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Cortical spreading depression (CSD)

Ein neurophysiologisches Korrelat der Migräneaura

Cortical spreading depression (CSD)

A neurophysiological correlate of migraine aura

Der Schmerz volume 22, pages 544–550 (2008)Cite this article

Zusammenfassung

Die „cortical spreading depression“ (CSD) ist eine transiente (60–120 s) Depolarisation der Nerven- und Gliazellen der Hirnrinde (Verschiebung des kortikalen Gleichspannungspotenzials um 20–35 mV), die sich mit 3–5 mm/min über die Kortexhemisphäre ausbreitet. Während der CSD kommt es zu massiven Umverteilungen von Ionen zwischen dem Extra- und Intrazellulärraum sowie einem Wassereinstrom in die Zellen. Die extrazelluläre Kaliumionenkonzentration kann dabei bis auf 60 mM/l ansteigen. Kaliumionen und die exzitatorische Aminosäure Glutamat sind wesentlich an der Entstehung und Ausbreitung der CSD beteiligt. Sowohl die Depolarisation als auch die temporäre Störung der ionalen Homöostase sind regenerativ und verbrauchen bei der Restitution Energie, schädigen aber normal perfundiertes Hirngewebe nicht. Die gleiche Ausbreitungsgeschwindigkeit von CSD und Skotomen in der Migräneaura hat seit langem die Meinung gestützt, dass die CSD das Korrelat der Migräneaura sein soll. Seit der Beobachtung von CSD-ähnlichen Vorgängen bei Patienten während der Migräneaura im Magnetenzephalogramm (MEG) ist dieser Zusammenhang sehr wahrscheinlich geworden. Die Rolle der CSD als Verursacher des Migränekopfschmerzes ist dagegen umstritten.

Abstract

Cortical spreading depression (CSD) is a transient (60–120 s) and at 3–5 mm/min propagating depolarization wave of cortical neurons and glial cells and is characterized by a DC shift of 20–35 mV. It is accompanied by massive redistribution of ions between extracellular and intracellular compartments and by a water influx into the cells. Extracellular potassium ion concentration increases up to 60 mM/l. Potassium ions and the excitatory neurotransmitter glutamate essentially contribute to the initiation and propagation of CSD. Both depolarization and disturbance of brain ion homeostasis regenerate within a few minutes while enhancing energy metabolism, but do not cause damage to normally perfused brain tissue. The similar propagation velocity of CSD and visual scotoma during migraine aura led to the assumption that CSD could be the underlying mechanism of migraine aura. The observation of CSD waves in migraine aura patients with the magnet encephalogram (MEG) technique confirmed this theory. Although many data support the relationship between CSD and aura phase in migraine, the role of CSD in migraine headache is still disputed.

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Literatur

  1. Ambrosini A, Schoenen J (2003) The electrophysiology of migraine. Curr Opin Neurol 16: 327–331

    Article  PubMed  Google Scholar 

  2. Antal A, Temme J, Nitsche MA et al. (2005) Altered motion perception in migraineurs: evidence for interictal cortical hyperexcitability. Cephalalgia 25: 788–794

    Article  PubMed  CAS  Google Scholar 

  3. Aurora SK, Ahmad BK, Welch KM et al. (1998)Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine. Neurology 50: 1111–1114

    PubMed  CAS  Google Scholar 

  4. Ayata C, Shimizu-Sasamata M, Lo EH et al. (2000) Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha1A subunit of P/Q type calcium channels. Neuroscience 95: 639–645

    Article  PubMed  CAS  Google Scholar 

  5. Bahra A, Matharu MS, Buchel C et al. (2001) Brainstem activation specific to migraine headache. Lancet 357: 1016–1017

    Article  PubMed  CAS  Google Scholar 

  6. Bolay H, Reuter U, Dunn AK et al. (2002) Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 8: 136–142

    Article  PubMed  CAS  Google Scholar 

  7. Bowyer SM, Aurora KS, Moran JE et al. (2001) Magnetoencephalographic fields from patients with spontaneous and induced migraine aura. Ann Neurol 50: 582–587

    Article  PubMed  CAS  Google Scholar 

  8. Bureš J, Burešova O, Křivanek J (eds) (1974) The mechanism and applications of Leão’s spreading depression of electroencephalographic activity. Academia, Prague

  9. Cairns BE (2007) The influence of gender and sex steroids on craniofacial nociception. Headache 47: 319–324

    Article  PubMed  Google Scholar 

  10. Colonna DM, Meng W, Deal DD, Busija DW (1994) Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical spreading depression in rabbits. Am J Physiol 266: H1095–H1102

    PubMed  CAS  Google Scholar 

  11. Cutrer FM, Huerter K (2007) Migraine aura. Neurologist 13: 118–125

    Article  PubMed  Google Scholar 

  12. Diener HC, Limmroth V (2005) Migränetherapie. Internist (Berl) 46: 1087–1095

  13. Diener HC, May A (1996) New aspects of migraine pathophysiology: lessons learned from positron emission tomography. Curr Opin Neurol 9: 199–201

    Article  PubMed  CAS  Google Scholar 

  14. Dreier JP, Woitzik J, Fabricius M et al. (2006) Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations. Brain 129: 3224–3237

    Article  PubMed  Google Scholar 

  15. Ebersberger A, Schaible HG, Averbeck B, Richter F (2001) Is there a correlation between spreading depression, neurogenic inflammation, and nociception that might cause migraine headache? Ann Neurol 49: 7–13

    Article  PubMed  CAS  Google Scholar 

  16. Fabricius M, Lauritzen M (1994) Examination of the role of nitric oxide for the hypercapnic rise of cerebral blood flow in rats. Am J Physiol 266: H1457–H1464

    PubMed  CAS  Google Scholar 

  17. Fabricius M, Fuhr S, Bhatia R et al. (2006) Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex. Brain 129: 778–790

    Article  PubMed  Google Scholar 

  18. Gardner-Medwin AR (1981) Possible roles of vertebral neuroglia in potassium dynamics, spreading depression and migraine. J Exp Biol 95: 111–127

    PubMed  CAS  Google Scholar 

  19. Goadsby PJ (2006) Recent advances in the diagnosis and management of migraine. BMJ 332: 25–29

    Article  PubMed  Google Scholar 

  20. Gold L, Back T, Arnold G et al. (1998) Cortical spreading depression-associated hyperemia in rats: involvement of serotonin. Brain Res 783: 188–193

    Article  PubMed  CAS  Google Scholar 

  21. Grafstein B (1956) Mechanism of spreading cortical depression. J Neurophysiol 19: 154–171

    PubMed  CAS  Google Scholar 

  22. Hadjikhani N, Sanchez Del Rio M, Wu O et al. (2001) Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A 98: 4687–4692

    Article  PubMed  CAS  Google Scholar 

  23. Hoffmann J, Reuter U (2007) Aktuelle Therapie der Migräne. Dtsch Med Wochenschr 132: 2153–2158

    Article  PubMed  CAS  Google Scholar 

  24. IHCD (2004) The International Classification of Headache Disorders, 2nd edn. Cephalalgia 24: 1–160

    Google Scholar 

  25. James MF, Smith MI, Bockhorst KH et al. (1999) Cortical spreading depression in the gyrencephalic feline brain studied by magnetic resonance imaging. J Physiol 519: 415–425

    Article  PubMed  CAS  Google Scholar 

  26. Kager H, Wadman WJ, Somjen GG (2000) Simulated seizures and spreading depression in a neuron model incorporating interstitial space and ion concentrations. J Neurophysiol 84: 495–512

    PubMed  CAS  Google Scholar 

  27. Kaube H, Herzog J, Käufer T et al. (2000) Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine. Neurology 55: 139–141

    Article  PubMed  CAS  Google Scholar 

  28. Kirchmann M (2006) Migraine with aura: new understanding from clinical epidemiologic studies. Curr Opin Neurol 19: 286–293

    Article  PubMed  Google Scholar 

  29. Kraig RP, Nicholson C (1978) Extracellular ionic variations during spreading depression. Neuroscience 3: 1045–1059

    Article  PubMed  CAS  Google Scholar 

  30. Lambert GA, Michalicek J, Storer RJ, Zagami AS (1999) Effect of cortical spreading depression on activity of trigeminovascular sensory neurons. Cephalalgia 19: 631–638

    Article  PubMed  CAS  Google Scholar 

  31. Lashley KS (1941) Patterns of cerebral integration indicated by the scotomas of migraine. Arch Neurol Psychiatry 46: 331–339

    Google Scholar 

  32. Lauritzen M, Olsen TS, Lassen NA, Paulson OB (1983) Regulation of regional cerebral blood flow during and between migraine attacks. Ann Neurol 14: 569–572

    Article  PubMed  CAS  Google Scholar 

  33. Lauritzen M (1991) Links between cortical spreading depression and migraine: clinical and experimental aspects. In: Olesen J (ed) Migraine and other headaches. Raven Press, New York, pp 143–151

  34. Lauritzen M (1994) Pathophysiology of the migraine aura. The spreading depression theory. Brain 117: 199–210

    Article  PubMed  Google Scholar 

  35. Leão AAP (1944) Spreading depression of activity in the cerebral cortex. J Neurophysiol 7: 359–390

    Google Scholar 

  36. Leão AAP (1947) Further observations on the spreading depression of activity in the cerebral cortex. J Neurophysiol 10: 409–419

    PubMed  Google Scholar 

  37. Lehmenkühler A, Zidek W, Staschen M, Caspers H (1981) Cortical pH and pCa in relation to DC potential shifts during spreading depression and asphyxiation. In: Sykova E, Hnik P, Vyklicky L (eds) Ion-selective microelectrodes and their use in excitable tissues. Plenum Press, New York, pp 225–229

  38. Lehmenkühler A (1990) Spreading depression-Reaktionen an der Hirnrinde: Störungen des extrazellulären Mikromilieus. Z EEG-EMG Elektroenzephalogr Elektromyogr Verwandte Geb 21: 1–6

  39. Lehmenkühler A, Grotemeyer KH, Tegtmeier F (eds) (1993) Migraine: basic mechanisms and treatment. Urban & Schwarzenberg, München Berlin Wien

  40. Lehmenkühler A, Richter F (1993) Distribution of spreading depression in upper and lower depths of the rat cerebral cortex and its possible implications on the type of human migraine. In: Lehmenkühler A, Grotemeyer KH, Tegtmeier F (eds) (1993) Migraine: basic mechanisms and treatment. Urban & Schwarzenberg, München Berlin Wien, pp 267–278

  41. Marrannes R, Willems R, De Prins E, Wauquier A (1988) Evidence for a role of the N-methyl-D-aspartate (NMDA) receptor in cortical spreading depression in the rat. Brain Res 457: 226–240

    Article  PubMed  CAS  Google Scholar 

  42. Mayevsky A, Doron A, Manor T et al. (1996) Cortical spreading depression recorded from the human brain using a multiparametric monitoring system. Brain Res 740: 268–274

    Article  PubMed  CAS  Google Scholar 

  43. Mazel T, Richter F, Vargova L, Sykova E (2002) Changes in extracellular space volume and geometry induced by cortical spreading depression in immature and adult rats. Physiol Res 51 [suppl 1]: S85–S93

    Google Scholar 

  44. Milner PM (1958) Note on a possible correspondence between the scotomas of migraine and spreading depression of Leão. Electroencephalogr Clin Neurophysiol 10: 705

    Article  PubMed  CAS  Google Scholar 

  45. Moskowitz MA (1990) Basic mechanisms in vascular headache. Neurol Clin 8: 801–815

    PubMed  CAS  Google Scholar 

  46. Read SJ, Hirst WD, Upton N, Parsons AA (2001) Cortical spreading depression produces increased cGMP levels in cortex and brain stem that is inhibited by tonabersat (SB-220453) but not sumatriptan. Brain Res 891: 69–77

    Article  PubMed  CAS  Google Scholar 

  47. Richter F, Ebersberger A, Schaible HG (2002) Blockade of voltage-gated calcium channels in rat inhibits repetitive cortical spreading depression. Neurosci Lett 334: 123–126

    Article  PubMed  CAS  Google Scholar 

  48. Sachs M, Pape HC, Speckmann EJ, Gorji A (2007) The effect of estrogen and progesterone on spreading depression in rat neocortical tissues. Neurobiol Dis 25: 27–34

    Article  PubMed  CAS  Google Scholar 

  49. Somjen GG, Aitken PG, Czeh GL et al. (1992) Mechanism of spreading depression: a review of recent findings and a hypothesis. Can J Physiol Pharmacol 70 [suppl]: S248–S254

    Google Scholar 

  50. Somjen GG (2001) Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. Physiol Rev 81: 1065–1096

    PubMed  CAS  Google Scholar 

  51. Sramka M, Brozek G, Bures J, Nadvornik P (1977–1978) Functional ablation by spreading depression: possible use in human stereotactic neurosurgery. Appl Neurophysiol 40: 48–61

    Article  PubMed  Google Scholar 

  52. Strong AJ, Fabricius M, Boutelle MG et al. (2002) Spreading and synchronous depressions of cortical activity in acutely injured human brain. Stroke 33: 2738–2743

    Article  PubMed  Google Scholar 

  53. Strong AJ, Dardis R (2005) Depolarisation phenomena in traumatic and ischaemic brain injury. Adv Tech Stand Neurosurg 30: 3–49

    Article  PubMed  CAS  Google Scholar 

  54. Strong AJ, Hartings JA, Dreier JP (2007) Cortical spreading depression: an adverse but treatable factor in intensive care? Curr Opin Crit Care 13: 126–133

    Article  PubMed  Google Scholar 

  55. Umegaki M, Sanada Y, Waerzeggers Y et al. (2005) Peri-infarct depolarizations reveal penumbra-like conditions in striatum. J Neurosci 25: 1387–1394

    Article  PubMed  CAS  Google Scholar 

  56. Van Harreveld A (1959) Compounds in brain extracts causing spreading depression of cerebral cortical activity and contraction of crustacean muscle. J Neurochem 3: 300–315

    Article  Google Scholar 

  57. Wahl F, Obrenovitch TP, Hardy AM et al. (1994) Extracellular glutamate during focal cerebral ischaemia in rats: time course and calcium dependency. J Neurochem 63: 1003–1011

    Article  PubMed  CAS  Google Scholar 

  58. Weiller C, May A, Limmroth V et al. (1995) Brain stem activation in spontaneous human migraine attacks. Nat Med 1: 658–660

    Article  PubMed  CAS  Google Scholar 

  59. Wolff HG (1963) Headache and other head pain, 2nd edn. Oxford Univ. Press, New York

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Authors and Affiliations

  1. Institut für Physiologie I/Neurophysiologie, Friedrich-Schiller-Universität Jena, Teichgraben 8, 07740, Jena, Deutschland

    F. Richter

  2. Schmerztherapeutisches Zentrum - Tagesklinik, St.-Vinzenz-Krankenhaus Düsseldorf, Düsseldorf, Deutschland

    A. Lehmenkühler

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  1. F. Richter
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Correspondence to F. Richter.

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Richter, F., Lehmenkühler, A. Cortical spreading depression (CSD). Schmerz 22, 544–550 (2008). https://doi.org/10.1007/s00482-008-0653-9

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Schlüsselwörter

  • Cortical spreading depression
  • Migräne
  • Aura
  • Triptane
  • COSBID

Keywords

  • Cortical spreading depression
  • Migraine
  • Aura
  • Triptans
  • COSBID