Skip to main content
SpringerLink
Log in

Acute Axonal Injury in White Matter Stroke

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

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

  • 1430 Accesses

Abstract

Stroke is a leading cause of death and disability. Thrombolysis and revascularization have greatly enhanced our ability to treat acute strokes secondary to large vessel occlusions. Despite these advances, stroke due to small vessel disease remains an important clinical problem accounting for up to 25 % of the 795,000 new strokes occurring annually in the USA. The vast majority of these small vessel infarcts affect brain white matter, resulting in focal myelin loss and axonal degeneration that produces physical and mental disability. There is also increasing evidence that repeated small vessel infarcts within the white matter increase the risk of large vessel cortical strokes and may place patients at risk for the development of vascular dementia.

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

  • Bartsch U, Montag D et al (1995) Multiply myelinated axons in the optic nerve of mice deficient for the myelin-associated glycoprotein. Glia 14(2):115–122

    Article  PubMed  CAS  Google Scholar 

  • Ben-Tov Perry R, Doron-Mandel E et al (2012) Subcellular knockout of importin beta1 perturbs axonal retrograde signaling. Neuron 75(2):294–305

    Article  Google Scholar 

  • Ben-Yaakov K, Dagan SY et al (2012) Axonal transcription factors signal retrogradely in lesioned peripheral nerve. EMBO J 31(6):1350–1363

    Google Scholar 

  • Bhat MA, Rios JC et al (2001) Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin. Neuron 30(2):369–383

    Article  PubMed  CAS  Google Scholar 

  • Blanco M, Lizasoain I et al (2006) Ischemic preconditioning: a novel target for neuroprotective therapy. Cerebrovasc Dis 21(suppl 2):38–47

    Article  PubMed  CAS  Google Scholar 

  • Bokura H, Yamaguchi S et al (2008) Metabolic syndrome is associated with silent ischemic brain lesions. Stroke 39(5):1607–1609

    Article  PubMed  Google Scholar 

  • Boyle ME, Berglund EO et al (2001) Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve. Neuron 30(2):385–397

    Article  PubMed  CAS  Google Scholar 

  • Brailowsky S, Knight RT et al (1986) Gamma-aminobutyric acid-induced potentiation of cortical hemiplegia. Brain Res 362(2):322–330

    Article  PubMed  CAS  Google Scholar 

  • Bray GM, Duncan ID et al (1983) ‘Shaking pups’: a disorder of central myelination in the spaniel dog. IV. Freeze-fracture electron microscopic studies of axons, oligodendrocytes and astrocytes in the spinal cord white matter. Neuropathol Appl Neurobiol 9(5):369–378

    Article  PubMed  CAS  Google Scholar 

  • Calabrese M, Rinaldi F et al (2010) Widespread cortical thinning characterizes patients with MS with mild cognitive impairment. Neurology 74(4):321–328

    Article  PubMed  CAS  Google Scholar 

  • Carmichael ST (2006) Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol 59(5):735–742

    Article  PubMed  CAS  Google Scholar 

  • Carmichael ST (2008) Themes and strategies for studying the biology of stroke recovery in the poststroke epoch. Stroke 39(4):1380–1388

    Article  PubMed  Google Scholar 

  • Carmichael ST, Chesselet MF (2002) Synchronous neuronal activity is a signal for axonal sprouting after cortical lesions in the adult. J Neurosci 22(14):6062–6070

    PubMed  CAS  Google Scholar 

  • Carmichael ST, Archibeque I et al (2005) Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex. Exp Neurol 193(2):291–311

    Article  PubMed  CAS  Google Scholar 

  • Cheng HC, Burke RE (2010) The Wld(S) mutation delays anterograde, but not retrograde, axonal degeneration of the dopaminergic nigro-striatal pathway in vivo. J Neurochem 113(3):683–691

    Article  PubMed  CAS  Google Scholar 

  • Chin Y, Sato Y et al (2010) Transient decrease in cerebral motor pathway fractional anisotropy after focal ischemic stroke in monkey. Neurosci Res 66:406–411

    Article  PubMed  Google Scholar 

  • Clarkson AN, Huang BS et al (2010) Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature 468(7321):305–309

    Article  PubMed  CAS  Google Scholar 

  • Comelli MC, Seren MS et al (1992) Photochemical stroke and brain-derived neurotrophic factor (BDNF) mRNA expression. Neuroreport 3(6):473–476

    Article  PubMed  CAS  Google Scholar 

  • Cook DJ, Tymianski M (2011) Translating promising preclinical neuroprotective therapies to human stroke trials. Expert Rev Cardiovasc Ther 9(4):433–449

    Article  PubMed  Google Scholar 

  • De Ryck M, Duytschaever H et al (1990) Ionic channels, cholinergic mechanisms, and recovery of sensorimotor function after neocortical infarcts in rats. Stroke 21(11 suppl):III158–III163

    PubMed  Google Scholar 

  • Dufouil C, Godin O et al (2009) Severe cerebral white matter hyperintensities predict severe cognitive decline in patients with cerebrovascular disease history. Stroke 40(6):2219–2221

    Article  PubMed  Google Scholar 

  • Dupree JL, Girault JA et al (1999) Axo-glial interactions regulate the localization of axonal paranodal proteins. J Cell Biol 147(6):1145–1152

    Article  PubMed  CAS  Google Scholar 

  • Fu Y, Sun W et al (2009) Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction. PLoS One 4(8):e6705

    Article  PubMed  Google Scholar 

  • Gary DS, Malone M et al (2012) Electrical stimulation promotes the survival of oligodendrocytes in mixed cortical cultures. J Neurosci Res 90(1):72–83

    Article  PubMed  CAS  Google Scholar 

  • Gouw AA, van der Flier WM et al (2008a) Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study. Stroke 39(5):1414–1420

    Article  PubMed  Google Scholar 

  • Gouw AA, van der Flier WM et al (2008b) On the etiology of incident brain lacunes: longitudinal observations from the LADIS study. Stroke 39(11):3083–3085

    Article  PubMed  Google Scholar 

  • Gusev EI, Skvortsova VI (2003) Brain ischemia. Springer, Berlin

    Book  Google Scholar 

  • Ha GK, Parikh S et al (2008) Influence of injury severity on the rate and magnitude of the T lymphocyte and neuronal response to facial nerve axotomy.199(1-2):18–23

    Google Scholar 

  • Hinman JD, Peters A et al (2006) Age-related molecular reorganization at the node of Ranvier. J Comp Neurol 495(4):351–362

    Article  PubMed  CAS  Google Scholar 

  • Howell OW, Palser A et al (2006) Disruption of neurofascin localization reveals early changes preceding demyelination and remyelination in multiple sclerosis. Brain 129(pt 12):3173–3185

    Article  PubMed  CAS  Google Scholar 

  • Hughes PM, Anthony DC et al (2003) Focal lesions in the rat central nervous system induced by endothelin-1. J Neuropathol Exp Neurol 62(12):1276–1286

    PubMed  CAS  Google Scholar 

  • Hydman J, Svensson M et al (2005) Neuronal survival and glial reactions after recurrent laryngeal nerve resection in the rat. Laryngoscope 115(4):619–624

    Google Scholar 

  • Inzitari D, Pracucci G et al (2009) Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort. BMJ 339:b2477

    Article  PubMed  Google Scholar 

  • Kee NJ, Preston E et al (2001) Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. Exp Brain Res 136(3):313–320

    Article  PubMed  CAS  Google Scholar 

  • Kenney AM, and Kocsis JD (1998) Peripheral axotomy induces long-term c-jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia In vivo. 18(4):1318–1328

    Google Scholar 

  • Kilic E, ElAli A et al (2010) Role of Nogo-A in neuronal survival in the reperfused ischemic brain. J Cereb Blood Flow Metab 30(5):969–984

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi S, Okada K et al (1997) Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke 28(10):1932–1939

    Article  PubMed  CAS  Google Scholar 

  • Koch S, McClendon MS et al (2011) Imaging evolution of acute lacunar infarction: leukoariosis or lacune? Neurology 77(11):1091–1095

    Article  PubMed  Google Scholar 

  • Kumami K, Mrsulja BB et al (1988) Effect of ischemia on noradrenergic and energy-related metabolites in the cerebral cortex of young and adult gerbils. Metab Brain Dis 3(4):273–277

    Article  PubMed  CAS  Google Scholar 

  • Kurek JB, Austin L et al (1996) Up-regulation of leukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and muscle following denervation. 6(2):105–114

    Google Scholar 

  • Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, Liu Y, Tsingalia A, Jin L, Zhang PW, Pellerin L, Magistretti PJ, Rothstein JD (2012) Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487(7408):443–448

    Google Scholar 

  • Lee N, Neitzel KL, et al (2004) STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: potential role for STAT3 as a retrograde signaling transcription factor. 474(4):535–545

    Google Scholar 

  • Li S, Carmichael ST (2006) Growth-associated gene and protein expression in the region of axonal sprouting in the aged brain after stroke. Neurobiol Dis 23(2):362–373

    Article  PubMed  CAS  Google Scholar 

  • Liao D, Cooper L et al (1996) Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Atherosclerosis Risk in Communities Study. Stroke 27(12):2262–2270

    Article  PubMed  CAS  Google Scholar 

  • Lindwall C, Dahlin L, et al (2004) Inhibition of c-jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons.27(3):267–279

    Google Scholar 

  • Lindwall C and Kanje M (2005) Retrograde axonal transport of JNK signaling molecules influence injury induced nuclear changes in p-c-jun and ATF3 in adult rat sensory neurons.29(2):269–282

    Google Scholar 

  • Mack TG, Reiner M et al (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci 4(12):1199–1206

    Article  PubMed  CAS  Google Scholar 

  • Maillard P, Fletcher E et al (2011) White matter hyperintensity penumbra. Stroke 42(7):1917–1922

    Article  PubMed  Google Scholar 

  • Mattson MP, Gleichmann M et al (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60(5):748–766

    Article  PubMed  CAS  Google Scholar 

  • Matute C (2006) Oligodendrocyte NMDA receptors: a novel therapeutic target. Trends Mol Med 12(7):289–292

    Article  PubMed  CAS  Google Scholar 

  • Matute C (2010) Calcium dyshomeostasis in white matter pathology. Cell Calcium 47(2):150–157

    Article  PubMed  CAS  Google Scholar 

  • Matute C, Alberdi E et al (2007a) Excitotoxic damage to white matter. J Anat 210(6):693–702

    Article  PubMed  CAS  Google Scholar 

  • Matute C, Torre I et al (2007b) P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. J Neurosci 27(35):9525–9533

    Article  PubMed  CAS  Google Scholar 

  • McIver SR, Muccigrosso M et al (2010) Oligodendrocyte degeneration and recovery after focal cerebral ischemia. Neuroscience 169(3):1364–1375

    Article  PubMed  CAS  Google Scholar 

  • McTigue DM, Tripathi RB (2008) The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem 107(1):1–19

    Article  PubMed  CAS  Google Scholar 

  • Mesnard NA, Alexander TD et al (2010) Use of laser microdissection in the investigation of facial motoneuron and neuropil molecular phenotypes after peripheral axotomy.225(1):94–103

    Google Scholar 

  • Murphy PG, Borthwick LS et al (1999) Nature of the retrograde signal from injured nerves that induces interleukin-6 mRNA in neurons.19(10):3791–3800

    Google Scholar 

  • Papadopoulos CM, Tsai SY et al (2009) Motor recovery and axonal plasticity with short-term amphetamine after stroke. Stroke 40(1):294–302

    Article  PubMed  CAS  Google Scholar 

  • Pillai AM, Thaxton C et al (2009) Spatiotemporal ablation of myelinating glia-specific neurofascin (Nfasc NF155) in mice reveals gradual loss of paranodal axoglial junctions and concomitant disorganization of axonal domains. J Neurosci Res 87(8):1773–1793

    Article  PubMed  CAS  Google Scholar 

  • Pomeroy IM, Jordan EK et al (2008) Diffuse cortical atrophy in a marmoset model of multiple sclerosis. Neurosci Lett 437(2):121–124

    Article  PubMed  CAS  Google Scholar 

  • Rasband MN, Peles E et al (1999) Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS. J Neurosci 19(17):7516–7528

    PubMed  CAS  Google Scholar 

  • Rasband MN, Kagawa T et al (2003) Dysregulation of axonal sodium channel isoforms after adult-onset chronic demyelination. J Neurosci Res 73(4):465–470

    Article  PubMed  CAS  Google Scholar 

  • Reimer MM, McQueen J et al (2011) Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion. J Neurosci 31(49):18185–18194

    Article  PubMed  CAS  Google Scholar 

  • Richardson PM, Miao T et al (2009) Responses of the nerve cell body to a xotomy. Neurosurgery 65(4 Suppl): A74–79

    Article  PubMed  Google Scholar 

  • Roger VL, Go AS et al (2012) Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation 125(1):e2–e220

    Article  PubMed  Google Scholar 

  • Rosenberg GA (2009) Inflammation and white matter damage in vascular cognitive impairment. Stroke 40(3 suppl):S20–S23

    Article  PubMed  Google Scholar 

  • Rost NS, Fitzpatrick K et al (2010) White matter hyperintensity burden and susceptibility to cerebral ischemia. Stroke 41(12):2807–2811

    Article  PubMed  Google Scholar 

  • Sahathevan R, Brodtmann A et al (2012) Dementia, stroke, and vascular risk factors: a review. Int J Stroke 7(1):61–73

    Article  PubMed  Google Scholar 

  • Sailer M, Fischl B et al (2003) Focal thinning of the cerebral cortex in multiple sclerosis. Brain 126(pt 8):1734–1744

    Article  PubMed  Google Scholar 

  • Schwartz GL, Fornage M et al (2005) Treatment of leukoaraiosis. Curr Treat Options Cardiovasc Med 7(3):173–177

    Article  PubMed  Google Scholar 

  • Seo SW, Lee JM et al (2012a) Cortical thinning related to periventricular and deep white matter hyperintensities. Neurobiol Aging 33(7):1156–1167

    Article  PubMed  Google Scholar 

  • Seo SW, Lee JM et al (2012b) Cardiovascular risk factors cause cortical thinning in cognitively impaired patients: relationships among cardiovascular risk factors, white matter hyperintensities, and cortical atrophy. Alzheimer Dis Assoc Disord 26(2):106–112

    Article  PubMed  Google Scholar 

  • Shepherd MN, Pomicter AD et al (2012) Paranodal reorganization results in the depletion of transverse bands in the aged central nervous system. Neurobiol Aging 33(1):203.e13–24

    Article  Google Scholar 

  • Shin JE, Cho Y et al (2012) Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron 74(6):1015–1022

    Article  PubMed  CAS  Google Scholar 

  • Silbert LC, Dodge HH et al (2012) Trajectory of white matter hyperintensity burden preceding mild cognitive impairment. Neurology 79(8):741–747

    Article  PubMed  Google Scholar 

  • Sozmen EG, Kolekar A et al (2009) A white matter stroke model in the mouse: axonal damage, progenitor responses and MRI correlates. J Neurosci Methods 180(2):261–272

    Article  PubMed  Google Scholar 

  • Sozmen EG, Hinman JD et al (2012) Models that matter: white matter stroke models. Neurotherapeutics 9(2):349–358

    Article  PubMed  Google Scholar 

  • Taveggia C, Feltri ML et al (2010) Signals to promote myelin formation and repair. Nat Rev Neurol 6(5):276–287

    Article  PubMed  Google Scholar 

  • Teigler A, Komljenovic D et al (2009) Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum. Hum Mol Genet 18(11):1897–1908

    Article  PubMed  CAS  Google Scholar 

  • Tonra JR, Curtis R et al (1998) Axotomy upregulates the anterograde transport and expression of brain-derived neurotrophic factor by sensory neurons.18(11):4374–4383

    Google Scholar 

  • Vosler PS, Brennan CS et al (2008) Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol Neurobiol 38(1):78–100

    Article  PubMed  CAS  Google Scholar 

  • Wake H, Lee PR et al (2011) Control of local protein synthesis and initial events in myelination by action potentials. Science 333(6049):1647–1651

    Article  PubMed  CAS  Google Scholar 

  • Wang J, He Z (2009) NAD and axon degeneration: from the Wlds gene to neurochemistry. Cell Adh Migr 3(1):77–87

    Article  PubMed  Google Scholar 

  • Wang J, Zhai Q et al (2005) A local mechanism mediates NAD-dependent protection of axon degeneration. J Cell Biol 170(3):349–355

    Article  PubMed  CAS  Google Scholar 

  • Wiley-Livingston CA, Ellisman MH (1981) Myelination-dependent axonal membrane specializations demonstrated in insufficiently myelinated nerves of the dystrophic mouse. Brain Res 224(1):55–67

    Article  PubMed  CAS  Google Scholar 

  • Wingerchuk DM, Lucchinetti CF et al (2001) Multiple sclerosis: current pathophysiological concepts. Lab Invest 81(3):263–281

    Article  PubMed  CAS  Google Scholar 

  • Xiong YY, Mok V (2011) Age-related white matter changes. J Aging Res 2011:617927

    PubMed  Google Scholar 

  • Xu JJ, Chen EY et al (2009) Recombinant ciliary neurotrophic factor promotes nerve regeneration and induces gene expression in silicon tube-bridged transected sciatic nerves in adult rats. 16(6):812–817

    Google Scholar 

  • Yoshimura K, Ueno M et al (2011) c-jun N-terminal kinase induces axonal egeneration and limits motor recovery after spinal cord injury in mice.”71(3):266–277

    Google Scholar 

  • Zhuang L, Sachdev PS et al (2012) Microstructural white matter changes in cognitively normal individuals at risk of amnestic MCI. Neurology 79(8):748–754

    Article  PubMed  Google Scholar 

  • Zhuo PH, Xiong Y et al (2007) Expression of bcl-2 protein and apoptosis of neurocytes in neonatal rats with brain white matter damage. Zhongguo Dang Dai Er Ke Za Zhi 9(2):164–168

    PubMed  CAS  Google Scholar 

  • Zigmond RE (2011) gp130 cytokines are positive signals triggering changes in gene expression and axon outgrowth in peripheral neurons following injury. Front Mol Neurosci 4:62

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA

    Jason D. Hinman & S. Thomas Carmichael M.D.

Authors
  1. Jason D. Hinman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Thomas Carmichael M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Thomas Carmichael M.D. .

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

Hinman, J.D., Carmichael, S.T. (2014). Acute Axonal Injury in White Matter 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_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-9123-1_21

  • 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