Advertisement

Oxidative Stress in White Matter Injury

  • Hideyuki Yoshioka
  • Takuma Wakai
  • Hiroyuki Kinouchi
  • Pak H. Chan
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR, volume 4)

Abstract

White matter is the region of the brain underlying gray matter and comprises over half the human brain. Its elements, axons, oligodendrocytes (myelin-producing cells), and oligodendroglia progenitor cells, are exceedingly vulnerable to oxidative stress, since axons contain abundant mitochondria (organelles that are a main source of reactive oxygen species), and the myelin sheath contains numerous lipids, which can be peroxidized after oxidative stress. In addition, low levels of reduced glutathione and high levels of iron content in oligodendrocytes and oligodendrocyte progenitors contribute to this vulnerability. White matter is at risk for oxidative ischemic injury throughout life, from periventricular white matter injury in neonates to stroke and vascular dementia in later life. Prevention of oxidative stress could be a clinical strategy for ischemic white matter injury.

Keywords

White Matter Corpus Callosum Middle Cerebral Artery Occlusion White Matter Lesion White Matter Injury 
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.

Abbreviations

4-HNE

4-Hydroxynonenal

APP

Amyloid precursor protein

eNOS

Endothelium nitric oxide synthase

H2O2

Hydrogen peroxide

iNOS

Inducible nitric oxide synthase

MBP

Myelin basic protein

MCA

Middle cerebral artery

MDA

Malondialdehyde

nNOS

Neuronal nitric oxide synthase

NO

Nitric oxide

NOS

Nitric oxide synthase

NOX

Nicotinamide adenine dinucleotide phosphate oxidase

O2•−

Superoxide anions

OH

Hydroxyl radicals

ONOO

Peroxynitrite

PWMI

Periventricular white matter injury

RIP

Receptor-interacting protein

ROS

Reactive oxygen species

SMI-32

An antibody against a non-phosphorylated neurofilament epitope

SOD

Superoxide dismutase

SOD1

Copper/zinc superoxide dismutase

SOD2

Manganese superoxide dismutase

Notes

Acknowledgments

  We thank Liza Reola and Bernard Calagui for technical assistance.

This work was supported by grants PO1 NS014543, RO1 NS025372, and RO1 NS038653, from the National Institutes of Health, and by the James R. Doty Endowment.

References

  1. Arvin KL, Han BH, Du Y, S-Z L, Paul SM, Holtzman DM (2002) Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. Ann Neurol 52:54–61CrossRefPubMedGoogle Scholar
  2. Back SA, Rivkees SA (2004) Emerging concepts in periventricular white matter injury. Semin Perinatol 28:405–414CrossRefPubMedGoogle Scholar
  3. Back SA, Volpe JJ (1997) Cellular and molecular pathogenesis of periventricular white matter injury. Ment Retard Dev Disabil Res Rev 3:96–107CrossRefGoogle Scholar
  4. Back SA, Han BH, Luo NL, Chricton CA, Xanthoudakis S, Tam J, Arvin KL, Holtzman DM (2002) Selective vulnerability of late oligodendrocyte progenitors to hypoxia–ischemia. J Neurosci 22:455–463PubMedGoogle Scholar
  5. Baud O, Haynes RF, Wang H, Folkerth RD, Li J, Volpe JJ, Rosenberg PA (2004) Developmental up-regulation of MnSOD in rat oligodendrocytes confers protection against oxidative injury. Eur J Neurosci 20:29–40CrossRefPubMedGoogle Scholar
  6. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87:1620–1624CrossRefPubMedGoogle Scholar
  7. Bedard K, Krause K-H (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313CrossRefPubMedGoogle Scholar
  8. Bernardo A, Greco A, Levi G, Minghetti L (2003) Differential lipid peroxidation, Mn superoxide, and bcl-2 expression contribute to the maturation-dependent vulnerability of oligodendrocytes to oxidative stress. J Neuropathol Exp Neurol 62:509–519PubMedGoogle Scholar
  9. Bogousslavsky J, Regli F (1992) Centrum ovale infarcts: subcortical infarction in the superficial territory of the middle cerebral artery. Neurology 42:1992–1998CrossRefPubMedGoogle Scholar
  10. Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. general properties and effect of hyperbaric oxygen. Biochem J 134:707–716PubMedGoogle Scholar
  11. Cai Z, Lin S, Fan L-W, Pang Y, Rhodes PG (2006) Minocycline alleviates hypoxic–ischemic injury to developing oligodendrocytes in the neonatal rat brain. Neuroscience 137:425–435CrossRefPubMedGoogle Scholar
  12. Chan PH (1996) Role of oxidants in ischemic brain damage. Stroke 27:1124–1129CrossRefPubMedGoogle Scholar
  13. Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14CrossRefPubMedGoogle Scholar
  14. Cheepsunthorn P, Palmer C, Connor JR (1998) Cellular distribution of ferritin subunits in postnatal rat brain. J Comp Neurol 400:73–86CrossRefPubMedGoogle Scholar
  15. Cheepsunthorn P, Palmer C, Menzies S, Roberts RL, Connor JR (2001) Hypoxic/ischemic insult alters ferritin expression and myelination in neonatal rat brains. J Comp Neurol 431:382–396CrossRefPubMedGoogle Scholar
  16. Chen H, Song YS, Chan PH (2009) Inhibition of NADPH oxidase is neuroprotective after ischemia–reperfusion. J Cereb Blood Flow Metab 29:1262–1272CrossRefPubMedGoogle Scholar
  17. Chen H, Yoshioka H, Kim GS, Jung JE, Okami N, Sakata H, Maier CM, Narasimhan P, Goeders CE, Chan PH (2011) Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid Redox Signal 14:1505–1517CrossRefPubMedGoogle Scholar
  18. Connor JR, Menzies SL (1996) Relationship of iron to oligodendrocytes and myelination. Glia 17:83–93CrossRefPubMedGoogle Scholar
  19. Craig A, Luo NL, Beardsley DJ, Wingate-Pearse N, Walker DW, Hohimer AR, Back SA (2003) Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human. Exp Neurol 181:231–240CrossRefPubMedGoogle Scholar
  20. Deguchi K, Mizuguchi M, Takashima S (1996) Immunohistochemical expression of tumor necrosis factor α in neonatal leukomalacia. Pediatr Neurol 14:13–16CrossRefPubMedGoogle Scholar
  21. Dewar D, Dawson D (1995) Tau protein is altered by focal cerebral ischaemia in the rat: an immunohistochemical and immunoblotting study. Brain Res 684:70–78CrossRefPubMedGoogle Scholar
  22. Dewar D, Yam P, McCulloch J (1999) Drug development for stroke: importance of protecting cerebral white matter. Eur J Pharmacol 375:41–50CrossRefPubMedGoogle Scholar
  23. Dewar D, Underhill SM, Goldberg MP (2003) Oligodendrocytes and ischemic brain injury. J Cereb Blood Flow Metab 23:263–274CrossRefPubMedGoogle Scholar
  24. Dietrich WD, Kraydieh S, Prado R, Stagliano NE (1998) White matter alterations following thromboembolic stroke: a β-amyloid precursor protein immunocytochemical study in rats. Acta Neuropathol 95:524–531CrossRefPubMedGoogle Scholar
  25. Dong Y-F, Kataoka K, Toyama K, Sueta D, Koibuchi N, Yamamoto E, Yata K, Tomimoto H, Ogawa H, Kim-Mitsuyama S (2011) Attenuation of brain damage and cognitive impairment by direct renin inhibition in mice with chronic cerebral hypoperfusion. Hypertension 58: 635–642CrossRefPubMedGoogle Scholar
  26. Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95PubMedGoogle Scholar
  27. Farkas E, Donka G, de Vos RAI, Mihály A, Bari F, Luiten PGM (2004) Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain. Acta Neuropathol 108:57–64CrossRefPubMedGoogle Scholar
  28. Fern R, Möller T (2000) Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci 20:34–42PubMedGoogle Scholar
  29. Fields RD (2008) White matter in learning, cognition and psychiatric disorders. Trends Neurosci 31:361–370CrossRefPubMedGoogle Scholar
  30. Folkerth RD, Haynes RL, Borenstein NS, Belliveau RA, Trachtenberg F, Rosenberg PA, Volpe JJ, Kinney HC (2004a) Developmental lag in superoxide dismutases relative to other antioxidant enzymes in premyelinated human telencephalic white matter. J Neuropathol Exp Neurol 63:990–999PubMedGoogle Scholar
  31. Folkerth RD, Keefe RJ, Haynes RL, Trachtenberg FL, Volpe JJ, Kinney HC (2004b) Interferon-γ expression in periventricular leukomalacia in the human brain. Brain Pathol 14:265–274CrossRefPubMedGoogle Scholar
  32. Gerstner B, Lee J, DeSilva TM, Jensen FE, Volpe JJ, Rosenberg PA (2009) 17β-Estradiol protects against hypoxic/ischemic white matter damage in the neonatal rat brain. J Neurosci Res 87: 2078–2086CrossRefPubMedGoogle Scholar
  33. Ginsberg MD, Busto R (1989) Rodent models of cerebral ischemia. Stroke 20:1627–1642CrossRefPubMedGoogle Scholar
  34. Gresle MM, Jarrott B, Jones NM, Callaway JK (2006) Injury to axons and oligodendrocytes following endothelin-1-induced middle cerebral artery occlusion in conscious rats. Brain Res 1110:13–22CrossRefPubMedGoogle Scholar
  35. Halliwell B (1989) Oxidants and the central nervous system: some fundamental questions. Is oxidant damage relevant to Parkinson’s disease, Alzheimer’s disease, traumatic injury or stroke? Acta Neurol Scand Suppl 126:23–33CrossRefPubMedGoogle Scholar
  36. Harrison PM, Arosio P (1996) The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1275:161–203CrossRefPubMedGoogle Scholar
  37. Hattori H, Takeda M, Kudo T, Nishimura T, Hashimoto S (1992) Cumulative white matter changes in the gerbil brain under chronic cerebral hypoperfusion. Acta Neuropathol 84:437–442CrossRefPubMedGoogle Scholar
  38. Haynes RL, Folkerth RD, Keefe RJ, Sung I, Swzeda LI, Rosenberg PA, Volpe JJ, Kinney HC (2003) Nitrosative and oxidative injury to premyelinating oligodendrocytes in periventricular leukomalacia. J Neuropathol Exp Neurol 62:441–450PubMedGoogle Scholar
  39. Haynes RL, Baud O, Li J, Kinney HC, Volpe JJ, Folkerth RD (2005) Oxidative and nitrative injury in periventricular leukomalacia: a review. Brain Pathol 15:225–233CrossRefPubMedGoogle Scholar
  40. Husain J, Juurlink BHJ (1995) Oligodendroglial precursor cell susceptibility to hypoxia is related to poor ability to cope with reactive oxygen species. Brain Res 698:86–94CrossRefPubMedGoogle Scholar
  41. Ihara M, Tomimoto H, Kinoshita M, Oh J, Noda M, Wakita H, Akiguchi I, Shibasaki H (2001) Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter. J Cereb Blood Flow Metab 21:828–834CrossRefPubMedGoogle Scholar
  42. Imai H, Masayasu H, Dewar D, Graham DI, Macrae IM (2001) Ebselen protects both gray and white matter in a rodent model of focal cerebral ischemia. Stroke 32:2149–2154CrossRefPubMedGoogle Scholar
  43. Infanger DW, Sharma RV, Davisson RL (2006) NADPH oxidases of the brain: distribution, regulation, and function. Antioxid Redox Signal 8:1583–1596CrossRefPubMedGoogle Scholar
  44. Irving EA, Yatsushiro K, McCulloch J, Dewar D (1997) Rapid alteration of tau in oligodendrocytes after focal ischemic injury in the rat: involvement of free radicals. J Cereb Blood Flow Metab 17:612–622CrossRefPubMedGoogle Scholar
  45. Irving EA, Bentley DL, Parsons AA (2001) Assessment of white matter injury following prolonged focal cerebral ischaemia in the rat. Acta Neuropathol 102:627–635PubMedGoogle Scholar
  46. Iwai M, Liu H-W, Chen R, Ide A, Okamoto S, Hata R, Sakanaka M, Shiuchi T, Horiuchi M (2004) Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation. Circulation 110:843–848CrossRefPubMedGoogle Scholar
  47. Juurlink BHJ, Thorburne SK, Hertz L (1998) Peroxide-scavenging deficit underlies oligodendrocyte susceptibility to oxidative stress. Glia 22:371–378CrossRefPubMedGoogle Scholar
  48. Kadhim H, Tabarki B, Verellen G, De Prez C, Rona A-M, Sébire G (2001) Inflammatory cytokines in the pathogenesis of periventricular leukomalacia. Neurology 56:1278–1284CrossRefPubMedGoogle Scholar
  49. Kadhim H, Tabarki B, De Prez C, Rona A-M, Sébire G (2002) Interleukin-2 in the pathogenesis of perinatal white matter damage. Neurology 58:1125–1128CrossRefPubMedGoogle Scholar
  50. Kim YS, Kim SU (1991) Oligodendroglial cell death induced by oxygen radicals and its protection by catalase. J Neurosci Res 29:100–106CrossRefPubMedGoogle Scholar
  51. Kim MJ, Shin K-S, Chung Y-B, Jung KW, Cha CI, Shin DH (2005) Immunohistochemical study of p47Phox and gp91Phox distributions in rat brain. Brain Res 1040:178–186CrossRefPubMedGoogle Scholar
  52. Kim J-S, Yun I, Choi YB, Lee K-S, Kim Y-I (2008) Ramipril protects from free radical induced white matter damage in chronic hypoperfusion in the rat. J Clin Neurosci 15:174–178CrossRefPubMedGoogle Scholar
  53. Kim GS, Jung JE, Niizuma K, Chan PH (2009) CK2 is a novel negative regulator of NADPH oxidase and a neuroprotectant in mice after cerebral ischemia. J Neurosci 29:14779–14789CrossRefPubMedGoogle Scholar
  54. Kinouchi H, Epstein CJ, Mizui T, Carlson E, Chen SF, Chan PH (1991) Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc Natl Acad Sci U S A 88:11158–11162CrossRefPubMedGoogle Scholar
  55. Kubo K, Nakao S, Jomura S, Sakamoto S, Miyamoto E, Xu Y, Tomimoto H, Inada T, Shingu K (2009) Edaravone, a free radical scavenger, mitigates both gray and white matter damages after global cerebral ischemia in rats. Brain Res 1279:139–146CrossRefPubMedGoogle Scholar
  56. Kudo T, Takeda M, Tanimukai S, Nishimura T (1993) Neuropathologic changes in the gerbil brain after chronic hypoperfusion. Stroke 24:259–264CrossRefPubMedGoogle Scholar
  57. Kurumatani T, Kudo T, Ikura Y, Takeda M (1998) White matter changes in the gerbil brain under chronic cerebral hypoperfusion. Stroke 29:1058–1062CrossRefPubMedGoogle Scholar
  58. Li J, Baud O, Vartanian T, Volpe JJ, Rosenberg PA (2005) Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes. Proc Natl Acad Sci U S A 102:9936–9941CrossRefPubMedGoogle Scholar
  59. Lin S, Rhodes PG, Lei M, Zhang F, Cai Z (2004) α-Phenyl-n-tert-butyl-nitrone attenuates hypoxic–ischemic white matter injury in the neonatal rat brain. Brain Res 1007:132–141CrossRefPubMedGoogle Scholar
  60. Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–415CrossRefPubMedGoogle Scholar
  61. Lyons SA, Kettenmann H (1998) Oligodendrocytes and microglia are selectively vulnerable to combined hypoxia and hypoglycemia injury in vitro. J Cereb Blood Flow Metab 18:521–530CrossRefPubMedGoogle Scholar
  62. McTigue DM, Tripathi RB (2008) The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem 107:1–19CrossRefPubMedGoogle Scholar
  63. Mitrovic B, Ignarro LJ, Vinters HV, Akers M-A, Schmid I, Uittenbogaart C, Merrill JE (1995) Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes. Neuroscience 65:531–539CrossRefPubMedGoogle Scholar
  64. Mitrovic B, Parkinson J, Merrill JE (1996) An in vitro model of oligodendrocyte destruction by nitric oxide and its relevance to multiple sclerosis. Methods 10:501–513CrossRefPubMedGoogle Scholar
  65. Moxon-Emre I, Schlichter LC (2010) Evolution of inflammation and white matter injury in a model of transient focal ischemia. J Neuropathol Exp Neurol 69:1–15CrossRefPubMedGoogle Scholar
  66. Niizuma K, Yoshioka H, Chen H, Kim GS, Jung JE, Katsu M, Okami N, Chan PH (2010) Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia. Biochim Biophys Acta 1802:92–99CrossRefPubMedGoogle Scholar
  67. Noble PG, Antel JP, Yong VW (1994) Astrocytes and catalase prevent the toxicity of catecholamines to oligodendrocytes. Brain Res 633:83–90CrossRefPubMedGoogle Scholar
  68. Pantoni L, Garcia JH (1997) Pathogenesis of leukoaraiosis. Stroke 28:652–659CrossRefPubMedGoogle Scholar
  69. Pantoni L, Garcia JH, Gutierrez JA (1996) Cerebral white matter is highly vulnerable to ischemia. Stroke 27:1641–1646CrossRefPubMedGoogle Scholar
  70. Petito CK, Olarte J-P, Roberts B, Nowak TS Jr, Pulsinelli WA (1998) Selective glial vulnerability following transient global ischemia in rat brain. J Neuropathol Exp Neurol 57:231–238CrossRefPubMedGoogle Scholar
  71. Pluta R, Ułamek M, Januszewski S (2006) Micro-blood-brain barrier openings and cytotoxic fragments of amyloid precursor protein accumulation in white matter after ischemic brain injury in long-lived rats. Acta Neurochir Suppl 96:267–271CrossRefPubMedGoogle Scholar
  72. Ravati A, Junker V, Kouklei M, Ahlemeyer B, Culmsee C, Krieglstein J (1999) Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats. Eur J Pharmacol 373:21–33CrossRefPubMedGoogle Scholar
  73. Shen Y, Liu X-B, Pleasure DE, Deng W (2012) Axon–glia synapses are highly vulnerable to white matter injury in the developing brain. J Neurosci Res 90:105–121CrossRefPubMedGoogle Scholar
  74. Shibata M, Ohtani R, Ihara M, Tomimoto H (2004) White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35:2598–2603CrossRefPubMedGoogle Scholar
  75. Shigematsu K, McGeer PL (1992) Accumulation of amyloid precursor protein in neurons after intraventricular injection of colchicine. Am J Pathol 140:787–794PubMedGoogle Scholar
  76. Souza-Rodrigues RD, Costa AMR, Lima RR, Dos Santos CD, Picanço-Diniz CW, Gomes-Leal W (2008) Inflammatory response and white matter damage after microinjections of endothelin-1 into the rat striatum. Brain Res 1200:78–88CrossRefPubMedGoogle Scholar
  77. Sozmen EG, Kolekar A, Havton LA, Carmichael ST (2009) A white matter stroke model in the mouse: axonal damage, progenitor responses and MRI correlates. J Neurosci Methods 180: 261–272CrossRefPubMedGoogle Scholar
  78. Stephenson DT, Rash K, Clemens JA (1992) Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat. Brain Res 593:128–135CrossRefPubMedGoogle Scholar
  79. Sugawara T, Kinouchi H, Oda M, Shoji H, Omae T, Mizoi K (2005) Candesartan reduces superoxide production after global cerebral ischemia. Neuroreport 16:325–328CrossRefPubMedGoogle Scholar
  80. Takizawa S, Fukuyama N, Hirabayashi H, Kohara S, Kazahari S, Shinohara Y, Nakazawa H (2003) Quercetin, a natural flavonoid, attenuates vacuolar formation in the optic tract in rat chronic cerebral hypoperfusion model. Brain Res 980:156–160CrossRefPubMedGoogle Scholar
  81. Tejada-Simon MV, Serrano F, Villasana LE, Kanterewicz BI, Wu G-Y, Quinn MT, Klann E (2005) Synaptic localization of a functional NADPH oxidase in the mouse hippocampus. Mol Cell Neurosci 29:97–106CrossRefPubMedGoogle Scholar
  82. Thorburne SK, Juurlink BHJ (1996) Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress. J Neurochem 67:1014–1022CrossRefPubMedGoogle Scholar
  83. Trapp BD, Stys PK (2009) Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol 8:280–291CrossRefPubMedGoogle Scholar
  84. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285CrossRefPubMedGoogle Scholar
  85. Ueno M, Tomimoto H, Akiguchi I, Wakita H, Sakamoto H (2002) Blood–brain barrier disruption in white matter lesions in a rat model of chronic cerebral hypoperfusion. J Cereb Blood Flow Metab 22:97–104CrossRefPubMedGoogle Scholar
  86. Ueno Y, Zhang N, Miyamoto N, Tanaka R, Hattori N, Urabe T (2009) Edaravone attenuates white matter lesions through endothelial protection in a rat chronic hypoperfusion model. Neuroscience 162:317–327CrossRefPubMedGoogle Scholar
  87. Wakai T, Yoshioka H, Yagi T, Kato T, Kinouchi H (2011) Effects of valsartan on neuroprotection and neurogenesis after ischemia. Neuroreport 22:385–390CrossRefPubMedGoogle Scholar
  88. Wakita H, Tomimoto H, Akiguchi I, Kimura J (1994) Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunohistochemical study. Acta Neuropathol 87:484–492CrossRefPubMedGoogle Scholar
  89. Walder CE, Green SP, Darbonne WC, Mathias J, Rae J, Dinauer MC, Curnutte JT, Thomas GR (1997) Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase. Stroke 28:2252–2258CrossRefPubMedGoogle Scholar
  90. Walker EJ, Rosenberg GA (2010) Divergent role for MMP-2 in myelin breakdown and oligodendrocyte death following transient global ischemia. J Neurosci Res 88:764–773PubMedGoogle Scholar
  91. Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R (2010) Nonhypotensive dose of telmisartan attenuates cognitive impairment partially due to peroxisome proliferator-activated receptor-γ activation in mice with chronic cerebral hypoperfusion. Stroke 41:1798–1806CrossRefPubMedGoogle Scholar
  92. Watanabe T, Zhang N, Liu M, Tanaka R, Mizuno Y, Urabe T (2006) Cilostazol protects against brain white matter damage and cognitive impairment in a rat model of chronic cerebral hypoperfusion. Stroke 37:1539–1545CrossRefPubMedGoogle Scholar
  93. Xing C, Arai K, Lo EH, Hommel M (2012) Pathophysiologic cascades in ischemic stroke. Int J Stroke 7:378–385CrossRefPubMedGoogle Scholar
  94. Xu J, He L, Ahmed SH, Chen S-W, Goldberg MP, Beckman JS, Hsu CY (2000) Oxygen-glucose deprivation induces inducible nitric oxide synthase and nitrotyrosine expression in cerebral endothelial cells. Stroke 31:1744–1751CrossRefPubMedGoogle Scholar
  95. Xu L, Fagan SC, Waller JL, Edwards D, Borlongan CV, Zheng J, Hill WD, Feuerstein G, Hess DC (2004) Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol 4:7CrossRefPubMedGoogle Scholar
  96. Yam PS, Takasago T, Dewar D, Graham DI, McCulloch J (1997) Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion. Brain Res 760:150–157CrossRefPubMedGoogle Scholar
  97. Yoon BH, Romero R, Kim CJ, Koo JN, Choe G, Syn HC, Chi JG (1997) High expression of tumor necrosis factor-α and interleukin-6 in periventricular leukomalacia. Am J Obstet Gynecol 177:406–411CrossRefPubMedGoogle Scholar
  98. Yoshioka H, Niizuma K, Katsu M, Okami N, Sakata H, Kim GS, Narasimhan P, Chan PH (2011a) NADPH oxidase mediates striatal neuronal injury after transient global cerebral ischemia. J Cereb Blood Flow Metab 31:868–880CrossRefPubMedGoogle Scholar
  99. Yoshioka H, Niizuma K, Katsu M, Sakata H, Okami N, Chan PH (2011b) Consistent injury to medium spiny neurons and white matter in the mouse striatum after prolonged transient global cerebral ischemia. J Neurotrauma 28:649–660CrossRefPubMedGoogle Scholar
  100. Yrjänheikki J, Keinänen R, Pellikka M, Hökfelt T, Koistinaho J (1998) Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci U S A 95:15769–15774CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Hideyuki Yoshioka
    • 1
    • 2
    • 3
    • 4
  • Takuma Wakai
    • 1
    • 2
    • 3
    • 4
  • Hiroyuki Kinouchi
    • 4
  • Pak H. Chan
    • 1
    • 2
    • 3
  1. 1.Department of NeurosurgeryStanford University School of MedicineStanfordUSA
  2. 2.Department of Neurology and Neurological SciencesStanford University School of MedicineStanfordUSA
  3. 3.Program in NeurosciencesStanford University School of MedicineStanfordUSA
  4. 4.Department of Neurosurgery, Interdisciplinary Graduate School of Medicine and EngineeringUniversity of YamanashiYamanashiJapan

Personalised recommendations