Gotoh, O., Yamamoto, M., Tamura, A., and Sano, K. 1994. Effect of YM737, a new glutathione analogue, on ischemic brain edema. Acta Neurochir. Suppl. 60, 318–320.Google Scholar
  103. 103.
    Anderson, M. F. and Sims, N. R. 2002. The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions. J. Neurochem. 81:541–549.PubMedGoogle Scholar
  104. 104.
    Mizui, T., Kinouchi, H., and Chan, P. H. 1992. Depletion of brain glutathione by buthionine sulfoximine enhances cerebral ischemic injury in rats. Am. J. Physiol. 262:H313–H317.PubMedGoogle Scholar
  105. 105.
    Fernández-Checa, J. C., García-Ruiz, C., Ookhtens, M., and Kaplowitz, N. 1991. Impaired uptake of glutathione by hepatic mitochondria from chronic ethanol-fed rats. Tracer kinetic studies in vitro and in vivo and susceptibility to oxidant stress. J. Clin. Invest. 87:397–405.PubMedGoogle Scholar
  106. 106.
    García-Ruiz, C., Morales, A., Ballesta, A., Rodes, J., Kaplowitz, N., and Fernández-Checa, J. C. 1994. Effect of chronic ethanol feeding on glutathione and functional integrity of mitochondria in periportal and perivenous rat hepatocytes. J. Clin. Invest. 94:193–201.PubMedGoogle Scholar
  107. 107.
    Collel, A., García-Ruiz, C., Miranda, M., Ardite, E., Mári, M., Morales, A., Corrales, F., Kaplowitz, N., and Fernández-Checa, J. C. 1998. Selective glutathione depletion of mitochondria by ethanol sensitises hepatocytes to tumour necrosis factor. Gastroenterology 115:1541–1551.PubMedGoogle Scholar
  108. 108.
    Wüllner, U., Seyfried, J., Groscurth, P., Beinroth, S., Gleichmann, M., Heneka, M., Löschmann, P. A., Schulz, J. B., Weller, M., and Klockgether, T. 1999. Glutathione depletion and neuronal cell death: the role of reactive oxygen intermediates and mitochondrial function. Brain Res. 826:53–62.PubMedGoogle Scholar
  109. 109.
    Schallert, T., Leasure, J. L., and Kolb, B. 2000. Experience-associated structural events, subependymal cellular proliferative activity, and functional recovery after injury to the central nervous system. J. Cereb. Blood Flow Metab. 20:1513–1528.PubMedGoogle Scholar
  110. 110.
    Dahlqvist, P., Zhao, L., Johansson, I. M., Mattsson, B., Johansson, B. B., Seckl, J. R., and Olsson, T. 1999. Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats. Neuroscience 93:527–535.PubMedGoogle Scholar
  111. 111.
    Liepert, J., Bauder, H., Miltner, W. H. R., Taub, E., and Weiller, C. 2000. Treatment-induced cortical reorganization after stroke in humans. Stroke 31:1210–1216.PubMedGoogle Scholar
  112. 112.
    Johansson, B. B. and Belichenko, P. V. 2002. Neuronal plasticity and dentritic spines: effect of environmental enrichment on intact and postischemic rat brain. J. Cereb. Blood Flow Metab. 22:89–96.PubMedGoogle Scholar
  113. 113.
    Komitova, M., Perfilieva, E., Mattsson, B., Eriksson, P. S., and Johansson, B. B. 2002. Effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis and differentiation in the adult rat. J. Cereb. Blood Flow Metab. 22:852–860.PubMedGoogle Scholar
  114. 114.
    Ridet, J. L., Malhotra, S. K., Privat, A., and Gage, F. H. 1997. Reactive astrocytes: cellular and molecular cues to biological functions. Trends Neurosci. 20:570–577.PubMedGoogle Scholar
  115. 115.
    Little, A. R. and O'Callaghan, J. P. 2001. Astrogliosis in the adult and developing CNS: is there are role for proinflammatory cytokines. NeuroToxicology 22:607–618.PubMedGoogle Scholar
  116. 116.
    Clarke, S. R., Shetty, A. K., Bradley, J. L., and Turner, D. A. 1994. Reactive astrocytes express the embryonic intermediate neurofilament nestin. Neuroreport 5:1885–1888.PubMedGoogle Scholar
  117. 117.
    Eng, L. F. and Ghirnikar, R. S. 1994. GFAP and astrogliosis. Brain Pathol. 4:229–237.PubMedGoogle Scholar
  118. 118.
    Holmin, S., Almqvist, P., Lendahl, U., and Mathiesen, T. 1997. Adult nestin-expressing subependymal cells differentiate to astrocytes in response to brain injury. Eur. J. Neurosci. 9:65–75.PubMedGoogle Scholar
  119. 119.
    Pixley, S. K. and De Vellis, J. 1984. Transition between radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Brain Res. 15:201–209.Google Scholar
  120. 120.
    Lendahl, V., Zimmerman, L. B., and McKay, R. D. G. 1990. CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595.PubMedGoogle Scholar
  121. 121.
    Sancho-Tello, M., Vallés, S., Montoliu, C., Renau-Piqueras, J., and Guerri, C. 1995. Developmental pattern of GFAP and vimentin expression in rat brain and radial glial cultures. Glia 15:157–166.PubMedGoogle Scholar
  122. 122.
    Kajihara, H., Tsutsumi, E., Kinoshita, A., Nakano, J., Takagi, K., and Takeo, S. 2001. Activated astrocytes with glycogen accumulation in ischemic penumbra during the early stage of brain infarction: immunohistochemical and electron microscopic studies. Brain Res. 909:92–101.PubMedGoogle Scholar
  123. 123.
    Cramer, S. C. and Chopp, M. 2000. Recovery recapitulates ontogeny. Trends Neurosci. 23:265–271.PubMedGoogle Scholar
  124. 124.
    Luskin, M. B. 1993. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain sub-ventricular zone. Neuron 11:173–189.PubMedGoogle Scholar
  125. 125.
    Lois, C. and Alvarez-Buylla, A. 1994. Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148.PubMedGoogle Scholar
  126. 126.
    Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A.-M., Nordborg C., and Gage, F. H. 1998. Neurogenesis in the adult human hippocampus. Nature Med. 11:1313–1317.Google Scholar
  127. 127.
    Arvidsson, A., Kokaia, Z., and Lindvall, O. 2001. N-Methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke. Eur. J. Neurosci. 14:10–18.PubMedGoogle Scholar
  128. 128.
    Jiang, W., Gu, W., Brännström, T., Rosqvist R., and Wester, P. 2001. Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion. Stroke 32:1201–1207.PubMedGoogle Scholar
  129. 129.
    Jin, K, Minami, M., Lan, J. Q., Mao, X. O., Batteur, S., Simon, R. P., and Greenberg, D. A. 2001. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc. Natl. Acad. Sci. USA 98: 4710–4715.PubMedGoogle Scholar
  130. 130.
    Kee, N. J., Preston, E., and Wojtowicz, J. M. 2001. Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. Exp. Brain Res. 136:313–320.PubMedGoogle Scholar
  131. 131.
    Zhang, R. L., Zhang, Z. G., Zhang, L., and Chopp, M. 2001. Proliferation and differentiation of progenitor cells in the cortex and subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience 105:33–41.PubMedGoogle Scholar
  132. 132.
    Palmer, T. D., Markakis, E. A., Willhoite, A. R., Safar, F., and Gage, F. H. 1999. Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cell from diverse regions of adult CNS. J. Neurosci. 19:8487–8497.PubMedGoogle Scholar
  133. 133.
    Palmer, T. D., Ray, J., and Gage, F. H. 1995. Fibroblast growth factor-2 responsive neuronal progenitors reside in proliferating and quiescent regions of the adult rodent brain. Mol. Cell. Neurosci. 6:474–486.PubMedGoogle Scholar
  134. 134.
    Gu, W., Brännström, T., and Wester, P. 2000. Cortical neurogenesis in adult rats after reversible photothrombotic stroke. J. Cereb. Blood Flow Metab. 20:1166–1173.PubMedGoogle Scholar
  135. 135.
    Kuhn, H. G., Winkler, J., Kempermann, G., Thal, L. J., and Gage, F. H. 1997. Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J. Neurosci. 17:5820–5829.PubMedGoogle Scholar
  136. 136.
    Åberg, A. I., Åberg, D., Hedbäcker, H., Oscarsson, J., and Eriksson, P. S. 2000. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J. Neurosci. 20:2896–2903.PubMedGoogle Scholar
  137. 137.
    Lim, D. A. and Alvarez-Buylla, A. 1999. Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proc. Natl. Acad. Sci. USA 96:7526–7531.PubMedGoogle Scholar
  138. 138.
    Song, H.-J., Stevens, C. F., and Gage, F. H. 2002. Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nature Neurosci. 5:438–445.PubMedGoogle Scholar
  139. 139.
    Alonso, G. 2001. Proliferation of progenitor cells in the adult rat brain correlates with the presence of vimentin-expressing astrocytes. Glia 34:253–266.PubMedGoogle Scholar
  140. 140.
    Song, H., Stevens, C. F., and Gage, F. H. 2002. Astroglia induce neurogenesis from adult neural stem cells. Nature 417:39–44.PubMedGoogle Scholar
  141. 141.
    Doetsch, F., García-Verdugo, J. M., and Alvarez-Buylla, A. 1997. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17:5046–5061.PubMedGoogle Scholar
  142. 142.
    Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. 1999. Subventricular zone astrocytes are neuronal stem cells in the adult mammalian brian. Cell 97:703–716.PubMedGoogle Scholar
  143. 143.
    Seri, B., García-Verdugo, J. M., McEwen, B. S., and Alvarez-Buylla, A. 2001. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J. Neurosci. 21:7153–7160.PubMedGoogle Scholar
  144. 144.
    Alvarez-Buylla, A., Seri, B., and Doetsch, F. 2002. Identification of neural stem cells in the adult vertebrate brain. Brain Res. Rev. 57:751–758.Google Scholar
  145. 145.
    Åberg, M. A. I., Hellgren, G., Lindell, K., Rosengren, L., MacLennan, A. J., Carlsson, B., and Eriksson, P. S. 2001. CNTF induces gliogenesis via the JAK-STAT-Tis11 signaling pathway in adult CNS progenitor cells. Mol. Cell Neurosci. 17: 426–443.PubMedGoogle Scholar
  146. 146.
    Lin, T.-N., Wang, P. Y., Chi, S. I., and Kuo, J. S. 1998. Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFR alpha) expression following focal cerebral ischemia. Mol. Brain Res. 55:71–80.PubMedGoogle Scholar
  147. 147.
    Fawcett, J. W. and Asher R. A. 1999. The glial scar and central nervous system repair. Brain Res. Bull. 49:377–391.PubMedGoogle Scholar
  148. 148.
    McGraw, J., Hiebert, G. W., and Steeves, J. D. 2001. Modulating astrogliosis after neurotrauma. J. Neurosci. Res. 63: 109–115.PubMedGoogle Scholar
  149. 149.
    Pekny, M., Johansson, C. B., Eliasson, C., Stakeberg, J., Wallen, A., Perlmann, T., Lendahl, U., Betsholtz, C., Berthold, C. H., and Frisen, J. 1999. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145:503–514.PubMedGoogle Scholar
  150. 150.
    Menet, V., Gimenez, Y. R., Sandillon, F., and Privat, A. 2000. GFAP null astrocytes are a favourable substrate for neuronal survival and neurite growth. Glia 31:267–272.PubMedGoogle Scholar
  151. 151.
    Costa, S., Planchenault, T., Charriere-Bertrand, C., Mouchel, Y., Fages, C., Juliano, S., Lefrancois, T., Barlovatz-Meimon, G., and Tardy, M. 2002. Astroglial permissivity for neurite outgrowth in neuron-astrocyte cocultures depends on regulation of laminin bioavailability. Glia 37:105–113.PubMedGoogle Scholar
  152. 152.
    Hamberger, A. and Hyden, H. 1963. Inverse enzymatic changes in neurons and glia during increased function and hypoxia. J. Cell Biol. 6:521–525.Google Scholar
  153. 153.
    Blomstrand, C., Hallen, O., Hamberger, A., and Jarlstedt, J. 1966. Quantitative cytochemical aspects on the mechanism of central compensation after unilateral vestibular neurotomy. Acta Otolaryngol. 61:113–120.PubMedGoogle Scholar
  154. 154.
    Blomstrand, C., Hallen, O., Hamberger, A., and Jarlstedt, J. 1966. Effects of unilateral warm and cold water irrigation in the outer ear of rabbits on isolated nerve cells from the lateral vestibular nucleus and cerebellum. Acta Otolaryngol. 61:527–535.PubMedGoogle Scholar
  155. 155.
    Blomstrand, C., Hallen, O., Hamberger, A., and Jarlstedt, J. 1970. Effect of cerebellectomy upon the cytochemistry of neurons in the lateral vestibular nucleus 3. Cytochemical response to unilateral vestibular stimulation after midline section of the brain stem. Brain Res. 19:427–432.PubMedGoogle Scholar
  156. 156.
    Blomstrand, C. and Hamberger, A. 1969. Protein turnover in cell-enriched fractions from rabbit brain. J. Neurochem. 16:1401–1407.PubMedGoogle Scholar
  157. 157.
    Blomstrand, C. and Hamberger, A. 1970. Amino acid incorporation in vitro into protein of neuronal and glial cell-enriched fractions. J. Neurochem. 17:1187–1195.PubMedGoogle Scholar
  158. 158.
    Henn, F. A. and Hamberger, A. 1971. Glial cell function: uptake of transmitter substances. Proc Natl. Acad. Sci. USA 68:2686–2690.PubMedGoogle Scholar
  159. 159.
    Blomstrand, C. 1970. Effect of hypoxia on protein metabolism in neuron-and neuroglia cell-enriched fractions from rabbit brain. Exp. Neurol. 29:175–188.PubMedGoogle Scholar
  160. 160.
    Cochrane Database Syst. Rev 2002;(1):CD000197. Organised inpatient (stroke unit) care for stroke. Stroke Unit Trialists' Collaboration.Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Michelle F. Anderson
    • 1
  • Fredrik Blomstrand
    • 1
  • Christian Blomstrand
    • 1
  • P. S. Eriksson
    • 1
  • Michael Nilsson
    • 1
  1. 1.Institute of Clinical NeuroscienceGöteborg UniversityGöteborgSweden

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