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Therapeutisch induzierte Arteriogenese im Gehirn

Ein neuer Ansatz zur Prävention der zerebralen Ischämie bei stenosierenden Gefäßerkrankungen

Therapeutically induced arteriogenesis in the brain

A new approach for treating cerebral hypoperfusion following extracranial artery stenosis

Der Nervenarzt volume 77, pages 215–220 (2006)Cite this article

Zusammenfassung

Der Schlaganfall ist in den westlichen Industrieländern die dritthäufigste Todesursache und die häufigste Ursache einer bleibenden Pflegebedürftigkeit. Er beruht auf einer zerebralen Minderperfusion, meist in Folge intra- oder extrakranieller Gefäßverschlüsse, und wird in seiner Schwere von der individuellen Ausprägung der verfügbaren Kollateralgefäße beeinflusst. Im Herzen und in der peripheren Zirkulation konnte experimentell wie klinisch nachgewiesen werden, dass arterielle Minderperfusionen durch die therapeutische Induktion der Arteriogenese — dem adaptativen Wachstum der Kollateralarterien — gemindert oder verhindert werden kann. Um diesen Therapieansatz für das ZNS nachzuweisen, wurde der Einfluss und Verlauf der zerebralen Arteriogenese während chronischer Minderdurchblutung des Gehirns untersucht. Die medikamentöse Stimulation der Kollateralgefäßbildung mit dem Wachstumsfaktor GM-CSF (Granulozyten-Makrophagen-Kolonie-stimulierender Faktor) führte hierbei zu einer signifikanten Zunahme des Durchmessers von intrakraniellen Arterien, einer signifikanten Verbesserung der zerebralen hämodynamischen Reserve und einer signifikanten Reduktion des Energiedefizits nach hämodynamisch induziertem Schlaganfall. Die therapeutisch induzierte Arteriogenese ist ein viel versprechender neuer Ansatz zur Prophylaxe zerebraler Ischämien bei Patienten mit stenosierenden Gefäßerkrankungen.

Summary

Stroke is the leading cause of disability and a major cause of death in Germany and the western world. Ischemic stroke involves different pathophysiologic mechanisms such as thromboembolic vascular occlusion, cerebral micro- or macroangiopathy, extracranial arterial stenosis, and cardiac embolism. Experimental and clinical studies have shown that arteriogenesis, the adaptive growth of pre-existing collateral arteries, can be therapeutically enhanced in peripheral circulation and the heart. We examined the consequences to time course and hemodynamics of brain arteriogenesis in a chronic hypoperfusion model following systemic administration of the hemopoietic growth factor called granulocyte macrophage colony stimulating factor (GM-CSF). Treatment with GM-CSF led to the growth of intracranial collateral arteries, which improved the cerebral hemodynamic reserve and significantly reduced energy failure when brains were additionally challenged by hypotension. Therapeutically induced arteriogenesis may be of considerable interest for preventing infarction in patients with uncompensated cerebrovascular disease.

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Affiliations

  1. Abteilung Kardiologie und Angiologie, Innere Medizin III, Forschergruppe für experimentelle und klinische Arteriogenese, Universitätsklinikum Freiburg

    H.-J. Busch, I. Buschmann, E. Schneeloch & C. Bode

  2. Medizinische Klinik — Kardiologie/Center for Cardiovascular Research, Forschergruppe für experimentelle und klinische Arteriogenese, Charité Berlin

    I. Buschmann

  3. Abteilung für experimentelle Neurologie, Max-Planck-Institut für neurologische Forschung, Köln

    H.-J. Busch, E. Schneeloch, G. Mies & K.-A. Hossmann

  4. Abteilung Kardiologie und Angiologie, Innere Medizin III, Hugstetterstraße 55, 79106, Freiburg, Deutschland

    H.-J. Busch

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  1. H.-J. Busch
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  2. I. Buschmann
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  3. E. Schneeloch
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  4. C. Bode
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  5. G. Mies
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  6. K.-A. Hossmann
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Correspondence to H.-J. Busch.

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Busch, HJ., Buschmann, I., Schneeloch, E. et al. Therapeutisch induzierte Arteriogenese im Gehirn. Nervenarzt 77, 215–220 (2006). https://doi.org/10.1007/s00115-005-1988-4

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  • DOI: https://doi.org/10.1007/s00115-005-1988-4

Schlüsselwörter

  • Arteriogenese
  • Schlaganfall
  • GM-CSF
  • Drei-Gefäß-Okklusion
  • 3-VO

Keywords

  • Arteriogenesis
  • Stroke
  • Granulocyte macrophage colony stimulating factor
  • Three-vessel occlusion
  • 3-VO