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Experimental Platforms for Assessing White Matter Pathophysiology in Stroke

  • Ken Arai
  • Loc-Duyen D. Pham
  • Eng H. Lo
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

This chapter aims at summarizing current knowledge on experimental systems for analyzing the role of white matter injury relevant to stroke. In this chapter, we will provide a broad but brief survey of existing models at the cell, tissue, and whole-animal levels. Experimental approaches have recently allowed a better understanding of the molecular and cellular pathways underlying oligodendrocyte and oligodendrocyte precursor cell damage and demyelination. Since white matter damage is a clinically important part of stroke, a systematic utilization of these cell/tissue/whole-animal platforms related to white matter pathophysiology may eventually lead us to discover new targets for treating stroke.

Keywords

White Matter Middle Cerebral Artery Occlusion White Matter Lesion White Matter Injury White Matter Damage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments and Funding

Supported in part by the National Institutes of Health, the American Heart Association, and the Deane Institute. Material including adapted figures for this chapter has been extensively drawn from previously published reviews including: Lo et al., Nat Rev Neurosci 2003; Lo, Nat Med 2008; Arai et al., FEBS J 2009; Arai and Lo, Exp Transl Stroke Med 2009; Arai and Lo, FEBS J 2009.

References

  1. 1.
    Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7(1):41–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Alberdi E, Sanchez-Gomez MV, Torre I, Domercq M, Perez-Samartin A, Perez-Cerda F, Matute C. Activation of kainate receptors sensitizes oligodendrocytes to complement attack. J Neurosci. 2006;26(12):3220–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Albrecht PJ, Enterline JC, Cromer J, Levison SW. CNTF-activated astrocytes release a soluble trophic activity for oligodendrocyte progenitors. Neurochem Res. 2007;32(2):263–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Alix JJ. Recent biochemical advances in white matter ischaemia. Eur Neurol. 2006;56(2):74–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Arai K, Lo EH. Astrocytes protect oligodendrocyte precursor cells via MEK/ERK and PI3K/Akt signaling. J Neurosci Res. 2010;88(4):758–63.PubMedCrossRefGoogle Scholar
  6. 6.
    Arai K, Lo EH. An oligovascular niche: cerebral endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells. J Neurosci. 2009;29(14):4351–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8:963–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Asahi M, Wang X, Mori T, Sumii T, Jung JC, Moskowitz MA, Fini ME, Lo EH. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood–brain barrier and white matter components after cerebral ischemia. J Neurosci. 2001;21(19):7724–32.PubMedGoogle Scholar
  9. 9.
    Bakiri Y, Hamilton NB, Karadottir R, Attwell D. Testing NMDA receptor block as a therapeutic strategy for reducing ischaemic damage to CNS white matter. Glia. 2008;56(2):233–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Baltan S. Ischemic injury to white matter: an age-dependent process. Neuroscientist. 2009;15(2):126–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Baltan S, Besancon EF, Mbow B, Ye Z, Hamner MA, Ransom BR. White matter vulnerability to ischemic injury increases with age because of enhanced excitotoxicity. J Neurosci. 2008;28(6):1479–89.PubMedCrossRefGoogle Scholar
  12. 12.
    Barres BA, Hart IK, Coles HS, Burne JF, Voyvodic JT, Richardson WD, Raff MC. Cell death and control of cell survival in the oligodendrocyte lineage. Cell. 1992;70(1):31–46.PubMedCrossRefGoogle Scholar
  13. 13.
    Bartlett WP, Knapp PE, Skoff RP. Glial conditioned medium enables jimpy oligodendrocytes to express properties of normal oligodendrocytes: production of myelin antigens and membranes. Glia. 1988;1(4):253–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S, Gallo V. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol. 2003;161(1):169–86.PubMedCrossRefGoogle Scholar
  15. 15.
    Bernstein SL, Guo Y, Kelman SE, Flower RW, Johnson MA. Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2003;44(10):4153–62.PubMedCrossRefGoogle Scholar
  16. 16.
    Butt AM, Ibrahim M, Ruge FM, Berry M. Biochemical subtypes of oligodendrocyte in the anterior medullary velum of the rat as revealed by the monoclonal antibody. Rip. Glia. 1995;14(3):185–97.PubMedCrossRefGoogle Scholar
  17. 17.
    Butts BD, Houde C, Mehmet H. Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease. Cell Death Differ. 2008;15(7):1178–86.PubMedCrossRefGoogle Scholar
  18. 18.
    Carty ML, Wixey JA, Colditz PB, Buller KM. Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens. Int J Dev Neurosci. 2008;26(5):477–85.PubMedCrossRefGoogle Scholar
  19. 19.
    Chandler S, Coates R, Gearing A, Lury J, Wells G, Bone E. Matrix metalloproteinases degrade myelin basic protein. Neurosci Lett. 1995;201(3):223–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Chang A, Nishiyama A, Peterson J, Prineas J, Trapp BD. NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J Neurosci. 2000;20(17):6404–12.PubMedGoogle Scholar
  21. 21.
    Choi DW. Ionic dependence of glutamate neurotoxicity. J Neurosci. 1987;7(2):369–79.PubMedGoogle Scholar
  22. 22.
    Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988;1(8):623–34.PubMedCrossRefGoogle Scholar
  23. 23.
    Choi DW. Cerebral hypoxia: some new approaches and unanswered questions. J Neurosci. 1990;10(8):2493–501.PubMedGoogle Scholar
  24. 24.
    Chopp M, Zhang ZG, Jiang Q. Neurogenesis, angiogenesis, and MRI indices of functional recovery from stroke. Stroke. 2007;38(2 Suppl):827–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Cioffi GA, Orgul S, Onda E, Bacon DR, Van Buskirk EM. An in vivo model of chronic optic nerve ischemia: the dose-dependent effects of endothelin-1 on the optic nerve microvasculature. Curr Eye Res. 1995;14(12):1147–53.PubMedCrossRefGoogle Scholar
  26. 26.
    Corley SM, Ladiwala U, Besson A, Yong VW. Astrocytes attenuate oligodendrocyte death in vitro through an alpha(6) integrin-laminin-dependent mechanism. Glia. 2001;36(3):281–94.PubMedCrossRefGoogle Scholar
  27. 27.
    Cui QL, Almazan G. IGF-I-induced oligodendrocyte progenitor proliferation requires PI3K/Akt, MEK/ERK, and Src-like tyrosine kinases. J Neurochem. 2007;100(6):1480–93.PubMedGoogle Scholar
  28. 28.
    Cui QL, Zheng WH, Quirion R, Almazan G. Inhibition of Src-like kinases reveals Akt-dependent and -independent pathways in insulin-like growth factor I-mediated oligodendrocyte progenitor survival. J Biol Chem. 2005;280(10):8918–28.PubMedCrossRefGoogle Scholar
  29. 29.
    del Zoppo GJ. Stroke and neurovascular protection. N Engl J Med. 2006;354(6):553–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Deng W, Rosenberg PA, Volpe JJ, Jensen FE. Calcium-permeable AMPA/kainate receptors mediate toxicity and preconditioning by oxygen-glucose deprivation in oligodendrocyte precursors. Proc Natl Acad Sci U S A. 2003;100(11):6801–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Dewar D, Dawson DA. Changes of cytoskeletal protein immunostaining in myelinated fibre tracts after focal cerebral ischaemia in the rat. Acta Neuropathol. 1997;93(1):71–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Dos Santos CD, Picanco-Diniz CW, Gomes-Leal W. Differential patterns of inflammatory response, axonal damage and myelin impairment following excitotoxic or ischemic damage to the trigeminal spinal nucleus of adult rats. Brain Res. 2007;1172:130–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Du Y, Dreyfus CF. Oligodendrocytes as providers of growth factors. J Neurosci Res. 2002;68(6):647–54.PubMedCrossRefGoogle Scholar
  34. 34.
    Dugas JC, Mandemakers W, Rogers M, Ibrahim A, Daneman R, Barres BA. A novel purification method for CNS projection neurons leads to the identification of brain vascular cells as a source of trophic support for corticospinal motor neurons. J Neurosci. 2008;28(33):8294–305.PubMedCrossRefGoogle Scholar
  35. 35.
    Esiri MM. The interplay between inflammation and neurodegeneration in CNS disease. J Neuroimmunol. 2007;184(1–2):4–16.PubMedCrossRefGoogle Scholar
  36. 36.
    Farkas E, Donka G, de Vos RA, Mihaly A, Bari F, Luiten PG. Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain. Acta Neuropathol. 2004;108(1):57–64.PubMedCrossRefGoogle Scholar
  37. 37.
    Farkas E, Luiten PG. Cerebral microvascular pathology in aging and Alzheimer’s disease. Prog Neurobiol. 2001;64(6):575–611.PubMedCrossRefGoogle Scholar
  38. 38.
    Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev. 2007;54(1):162–80.PubMedCrossRefGoogle Scholar
  39. 39.
    Flores AI, Mallon BS, Matsui T, Ogawa W, Rosenzweig A, Okamoto T, Macklin WB. Akt-mediated survival of oligodendrocytes induced by neuregulins. J Neurosci. 2000;20(20):7622–30.PubMedGoogle Scholar
  40. 40.
    Frost SB, Barbay S, Mumert ML, Stowe AM, Nudo RJ. An animal model of capsular infarct: endothelin-1 injections in the rat. Behav Brain Res. 2006;169(2):206–11.PubMedCrossRefGoogle Scholar
  41. 41.
    Gard AL, Burrell MR, Pfeiffer SE, Rudge JS, Williams II WC. Astroglial control of oligodendrocyte survival mediated by PDGF and leukemia inhibitory factor-like protein. Development. 1995;121(7):2187–97.PubMedGoogle Scholar
  42. 42.
    Gladstone DJ, Black SE, Hakim AM. Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions. Stroke. 2002;33(8):2123–36.PubMedCrossRefGoogle Scholar
  43. 43.
    Goldenberg-Cohen N, Guo Y, Margolis F, Cohen Y, Miller NR, Bernstein SL. Oligodendrocyte dysfunction after induction of experimental anterior optic nerve ischemia. Invest Ophthalmol Vis Sci. 2005;46(8):2716–25.PubMedCrossRefGoogle Scholar
  44. 44.
    Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H, et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007;6(12):1045–53.PubMedCrossRefGoogle Scholar
  45. 45.
    Greenberg DA, Jin K. From angiogenesis to neuropathology. Nature. 2005;438(7070):954–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Gregersen R, Christensen T, Lehrmann E, Diemer NH, Finsen B. Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain. Exp Brain Res. 2001;138(3):384–92.PubMedCrossRefGoogle Scholar
  47. 47.
    Griffiths I, Klugmann M, Anderson T, Thomson C, Vouyiouklis D, Nave KA. Current concepts of PLP and its role in the nervous system. Microsc Res Tech. 1998;41(5):344–58.PubMedCrossRefGoogle Scholar
  48. 48.
    Guo S, Kim WJ, Lok J, Lee SR, Besancon E, Luo BH, Stins MF, Wang X, Dedhar S, Lo EH. Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc Natl Acad Sci U S A. 2008;105(21):7582–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Guo S, Lo EH. Dysfunctional cell-cell signaling in the neurovascular unit as a paradigm for central nervous system disease. Stroke. 2009;40(3 Suppl):S4–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Hainsworth AH, Markus HS. Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab. 2008;28(12):1877–91.PubMedCrossRefGoogle Scholar
  51. 51.
    Hawkins BT, Davis TP. The blood–brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85.PubMedCrossRefGoogle Scholar
  52. 52.
    Hewitt KE, Stys PK, Lesiuk HJ. The use-dependent sodium channel blocker mexiletine is neuroprotective against global ischemic injury. Brain Res. 2001;898(2):281–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Hewlett KA, Corbett D. Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia. Neuroscience. 2006;141(1):27–33.PubMedCrossRefGoogle Scholar
  54. 54.
    Hughes PM, Anthony DC, Ruddin M, Botham MS, Rankine EL, Sablone M, Baumann D, Mir AK, Perry VH. Focal lesions in the rat central nervous system induced by endothelin-1. J Neuropathol Exp Neurol. 2003;62(12):1276–86.PubMedGoogle Scholar
  55. 55.
    Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004;5(5):347–60.PubMedCrossRefGoogle Scholar
  56. 56.
    Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci. 2007;10(11):1369–76.PubMedCrossRefGoogle Scholar
  57. 57.
    Ikonomidou C, Turski L. Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol. 2002;1(6):383–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Imai H, Masayasu H, Dewar D, Graham DI, Macrae IM. Ebselen protects both gray and white matter in a rodent model of focal cerebral ischemia. Stroke. 2001;32(9):2149–54.PubMedCrossRefGoogle Scholar
  59. 59.
    Imaizumi T, Kocsis JD, Waxman SG. Anoxic injury in the rat spinal cord: pharmacological evidence for multiple steps in Ca(2+)-dependent injury of the dorsal columns. J Neurotrauma. 1997;14(5):299–311.PubMedCrossRefGoogle Scholar
  60. 60.
    Irving EA, Bentley DL, Parsons AA. Assessment of white matter injury following prolonged focal cerebral ischaemia in the rat. Acta Neuropathol. 2001;102(6):627–35.PubMedGoogle Scholar
  61. 61.
    Irving EA, Yatsushiro K, McCulloch J, Dewar D. Rapid alteration of tau in oligodendrocytes after focal ischemic injury in the rat: involvement of free radicals. J Cereb Blood Flow Metab. 1997;17(6):612–22.PubMedCrossRefGoogle Scholar
  62. 62.
    James G, Butt AM. P2X and P2Y purinoreceptors mediate ATP-evoked calcium signalling in optic nerve glia in situ. Cell Calcium. 2001;30(4):251–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Johnson EC, Deppmeier LM, Wentzien SK, Hsu I, Morrison JC. Chronology of optic nerve head and retinal responses to elevated intraocular pressure. Invest Ophthalmol Vis Sci. 2000;41(2):431–42.PubMedGoogle Scholar
  64. 64.
    Karadottir R, Cavelier P, Bergersen LH, Attwell D. NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature. 2005;438(7071):1162–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Kawamura S, Yasui N, Shirasawa M, Fukasawa H. Rat middle cerebral artery occlusion using an intraluminal thread technique. Acta Neurochir (Wien). 1991;109(3–4):126–32.CrossRefGoogle Scholar
  66. 66.
    Kennedy TP, Vinten-Johansen J. A review of the clinical use of anti-inflammatory therapies for reperfusion injury in myocardial infarction and stroke: where do we go from here? Curr Opin Investig Drugs. 2006;7(3):229–42.PubMedGoogle Scholar
  67. 67.
    Knottnerus IL, Ten Cate H, Lodder J, Kessels F, van Oostenbrugge RJ. Endothelial dysfunction in lacunar stroke: a systematic review. Cerebrovasc Dis. 2009;27(5):519–26.PubMedCrossRefGoogle Scholar
  68. 68.
    Knox DL, Kerrison JB, Green WR. Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc. 2000;98:203–20; discussion 221–2.Google Scholar
  69. 69.
    Komitova M, Perfilieva E, Mattsson B, Eriksson PS, Johansson BB. Enriched environment after focal cortical ischemia enhances the generation of astroglia and NG2 positive polydendrocytes in adult rat neocortex. Exp Neurol. 2006;199(1):113–21.PubMedCrossRefGoogle Scholar
  70. 70.
    Krueger-Naug AM, Emsley JG, Myers TL, Currie RW, Clarke DB. Injury to retinal ganglion cells induces expression of the small heat shock protein Hsp27 in the rat visual system. Neuroscience. 2002;110(4):653–65.PubMedCrossRefGoogle Scholar
  71. 71.
    Le Feuvre RA, Brough D, Touzani O, Rothwell NJ. Role of P2X7 receptors in ischemic and excitotoxic brain injury in vivo. J Cereb Blood Flow Metab. 2003;23(3):381–4.PubMedCrossRefGoogle Scholar
  72. 72.
    Lee JM, Zipfel GJ, Choi DW. The changing landscape of ischaemic brain injury mechanisms. Nature. 1999;399(6738 Suppl):A7–14.PubMedCrossRefGoogle Scholar
  73. 73.
    Lee SR, Kim HY, Rogowska J, Zhao BQ, Bhide P, Parent JM, Lo EH. Involvement of matrix metalloproteinase in neuroblast cell migration from the subventricular zone after stroke. J Neurosci. 2006;26(13):3491–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Leventhal C, Rafii S, Rafii D, Shahar A, Goldman SA. Endothelial trophic support of neuronal production and recruitment from the adult mammalian subependyma. Mol Cell Neurosci. 1999;13(6):450–64.PubMedCrossRefGoogle Scholar
  75. 75.
    Levine JM, Reynolds R, Fawcett JW. The oligodendrocyte precursor cell in health and disease. Trends Neurosci. 2001;24(1):39–47.PubMedCrossRefGoogle Scholar
  76. 76.
    Lin S, Cox HJ, Rhodes PG, Cai Z. Neuroprotection of alpha-phenyl-n-tert-butyl-nitrone on the neonatal white matter is associated with anti-inflammation. Neurosci Lett. 2006;405(1–2):52–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Lin S, Rhodes PG, Lei M, Zhang F, Cai Z. Alpha-phenyl-n-tert-butyl-nitrone attenuates hypoxic-ischemic white matter injury in the neonatal rat brain. Brain Res. 2004;1007(1–2):132–41.PubMedCrossRefGoogle Scholar
  78. 78.
    Lipton SA. NMDA receptors, glial cells, and clinical medicine. Neuron. 2006;50(1):9–11.PubMedCrossRefGoogle Scholar
  79. 79.
    Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994;330(9):613–22.PubMedCrossRefGoogle Scholar
  80. 80.
    Lo EH. A new penumbra: transitioning from injury into repair after stroke. Nat Med. 2008;14(5):497–500.PubMedCrossRefGoogle Scholar
  81. 81.
    Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci. 2003;4(5):399–415.PubMedCrossRefGoogle Scholar
  82. 82.
    Lok J, Gupta P, Guo S, Kim WJ, Whalen MJ, van Leyen K, Lo EH. Cell-cell signaling in the neurovascular unit. Neurochem Res. 2007;32(12):2032–45.PubMedCrossRefGoogle Scholar
  83. 83.
    Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20:84–91.PubMedCrossRefGoogle Scholar
  84. 84.
    Lopes-Cardozo M, Sykes JE, Van der Pal RH, van Golde LM. Development of oligodendrocytes. Studies of rat glial cells cultured in chemically-defined medium. J Dev Physiol. 1989;12(3):117–27.PubMedGoogle Scholar
  85. 85.
    Louissaint Jr A, Rao S, Leventhal C, Goldman SA. Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron. 2002;34(6):945–60.PubMedCrossRefGoogle Scholar
  86. 86.
    Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA. Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther. 1973;14(5):852–61.PubMedGoogle Scholar
  87. 87.
    Mandai K, Matsumoto M, Kitagawa K, Matsushita K, Ohtsuki T, Mabuchi T, Colman DR, Kamada T, Yanagihara T. Ischemic damage and subsequent proliferation of oligodendrocytes in focal cerebral ischemia. Neuroscience. 1997;77(3):849–61.PubMedGoogle Scholar
  88. 88.
    Manning SM, Talos DM, Zhou C, Selip DB, Park HK, Park CJ, Volpe JJ, Jensen FE. NMDA receptor blockade with memantine attenuates white matter injury in a rat model of periventricular leukomalacia. J Neurosci. 2008;28(26):6670–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Masaki T, Yanagisawa M. Endothelins. Essays Biochem. 1992;27:79–89.PubMedGoogle Scholar
  90. 90.
    Matute C, Alberdi E, Domercq M, Sanchez-Gomez MV, Perez-Samartin A, Rodriguez-Antiguedad A, Perez-Cerda F. Excitotoxic damage to white matter. J Anat. 2007;210(6):693–702.PubMedCrossRefGoogle Scholar
  91. 91.
    McCarthy KD, de Vellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol. 1980;85(3):890–902.PubMedCrossRefGoogle Scholar
  92. 92.
    Medana IM, Esiri MM. Axonal damage: a key predictor of outcome in human CNS diseases. Brain. 2003;126(Pt 3):515–30.PubMedCrossRefGoogle Scholar
  93. 93.
    Merrill JE, Benveniste EN. Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci. 1996;19(8):331–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Micu I, Jiang Q, Coderre E, Ridsdale A, Zhang L, Woulfe J, Yin X, Trapp BD, McRory JE, Rehak R, et al. NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature. 2006;439(7079):988–92.PubMedGoogle Scholar
  95. 95.
    Miller RH. Oligodendrocyte origins. Trends Neurosci. 1996;19(3):92–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Motte S, McEntee K, Naeije R. Endothelin receptor antagonists. Pharmacol Ther. 2006;110(3):386–414.PubMedCrossRefGoogle Scholar
  97. 97.
    Nakaji K, Ihara M, Takahashi C, Itohara S, Noda M, Takahashi R, Tomimoto H. Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke. 2006;37(11):2816–23.PubMedCrossRefGoogle Scholar
  98. 98.
    Nave KA, Trapp BD. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci. 2008;31:535–61.PubMedCrossRefGoogle Scholar
  99. 99.
    Nishiyama A. NG2 cells in the brain: a novel glial cell population. Hum Cell. 2001;14(1):77–82.PubMedGoogle Scholar
  100. 100.
    Nishiyama A, Chang A, Trapp BD. NG2+ glial cells: a novel glial cell population in the adult brain. J Neuropathol Exp Neurol. 1999;58(11):1113–24.PubMedCrossRefGoogle Scholar
  101. 101.
    North RA. Molecular physiology of P2X receptors. Physiol Rev. 2002;82(4):1013–67.PubMedGoogle Scholar
  102. 102.
    Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ. Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms, and prevention. J Neurosci. 1993;13(4):1441–53.PubMedGoogle Scholar
  103. 103.
    Orthmann-Murphy JL, Abrams CK, Scherer SS. Gap junctions couple astrocytes and oligodendrocytes. J Mol Neurosci. 2008;35(1):101–16.PubMedCrossRefGoogle Scholar
  104. 104.
    Pang Y, Cai Z, Rhodes PG. Effects of lipopolysaccharide on oligodendrocyte progenitor cells are mediated by astrocytes and microglia. J Neurosci Res. 2000;62(4):510–20.PubMedCrossRefGoogle Scholar
  105. 105.
    Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis: a review. Stroke. 1997;28(3):652–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Pantoni L, Garcia JH, Gutierrez JA. Cerebral white matter is highly vulnerable to ischemia. Stroke. 1996;27(9):1641–6; discussion 1647.Google Scholar
  107. 107.
    Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol. 2002;52:802–13.PubMedCrossRefGoogle Scholar
  108. 108.
    Pfeiffer SE, Warrington AE, Bansal R. The oligodendrocyte and its many cellular processes. Trends Cell Biol. 1993;3(6):191–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Proctor PH, Tamborello LP. SAINT-I worked, but the neuroprotectant is not NXY-059. Stroke. 2007;38(10):e109; author reply e110.Google Scholar
  110. 110.
    Raber J, Fan Y, Matsumori Y, Liu Z, Weinstein PR, Fike JR, Liu J. Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Ann Neurol. 2004;55:381–9.PubMedCrossRefGoogle Scholar
  111. 111.
    Raff MC, Lillien LE, Richardson WD, Burne JF, Noble MD. Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature. 1988;333(6173):562–5.PubMedCrossRefGoogle Scholar
  112. 112.
    Raff MC, Miller RH, Noble M. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature. 1983;303(5916):390–6.PubMedCrossRefGoogle Scholar
  113. 113.
    Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev. 1998;50(3):413–92.PubMedGoogle Scholar
  114. 114.
    Rosenberg GA, Sullivan N, Esiri MM. White matter damage is associated with matrix metalloproteinases in vascular dementia. Stroke. 2001;32(5):1162–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Rosenberg SS, Ng BK, Chan JR. The quest for remyelination: a new role for neurotrophins and their receptors. Brain Pathol. 2006;16(4):288–94.PubMedCrossRefGoogle Scholar
  116. 116.
    Rubanyi GM, Polokoff MA. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev. 1994;46(3):325–415.PubMedGoogle Scholar
  117. 117.
    Rubio N, Rodriguez R, Arevalo MA. In vitro myelination by oligodendrocyte precursor cells transfected with the neurotrophin-3 gene. Glia. 2004;47(1):78–87.PubMedCrossRefGoogle Scholar
  118. 118.
    Saivin S, Houin G. Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet. 1988;15(6):355–66.PubMedCrossRefGoogle Scholar
  119. 119.
    Salter MG, Fern R. NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature. 2005;438(7071):1167–71.PubMedCrossRefGoogle Scholar
  120. 120.
    Sanchez-Gomez MV, Alberdi E, Ibarretxe G, Torre I, Matute C. Caspase-dependent and caspase-independent oligodendrocyte death mediated by AMPA and kainate receptors. J Neurosci. 2003;23(29):9519–28.PubMedGoogle Scholar
  121. 121.
    Sarti C, Pantoni L, Bartolini L, Inzitari D. Cognitive impairment and chronic cerebral hypoperfusion: what can be learned from experimental models. J Neurol Sci. 2002;203–204:263–6.PubMedCrossRefGoogle Scholar
  122. 122.
    Schabitz WR, Li F, Fisher M. The N-methyl-D-aspartate antagonist CNS 1102 protects cerebral gray and white matter from ischemic injury following temporary focal ischemia in rats. Stroke. 2000;31(7):1709–14.PubMedCrossRefGoogle Scholar
  123. 123.
    Schmidt R, Scheltens P, Erkinjuntti T, Pantoni L, Markus HS, Wallin A, Barkhof F, Fazekas F. White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease. Neurology. 2004;63(1):139–44.PubMedCrossRefGoogle Scholar
  124. 124.
    Selles-Navarro I, Ellezam B, Fajardo R, Latour M, McKerracher L. Retinal ganglion cell and nonneuronal cell responses to a microcrush lesion of adult rat optic nerve. Exp Neurol. 2001;167(2):282–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N, Vincent P, Pumiglia K, Temple S. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004;304(5675):1338–40.PubMedCrossRefGoogle Scholar
  126. 126.
    Shibata M, Ohtani R, Ihara M, Tomimoto H. White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke. 2004;35(11):2598–603.PubMedCrossRefGoogle Scholar
  127. 127.
    Shibata M, Yamasaki N, Miyakawa T, Kalaria RN, Fujita Y, Ohtani R, Ihara M, Takahashi R, Tomimoto H. Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke. 2007;38(10):2826–32.PubMedCrossRefGoogle Scholar
  128. 128.
    Souza-Rodrigues RD, Costa AM, Lima RR, Dos Santos CD, Picanco-Diniz CW, Gomes-Leal W. Inflammatory response and white matter damage after microinjections of endothelin-1 into the rat striatum. Brain Res. 2008;1200:78–88.PubMedCrossRefGoogle Scholar
  129. 129.
    Sozmen EG, Kolekar A, Havton LA, Carmichael ST. A white matter stroke model in the mouse: axonal damage, progenitor responses and MRI correlates. J Neurosci Methods. 2009;180(2):261–72.PubMedCrossRefGoogle Scholar
  130. 130.
    Stolp HB, Ek CJ, Johansson PA, Dziegielewska KM, Potter AM, Habgood MD, Saunders NR. Effect of minocycline on inflammation-induced damage to the blood–brain barrier and white matter during development. Eur J Neurosci. 2007;26(12):3465–74.PubMedCrossRefGoogle Scholar
  131. 131.
    Stys PK. White matter injury mechanisms. Curr Mol Med. 2004;4(2):113–30.PubMedCrossRefGoogle Scholar
  132. 132.
    Stys PK, Jiang Q. Calpain-dependent neurofilament breakdown in anoxic and ischemic rat central axons. Neurosci Lett. 2002;328(2):150–4.PubMedCrossRefGoogle Scholar
  133. 133.
    Stys PK, Ransom BR, Waxman SG. Tertiary and quaternary local anesthetics protect CNS white matter from anoxic injury at concentrations that do not block excitability. J Neurophysiol. 1992;67(1):236–40.PubMedGoogle Scholar
  134. 134.
    Takahashi JL, Giuliani F, Power C, Imai Y, Yong VW. Interleukin-1beta promotes oligodendrocyte death through glutamate excitotoxicity. Ann Neurol. 2003;53(5):588–95.PubMedCrossRefGoogle Scholar
  135. 135.
    Tamura A, Graham DI, McCulloch J, Teasdale GM. Focal cerebral ischemia in the rat: description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1981;1:53–60.PubMedCrossRefGoogle Scholar
  136. 136.
    Tanaka K, Nogawa S, Suzuki S, Dembo T, Kosakai A. Upregulation of oligodendrocyte progenitor cells associated with restoration of mature oligodendrocytes and myelination in peri-infarct area in the rat brain. Brain Res. 2003;989(2):172–9.PubMedCrossRefGoogle Scholar
  137. 137.
    Ueno Y, Zhang N, Miyamoto N. Edaravone attenuates white matter lesions through endothelial protection in a rat chronic hypoperfusion model. Neuroscience. 2009;162(2):317–27.PubMedCrossRefGoogle Scholar
  138. 138.
    Valeriani V, Dewar D, McCulloch J. Quantitative assessment of ischemic pathology in axons, oligodendrocytes, and neurons: attenuation of damage after transient ischemia. J Cereb Blood Flow Metab. 2000;20(5):765–71.PubMedCrossRefGoogle Scholar
  139. 139.
    Volpe JJ. Cerebral white matter injury of the premature infant-more common than you think. Pediatrics. 2003;112(1 Pt 1):176–80.PubMedCrossRefGoogle Scholar
  140. 140.
    Wahlgren NG, Ahmed N. Neuroprotection in cerebral ischaemia: facts and fancies—the need for new approaches. Cerebrovasc Dis. 2004;17 Suppl 1:153–66.PubMedCrossRefGoogle Scholar
  141. 141.
    Wakita H, Tomimoto H, Akiguchi I, Matsuo A, Lin JX, Ihara M, McGeer PL. Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat. Brain Res. 2002;924(1):63–70.PubMedCrossRefGoogle Scholar
  142. 142.
    Wang CX, Shuaib A. Neuroprotective effects of free radical scavengers in stroke. Drugs Aging. 2007;24(7):537–46.PubMedCrossRefGoogle Scholar
  143. 143.
    Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA, et al. P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med. 2004;10(8):821–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Yonezawa M, Back SA, Gan X, Rosenberg PA, Volpe JJ. Cystine deprivation induces oligodendroglial death: rescue by free radical scavengers and by a diffusible glial factor. J Neurochem. 1996;67(2):566–73.PubMedCrossRefGoogle Scholar
  145. 145.
    Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci U S A. 1998;95(26):15769–74.PubMedCrossRefGoogle Scholar
  146. 146.
    Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A. 1999;96(23):13496–500.PubMedCrossRefGoogle Scholar
  147. 147.
    Zacchigna S, Lambrechts D, Carmeliet P. Neurovascular signalling defects in neurodegeneration. Nat Rev Neurosci. 2008;9(3):169–81.PubMedCrossRefGoogle Scholar
  148. 148.
    Zhang J, Li Y, Zheng X, Gao Q, Liu Z, Qu R, Borneman J, Elias SB, Chopp M. Bone marrow stromal cells protect oligodendrocytes from oxygen-glucose deprivation injury. J Neurosci Res. 2008;86(7):1501–10.PubMedCrossRefGoogle Scholar
  149. 149.
    Zhang K, Sejnowski TJ. A universal scaling law between gray matter and white matter of cerebral cortex. Proc Natl Acad Sci U S A. 2000;97(10):5621–6.PubMedCrossRefGoogle Scholar
  150. 150.
    Zhang Z, Chopp M, Zhang RL, Goussev A. A mouse model of embolic focal cerebral ischemia. J Cereb Blood Flow Metab. 1997;17:1081–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Zhang ZG, Zhang RL, Jiang Q, Raman SB, Cantwell L, Chopp M. A new rat model of thrombotic focal cerebral ischemia. J Cereb Blood Flow Metab. 1997;17:123–35.PubMedCrossRefGoogle Scholar
  152. 152.
    Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, Wang X, Lo EH. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med. 2006;12(4):441–5.PubMedCrossRefGoogle Scholar
  153. 153.
    Zhu X, Bergles DE, Nishiyama A. NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development. 2008;135(1):145–57.PubMedCrossRefGoogle Scholar
  154. 154.
    Zlokovic BV. The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57(2):178–201.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Neuroprotection Research LaboratoryMassachusetts General Hospital/Harvard Medical SchoolCharlestownUSA

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