Skip to main content
SpringerLink
Log in

Age-Dependent Mechanisms of White Matter Injury After Stroke

  • Chapter
  • First Online:
White Matter Injury in Stroke and CNS Disease

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR,volume 4))

Abstract

White matter is affected in human stroke and treatment strategies derived from experimental work on young adults focused exclusively on gray matter have been ineffective in the more clinically relevant aging population. The risk for stroke increases with age and the white matter also inherently becomes more vulnerable to injury with age. Age-related changes in the molecular architecture of white matter dictate the predominant injury mechanisms and determine the functional outcome. A prominent increase in the main Na+-dependent glutamate transporter, GLT-1, together with increased glutamate levels may reflect an increased need for glutamate signaling in the aging white matter to maintain function. Conversely, these adaptive modifications become detrimental under ischemic conditions, leading to increased vulnerability and robust injury. Mitochondria gather and elongate to effectively buffer Ca2+ but fail to produce sufficient ATP during an ischemic challenge to sustain aging axon function. Consequently, protective interventions in young white matter become injurious or ineffective to promote recovery in aging white matter after an ischemic episode. An age-specific understanding of the mechanisms of injury processes in white matter is essential to design dynamic therapeutic approaches for stroke victims.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agrawal SK, Fehlings MG (1997) Role of NMDA and non-NMDA ionotropic glutamate receptors in traumatic spinal cord axonal injury. J Neurosci 17:1055–1063

    PubMed  CAS  Google Scholar 

  • Albert M (1993) Neuropsychological and neurophysiological changes in healthy adult humans across the age range. Neurobiol Aging 14:623–625

    PubMed  CAS  Google Scholar 

  • Albin RL, Greenamyre JT (1992) Alternative excitotoxic hypotheses. Neurology 42:733–738

    PubMed  CAS  Google Scholar 

  • Arranz AM, Hussein A, Alix JJ, Perez-Cerda F, Allcock N, Matute C, Fern R (2008) Functional glutamate transport in rodent optic nerve axons and glia. Glia 56:1353–1367

    PubMed  Google Scholar 

  • Baltan S (2006) Surviving anoxia: a tale of two white matter tracts. Crit Rev Neurobiol 18:95–103

    PubMed  CAS  Google Scholar 

  • Baltan S (2009) Ischemic injury to white matter: an age-dependent process. Neuroscientist 15: 126–133

    PubMed  CAS  Google Scholar 

  • Baltan S (2012) Histone deacetylase inhibitors preserve function in aging axons. J Neurochem 123(suppl 2):108–115

    PubMed  CAS  Google Scholar 

  • Baltan Tekkök SB, Ransom BR (2004) Anoxia effects on CNS function and survival: regional differences. Neurochem Res 29:2163–2169

    Google Scholar 

  • Baltan Tekkök S, Brown AM, Ransom BR (2002) Persistence of axonal function during anoxia in mouse optic nerve. Glia S66

    Google Scholar 

  • Baltan S, Besancon EF, Mbow B, Ye Z, Hamner MA, Ransom BR (2008) White matter vulnerability to ischemic injury increases with age because of enhanced excitotoxicity. J Neurosci 28: 1479–1489

    PubMed  CAS  Google Scholar 

  • Baltan S, Bachleda A, Morrison RS, Murphy SP (2011a) Expression of histone deacetylases in cellular compartments of the mouse brain and the effects of ischemia. Transl Stroke Res 2:411–423

    PubMed  CAS  Google Scholar 

  • Baltan S, Murphy SP, Danilov CA, Bachleda A, Morrison RS (2011b) Histone deacetylase inhibitors preserve white matter structure and function during ischemia by conserving ATP and reducing excitotoxicity. J Neurosci 31:3990–3999

    PubMed  CAS  Google Scholar 

  • Barsoum MJ, Yuan H, Gerencser AA, Liot G, Kushnareva Y, Graber S, Kovacs I, Lee WD, Waggoner J, Cui J, White AD, Bossy B, Martinou JC, Youle RJ, Lipton SA, Ellisman MH, Perkins GA, Bossy-Wetzel E (2006) Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J 25:3900–3911

    PubMed  CAS  Google Scholar 

  • Basser PJ, Mattiello J, LeBihan D (1994) MR diffusion tensor spectroscopy and imaging. Biophys J 66:259–267

    PubMed  CAS  Google Scholar 

  • Bhat MA, Rios JC, Lu Y, Garcia-Fresco GP, Ching W, St Martin M, Li J, Einheber S, Chesler M, Rosenbluth J, Salzer JL, Bellen HJ (2001) Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin. Neuron 30:369–383

    PubMed  CAS  Google Scholar 

  • Black JA, Cummins TR, Plumpton C, Chen YH, Hormuzdiar W, Clare JJ, Waxman SG (1999) Upregulation of a silent sodium channel after peripheral, but not central, nerve injury in DRG neurons. J Neurophysiol 82:2776–2785

    PubMed  CAS  Google Scholar 

  • Boiko T, Rasband MN, Levinson SR, Caldwell JH, Mandel G, Trimmer JS, Matthews G (2001) Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron 30:91–104

    PubMed  CAS  Google Scholar 

  • Bonita R, Beaglehole R, Asplund K (1994) The worldwide problem of stroke. Curr Opin Neurol 7:5–10

    PubMed  CAS  Google Scholar 

  • Brand-Schieber E, Werner P (2003a) AMPA/kainate receptors in mouse spinal cord cell-specific display of receptor subunits by oligodendrocytes and astrocytes and at the nodes of Ranvier. Glia 42:12–24

    PubMed  Google Scholar 

  • Brand-Schieber E, Werner P (2003b) (+/−)-Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate receptor subunit expression in mouse versus rat spinal cord white matter: similarities in astrocytes but differences in oligodendrocytes. Neurosci Lett 345:126–130

    PubMed  CAS  Google Scholar 

  • Bristow EA, Griffiths PG, Andrews RM, Johnson MA, Turnbull DM (2002) The distribution of mitochondrial activity in relation to optic nerve structure. Arch Ophthalmol 120:791–796

    PubMed  Google Scholar 

  • Brown AM, Wender R, Ransom BR (2001) Metabolic substrates other than glucose support axon function in central white matter. J Neurosci Res 66:839–843

    PubMed  CAS  Google Scholar 

  • Campbell LW, Hao SY, Thibault O, Blalock EM, Landfield PW (1996) Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons. J Neurosci 16:6286–6295

    PubMed  CAS  Google Scholar 

  • Cavallotti C, Pacella E, Pescosolido N, Tranquilli-Leali FM, Feher J (2002) Age-related changes in the human optic nerve. Can J Ophthalmol 37:389–394

    PubMed  Google Scholar 

  • Cavallotti C, Cavallotti D, Pescosolido N, Pacella E (2003) Age-related changes in rat optic nerve: morphological studies. Anat Histol Embryol 32:12–16

    PubMed  CAS  Google Scholar 

  • Chang DT, Reynolds IJ (2006) Differences in mitochondrial movement and morphology in young and mature primary cortical neurons in culture. Neuroscience 141:727–736

    PubMed  CAS  Google Scholar 

  • Chen H, McCaffery JM, Chan DC (2007) Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130:548–562

    PubMed  CAS  Google Scholar 

  • Cheung EC, McBride HM, Slack RS (2007) Mitochondrial dynamics in the regulation of neuronal cell death. Apoptosis 12:979–992

    PubMed  Google Scholar 

  • Craner MJ, Hains BC, Lo AC, Black JA, Waxman SG (2004) Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain 127:294–303

    PubMed  Google Scholar 

  • Davatzikos C, Resnick SM (2002) Degenerative age changes in white matter connectivity visualized in vivo using magnetic resonance imaging. Cereb Cortex 12:767–771

    PubMed  Google Scholar 

  • Del Zoppo GJ (1995) Why do all drugs work in animals but none in stroke patients? 1. Drugs promoting cerebral blood flow. J Intern Med 237:79–88

    PubMed  Google Scholar 

  • Del Zoppo GJ (1998) Clinical trials in acute stroke: why have they not been successful? Neurology 51:S59–S61

    PubMed  Google Scholar 

  • Desilva TM, Billiards SS, Borenstein NS, Trachtenberg FL, Volpe JJ, Kinney HC, Rosenberg PA (2008) Glutamate transporter EAAT2 expression is up-regulated in reactive astrocytes in human periventricular leukomalacia. J Comp Neurol 508:238–248

    PubMed  CAS  Google Scholar 

  • Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397

    PubMed  CAS  Google Scholar 

  • Dupree JL, Girault JA, Popko B (1999) Axo-glial interactions regulate the localization of axonal paranodal proteins. J Cell Biol 147:1145–1152

    PubMed  CAS  Google Scholar 

  • Enblad P, Frykholm P, Valtysson J, Silander HC, Andersson J, Fasth KJ, Watanabe Y, Langstrom B, Hillered L, Persson L (2001) Middle cerebral artery occlusion and reperfusion in primates monitored by microdialysis and sequential positron emission tomography. Stroke 32: 1574–1580

    PubMed  CAS  Google Scholar 

  • Erecinska M, Silver IA (1994) Ions and energy in mammalian brain. Prog Neurobiol 43:37–71

    PubMed  CAS  Google Scholar 

  • Fern R, Moller T (2000) Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci 20:34–42

    PubMed  CAS  Google Scholar 

  • Fern R, Ransom BR (1997) Ischemic injury of optic nerve axons: the nuts and bolts. Clin Neurosci 4:246–250

    PubMed  CAS  Google Scholar 

  • Fern RJ, Hahm MS, Lu HK, Liu LP, Gorelick FS, Barrett PQ (1995) Ca2+/calmodulin-dependent protein kinase II activation and regulation of adrenal glomerulosa Ca2+ signaling. Am J Physiol 269:F751–F760

    PubMed  CAS  Google Scholar 

  • Ferro JM, Madureira S (2002) Age-related white matter changes and cognitive impairment. J Neurol Sci 203–204:221–225

    PubMed  Google Scholar 

  • Follett PL, Rosenberg PA, Volpe JJ, Jensen FE (2000) NBQX attenuates excitotoxic injury in developing white matter. J Neurosci 20:9235–9241

    PubMed  CAS  Google Scholar 

  • Foster RE, Connors BW, Waxman SG (1982) Rat optic nerve: electrophysiological, pharmacological and anatomical studies during development. Dev Brain Res 3:371–386

    Google Scholar 

  • Frykholm P, Andersson JL, Valtysson J, Silander HC, Hillered L, Persson L, Olsson Y, Yu WR, Westerberg G, Watanabe Y, Langstrom B, Enblad P (2000) A metabolic threshold of irreversible ischemia demonstrated by PET in a middle cerebral artery occlusion-reperfusion primate model. Acta Neurol Scand 102:18–26

    PubMed  CAS  Google Scholar 

  • Gadea A, Lopez-Colome AM (2001) Glial transporters for glutamate, glycine and GABA I. Glutamate transporters. J Neurosci Res 63:453–460

    PubMed  CAS  Google Scholar 

  • Gallo V, Russell JT (1995) Excitatory amino acid receptors in glia: different subtypes for distinct functions? J Neurosci Res 42:1–8

    PubMed  CAS  Google Scholar 

  • Garthwaite G, Brown G, Batchelor AM, Goodwin DA, Garthwaite J (1999) Mechanisms of ischaemic damage to central white matter axons: a quantitative histological analysis using rat optic nerve. Neuroscience 94:1219–1230

    PubMed  CAS  Google Scholar 

  • Ginsberg MD, Busto R (1989) Rodent models of cerebral ischemia. Stroke 20:1627–1642

    PubMed  CAS  Google Scholar 

  • Goldberg MP, Ransom BR (2003) New light on white matter. Stroke 34:330–332

    PubMed  Google Scholar 

  • Goldin AL, Barchi RL, Caldwell JH, Hofmann F, Howe JR, Hunter JC, Kallen RG, Mandel G, Meisler MH, Netter YB, Noda M, Tamkun MM, Waxman SG, Wood JN, Catterall WA (2000) Nomenclature of voltage-gated sodium channels. Neuron 28:365–368

    PubMed  CAS  Google Scholar 

  • Hachinski VC, Potter P, Merskey H (1987) Leuko-araiosis. Arch Neurol 44:21–23

    PubMed  CAS  Google Scholar 

  • Hazell AS, Rao KV, Danbolt NC, Pow DV, Butterworth RF (2001) Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernicke’s encephalopathy. J Neurochem 78:560–568

    PubMed  CAS  Google Scholar 

  • Hinman JD, Peters A, Cabral H, Rosene DL, Hollander W, Rasband MN, Abraham CR (2006) Age-related molecular reorganization at the node of Ranvier. J Comp Neurol 495:351–362

    PubMed  CAS  Google Scholar 

  • Hollenbeck PJ (2005) Mitochondria and neurotransmission: evacuating the synapse. Neuron 47: 331–333

    PubMed  CAS  Google Scholar 

  • Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118: 5411–5419

    PubMed  CAS  Google Scholar 

  • Jacquard C, Trioulier Y, Cosker F, Escartin C, Bizat N, Hantraye P, Cancela JM, Bonvento G, Brouillet E (2006) Brain mitochondrial defects amplify intracellular [Ca2+] rise and neurodegeneration but not Ca2+ entry during NMDA receptor activation. FASEB J 20:1021–1023

    PubMed  CAS  Google Scholar 

  • Jensen FE (2006) Developmental factors regulating susceptibility to perinatal brain injury and seizures. Curr Opin Pediatr 18:628–633

    PubMed  Google Scholar 

  • Karadottir R, Cavelier P, Bergersen LH, Attwell D (2005) NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438:1162–1166

    PubMed  CAS  Google Scholar 

  • Karbowski M, Youle RJ (2003) Dynamics of mitochondrial morphology in healthy cells and during apoptosis. Cell Death Differ 10:870–880

    PubMed  CAS  Google Scholar 

  • Karbowski M, Arnoult D, Chen H, Chan DC, Smith CL, Youle RJ (2004) Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis. J Cell Biol 164:493–499

    PubMed  CAS  Google Scholar 

  • Kawahara K, Kosugi T, Tanaka M, Nakajima T, Yamada T (2005) Reversed operation of glutamate transporter GLT-1 is crucial to the development of preconditioning-induced ischemic tolerance of neurons in neuron/astrocyte co-cultures. Glia 49:349–359

    PubMed  Google Scholar 

  • Kemper TL (1994) Neuroanatomical and neuropathological changes during aging and dementia. Oxford University Press, New York

    Google Scholar 

  • Kukley M, Capetillo-Zarate E, Dietrich D (2007) Vesicular glutamate release from axons in white matter. Nat Neurosci 10:311–320

    PubMed  CAS  Google Scholar 

  • Kurtzke JF (1994) Epidemiology of stroke: methods and trends. Health Rep 6:13–21

    PubMed  CAS  Google Scholar 

  • Landfield PW, Pitler TA (1984) Prolonged Ca2+−dependent after hyperpolarizations in hippocampal neurons of aged rats. Science 226:1089–1092

    PubMed  CAS  Google Scholar 

  • Lee L, Baltan Tekkok S, Deem S, Moulding J, Lam AM (2006) A novel model of in vivo pig posterior optic nerve ischemia. American Society of Anesthesiologists, Chicago, 14–17 Oct

    Google Scholar 

  • Leroux P, Hennebert C, Catteau J, Legros H, Hennebert O, Laudenbach V, Marret S (2010) Neuroprotective effects vary across nonsteroidal antiinflammatory drugs in a mouse model of developing excitotoxic brain injury. Neuroscience 167:716–723

    PubMed  CAS  Google Scholar 

  • Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL (2001) Mitochondrial dysfunction in cardiac disease: ischemia–reperfusion, aging, and heart failure. J Mol Cell Cardiol 33: 1065–1089

    PubMed  CAS  Google Scholar 

  • Li S, Mealing GA, Morley P, Stys PK (1999) Novel injury mechanism in anoxia and trauma of spinal cord white matter: glutamate release via reverse Na+-dependent glutamate transport. J Neurosci 19:RC1–RC9

    Google Scholar 

  • Longuemare MC, Rose CR, Farrell K, Ransom BR, Waxman SG, Swanson RA (1999) K(+)-induced reversal of astrocyte glutamate uptake is limited by compensatory changes in intracellular Na+. Neuroscience 93:285–292

    PubMed  CAS  Google Scholar 

  • Matute C, Alberdi E, Domercq M, Perez-Cerda F, Perez-Samartin A, Sanchez-Gomez MV (2001) The link between excitotoxic oligodendroglial death and demyelinating diseases. Trends Neurosci 24:224–230

    PubMed  CAS  Google Scholar 

  • McDonald JW, Althomsons SP, Hyrc KL, Choi DW, Goldberg MP (1998) Oligodendrocytes from forebrain are highly vulnerable to AMPA/kainate receptor-mediated excitotoxicity. Nat Med 4:291–297

    PubMed  CAS  Google Scholar 

  • Micu I, Jiang Q, Coderre E, Ridsdale A, Zhang L, Woulfe J, Yin X, Trapp BD, McRory JE, Rehak R, Zamponi GW, Wang W, Stys PK (2006) NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature 439:988–992

    PubMed  CAS  Google Scholar 

  • Misgeld T, Kerschensteiner M, Bareyre FM, Burgess RW, Lichtman JW (2007) Imaging axonal transport of mitochondria in vivo. Nat Methods 4:559–561

    PubMed  CAS  Google Scholar 

  • Morgan SC, Taylor DL, Pocock JM (2004) Microglia release activators of neuronal proliferation mediated by activation of mitogen-activated protein kinase, phosphatidylinositol-3-kinase/Akt and delta-Notch signalling cascades. J Neurochem 90:89–101

    PubMed  CAS  Google Scholar 

  • Mozdy AD, Shaw JM (2003) A fuzzy mitochondrial fusion apparatus comes into focus. Nat Rev Mol Cell Biol 4:468–478

    PubMed  CAS  Google Scholar 

  • Nicholls DG, Johnson-Cadwell L, Vesce S, Jekabsons M, Yadava N (2007) Bioenergetics of mitochondria in cultured neurons and their role in glutamate excitotoxicity. J Neurosci Res 85:3206–3212

    PubMed  CAS  Google Scholar 

  • O’Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467–477

    PubMed  Google Scholar 

  • O’Sullivan M, Jones DK, Summers PE, Morris RG, Williams SC, Markus HS (2001) Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 57: 632–638

    PubMed  Google Scholar 

  • Oberheim NA, Tian GF, Han X, Peng W, Takano T, Ransom B, Nedergaard M (2008) Loss of astrocytic domain organization in the epileptic brain. J Neurosci 28:3264–3276

    PubMed  CAS  Google Scholar 

  • Ogura K, Ogawa M, Yoshida M (1994) Effects of ageing on microglia in the normal rat brain: immunohistochemical observations. Neuroreport 5:1224–1226

    PubMed  CAS  Google Scholar 

  • Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ (1993) Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms, and prevention. J Neurosci 13:1441–1453

    PubMed  CAS  Google Scholar 

  • Olivares R, Montiel J, Aboitiz F (2001) Species differences and similarities in the fine structure of the mammalian corpus callosum. Brain Behav Evol 57:98–105

    PubMed  CAS  Google Scholar 

  • Otsuga D, Keegan BR, Brisch E, Thatcher JW, Hermann GJ, Bleazard W, Shaw JM (1998) The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J Cell Biol 143:333–349

    PubMed  CAS  Google Scholar 

  • Ouardouz M, Nikolaeva MA, Coderre E, Zamponi GW, McRory JE, Trapp BD, Yin X, Wang W, Woulfe J, Stys PK (2003) Depolarization-induced Ca2+ release in ischemic spinal cord white matter involves L-type Ca2+ channel activation of ryanodine receptors. Neuron 40:53–63

    PubMed  CAS  Google Scholar 

  • Ouardouz M, Malek S, Coderre E, Stys PK (2006) Complex interplay between glutamate receptors and intracellular Ca2+ stores during ischaemia in rat spinal cord white matter. J Physiol 577:191–204

    PubMed  CAS  Google Scholar 

  • Pantoni L, Garcia JH, Gutierrez JA (1996) Cerebral white matter is highly vulnerable to ischemia. Stroke 27:1641–1646; discussion 1647

    PubMed  CAS  Google Scholar 

  • Parihar MS, Brewer GJ (2007) Simultaneous age-related depolarization of mitochondrial membrane potential and increased mitochondrial reactive oxygen species production correlate with age-related glutamate excitotoxicity in rat hippocampal neurons. J Neurosci Res 85: 1018–1032

    PubMed  CAS  Google Scholar 

  • Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747

    PubMed  CAS  Google Scholar 

  • Pendlebury ST, Blamire AM, Lee MA, Styles P, Matthews PM (1999) Axonal injury in the internal capsule correlates with motor impairment after stroke. Stroke 30:956–962

    PubMed  CAS  Google Scholar 

  • Peters A, Sethares C (1993) Aging and the Meynert cells in rhesus monkey primary visual cortex. Anat Rec 236:721–729

    PubMed  CAS  Google Scholar 

  • Rintoul GL, Filiano AJ, Brocard JB, Kress GJ, Reynolds IJ (2003) Glutamate decreases mitochondrial size and movement in primary forebrain neurons. J Neurosci 23:7881–7888

    PubMed  CAS  Google Scholar 

  • Romera C, Hurtado O, Botella SH, Lizasoain I, Cardenas A, Fernandez-Tome P, Leza JC, Lorenzo P, Moro MA (2004) In vitro ischemic tolerance involves upregulation of glutamate transport partly mediated by the TACE/ADAM17-tumor necrosis factor-alpha pathway. J Neurosci 24: 1350–1357

    PubMed  CAS  Google Scholar 

  • Rothman SM, Olney JW (1995) Excitotoxicity and the NMDA receptor–still lethal after eight years. Trends Neurosci 18:57–58

    PubMed  CAS  Google Scholar 

  • Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, Welty DF (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686

    PubMed  CAS  Google Scholar 

  • Saab A, Baltan S, Möbius I, Tzvetavona J, Hirrlinger B, Goetze HM, Jahn W, Huang A, Pérez-Samartín F, Pérez-Cerdá C, Matute S, Löwel K-A, Nave F, Kirchhoff (2012) Oligodendroglial NMDA receptor signalling in coupling axonal and glial energy metabolism. Society for Neuroscience Abstracts, New Orleans, LA

    Google Scholar 

  • Salter MG, Fern R (2005) NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438:1167–1171

    PubMed  CAS  Google Scholar 

  • Sanchez-Gomez MV, Matute C (1999) AMPA and kainate receptors each mediate excitotoxicity in oligodendroglial cultures. Neurobiol Dis 6:475–485

    PubMed  CAS  Google Scholar 

  • Scavone C, Munhoz CD, Kawamoto EM, Glezer I, de Sa LL, Marcourakis T, Markus RP (2005) Age-related changes in cyclic GMP and PKG-stimulated cerebellar Na, K-ATPase activity. Neurobiol Aging 26:907–916

    PubMed  CAS  Google Scholar 

  • Schmidt R, Fazekas F, Offenbacher H, Lytwyn H, Blematl B, Niederkorn K, Horner S, Payer F, Freidl W (1991) Magnetic resonance imaging white matter lesions and cognitive impairment in hypertensive individuals. Arch Neurol 48:417–420

    PubMed  CAS  Google Scholar 

  • Scott SV, Cassidy-Stone A, Meeusen SL, Nunnari J (2003) Staying in aerobic shape: how the structural integrity of mitochondria and mitochondrial DNA is maintained. Curr Opin Cell Biol 15:482–488

    PubMed  CAS  Google Scholar 

  • Selzner M, Selzner N, Jochum W, Graf R, Clavien PA (2007) Increased ischemic injury in old mouse liver: an ATP-dependent mechanism. Liver Transpl 13:382–390

    PubMed  Google Scholar 

  • Silva-Adaya D, Perez-De La Cruz V, Herrera-Mundo MN, Mendoza-Macedo K, Villeda-Hernandez J, Binienda Z, Ali SF, Santamaria A (2008) Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of L-carnitine. J Neurochem 105:677–689

    PubMed  CAS  Google Scholar 

  • Sloane JA, Hollander W, Moss MB, Rosene DL, Abraham CR (1999) Increased microglial activation and protein nitration in white matter of the aging monkey. Neurobiol Aging 20:395–405

    PubMed  CAS  Google Scholar 

  • Smirnova E, Shurland DL, Ryazantsev SN, van der Bliek AM (1998) A human dynamin-related protein controls the distribution of mitochondria. J Cell Biol 143:351–358

    PubMed  CAS  Google Scholar 

  • 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: 261–272

    PubMed  Google Scholar 

  • Stys PK (2004) White matter injury mechanisms. Curr Mol Med 4:113–130

    PubMed  CAS  Google Scholar 

  • Stys PK, Ransom BR, Waxman SG, Davis PK (1990) Role of extracellular calcium in anoxic injury of mammalian central white matter. Proc Natl Acad Sci U S A 87:4212–4216

    PubMed  CAS  Google Scholar 

  • Stys PK, Waxman SG, Ransom BR (1992) Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na+-Ca2+ exchanger. J Neurosci 12:430–439

    PubMed  CAS  Google Scholar 

  • Szabadkai G, Rizzuto R (2004) Participation of endoplasmic reticulum and mitochondrial calcium handling in apoptosis: more than just neighborhood? FEBS Lett 567:111–115

    PubMed  CAS  Google Scholar 

  • Szabadkai G, Simoni AM, Chami M, Wieckowski MR, Youle RJ, Rizzuto R (2004) Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+−mediated apoptosis. Mol Cell 16:59–68

    PubMed  CAS  Google Scholar 

  • Szatkowski M, Barbour B, Attwell D (1990) Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature 348:443–446

    PubMed  CAS  Google Scholar 

  • Tekkök SB, Goldberg MP (2001) Ampa/kainate receptor activation mediates hypoxic oligodendrocyte death and axonal injury in cerebral white matter. J Neurosci 21:4237–4248

    PubMed  Google Scholar 

  • Tekkok SB, Brown AM, Ransom BR (2003) Axon function persists during anoxia in mammalian white matter. J Cereb Blood Flow Metab 23:1340–1347

    PubMed  Google Scholar 

  • Tekkok SB, Ye Z, Ransom BR (2007) Excitotoxic mechanisms of ischemic injury in myelinated white matter. J Cereb Blood Flow Metab 27:1540–1552

    PubMed  Google Scholar 

  • Thorell WE, Leibrock LG, Agrawal SK (2002) Role of RyRs and IP3 receptors after traumatic injury to spinal cord white matter. J Neurotrauma 19:335–342

    PubMed  CAS  Google Scholar 

  • Toescu EC (2005) Normal brain ageing: models and mechanisms. Philos Trans R Soc Lond B Biol Sci 360:2347–2354

    PubMed  CAS  Google Scholar 

  • Ture D, Yasargil MG, Krist AF (1996) The arteries of the corpus callosum: a microsurgical anatomic study. Neurosurgery 39:1075–1085

    PubMed  CAS  Google Scholar 

  • Underhill SM, Goldberg MP (2007) Hypoxic injury of isolated axons is independent of ionotropic glutamate receptors. Neurobiol Dis 25:284–290

    PubMed  CAS  Google Scholar 

  • Uo T, Dworzak J, Kinoshita C, Inman DM, Kinoshita Y, Horner PJ, Morrison RS (2009) Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons. Exp Neurol 218:274–285

    PubMed  CAS  Google Scholar 

  • Verkhratsky A, Orkand RK, Kettenmann H (1998) Glial calcium: homeostasis and signaling function. Physiol Rev 78:99–141

    PubMed  CAS  Google Scholar 

  • Vincent SL, Peters A, Tigges J (1989) Effects of aging on the neurons within area 17 of rhesus monkey cerebral cortex. Anat Rec 223:329–341

    PubMed  CAS  Google Scholar 

  • Wolf JA, Stys PK, Lusardi T, Meaney D, Smith DH (2001) Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels. J Neurosci 21: 1923–1930

    PubMed  CAS  Google Scholar 

  • Wolfram-Gabel R, Maillot C, Koritke JG, Laude M (1987) [The vascularization of the human tela choroidea of the lateral ventricle]. Acta Anat (Basel) 128:301–321

    CAS  Google Scholar 

  • Wrathall JR, Choiniere D, Teng YD (1994) Dose-dependent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainate antagonist NBQX. J Neurosci 14:6598–6607

    PubMed  CAS  Google Scholar 

  • Yamauchi H, Fukuda H, Oyanagi C (2002) Significance of white matter high intensity lesions as a predictor of stroke from arteriolosclerosis. J Neurol Neurosurg Psychiatry 72:576–582

    PubMed  CAS  Google Scholar 

  • Ye ZC, Wyeth MS, Baltan-Tekkok S, Ransom BR (2003) Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J Neurosci 23:3588–3596

    PubMed  CAS  Google Scholar 

  • Zhang K, Sejnowski TJ (2000) A universal scaling law between gray matter and white matter of cerebral cortex. Proc Natl Acad Sci U S A 97:5621–5626

    PubMed  CAS  Google Scholar 

  • Zhang M, Li WB, Geng JX, Li QJ, Sun XC, Xian XH, Qi J, Li SQ (2007) The upregulation of glial glutamate transporter-1 participates in the induction of brain ischemic tolerance in rats. J Cereb Blood Flow Metab 27:1352–1368

    PubMed  CAS  Google Scholar 

  • Ziskin JL, Nishiyama A, Rubio M, Fukaya M, Bergles DE (2007) Vesicular release of glutamate from unmyelinated axons in white matter. Nat Neurosci 10:321–330

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

 The studies from the author’s laboratory that are described in this chapter were supported by National Institutes of Health/National Institute of Aging grant R01AG033720.

Author information

Authors and Affiliations

  1. Department of Neurosciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA

    Selva Baltan

Authors
  1. Selva Baltan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Selva Baltan .

Editor information

Editors and Affiliations

  1. Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA

    Selva Baltan

  2. Department of Neurology, University of California, Los Angeles, Los Angeles, California, USA

    S. Thomas Carmichael

  3. Departamento de Neurociencias, Achucarro Basque Centger for Neuroscience, University del Pais Vasco (UPV/EHU), and Centro de, Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Leioa, Spain

    Carlos Matute

  4. University of Michigan Dept. Neurosurgery, Ann Arbor, Michigan, USA

    Guohua Xi

  5. Dept. Pharmacology Dept. Neurosurgery, Loma Linda University Dept. Physiology, Loma Linda, California, USA

    John H Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Baltan, S. (2014). Age-Dependent Mechanisms of White Matter Injury After Stroke. In: Baltan, S., Carmichael, S., Matute, C., Xi, G., Zhang, J. (eds) White Matter Injury in Stroke and CNS Disease. Springer Series in Translational Stroke Research, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9123-1_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-9123-1_16

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-9122-4

  • Online ISBN: 978-1-4614-9123-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation