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Die Bedeutung der posttraumatischen Entzündungsreaktion im verletzten Gehirn

The relevance of the inflammatory response in the injured brain

Der Orthopäde volume 36, pages 248–258 (2007)Cite this article

Zusammenfassung

Das Schädel-Hirn-Trauma (SHT) wurde in den letzten Jahren als ein vorwiegend immunologisches und entzündliches Krankheitsbild neu definiert. Diese Erkenntnis basiert auf der Einsicht, dass die überschießende Entzündungsreaktion im verletzten Gehirn zur Ausbildung des posttraumatischen Hirnödems führt und sich dadurch maßgeblich limitierend auf die Prognose der SHT-Patienten auswirkt. Während die Vermittler der Neuroinflammation (z. B. die Zytokin-Kaskade oder das Komplementsystem) durch Studien am Tiermodell weitgehend charakterisiert sind, bleiben deren Interaktionen und pathophysiologische Implikationen im verletzten Gehirn noch unzureichend geklärt. Das mangelnde Verständnis beruht u. a. auf der „dualen Funktion“ der neuroinflammatorischen Reaktion nach SHT. Diese zweischneidige Rolle impliziert, dass spezifische Entzündungsmediatoren je nach lokaler Konzentration, Zeitpunkt und Ort ihrer Expression im Gehirn unterschiedliche Funktionen vermitteln können, von einer gewünschten Neuroprotektion bis hin zur detrimentalen Neurotoxizität.

Der ausbleibende Erfolg antiinflammatorischer Therapieansätze bei SHT-Patienten verdeutlicht die dringende Notwendigkeit der Intensivierung der Grundlagenforschung auf dem Gebiet der posttraumatischen intrazerebralen Entzündungsreaktion. Die vorliegende Arbeit soll die aktuellsten Ergebnisse der experimentellen Forschung auf diesem speziellen Gebiet zusammenfassen und potentielle zukünftige Forschungsrichtungen erörtern.

Abstract

Research efforts in recent years have defined traumatic brain injury (TBI) as a predominantly immunological and inflammatory disorder. This perception is based on the fact that the overwhelming neuroinflammatory response in the injured brain contributes to the development of posttraumatic edema and to neuropathological sequelae which are, in large part, responsible for the adverse outcome. While the “key” mediators of neuroinflammation, such as the cytokine cascade and the complement system, have been clearly defined by studies in experimental TBI models, their exact pathways of interaction and pathophysiological implications remain to be further elucidated. This lack of knowledge is partially due to the concept of a “dual role” of the neuroinflammatory response after TBI. This notion implies that specific inflammatory molecules may mediate diverse functions depending on their local concentration and kinetics of expression in the injured brain. The inflammation-induced effects range from beneficial aspects of neuroprotection to detrimental neurotoxicity.

The lack of success in pushing anti-inflammatory therapeutic concepts from“bench to bedside” for patients with severe TBI strengthens the further need for advances in basic research on the molecular aspects of the neuroinflammatory network in the injured brain. The present review summarizes the current knowledge from experimental studies in this field of research and discusses potential future targets of investigation.

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Danksagung

Die Autoren danken Frau Claudia Conrad für ihre exzellente technisch-experimentelle Arbeit im Forschungslabor. Unsere Forschungsprojekte am SHT-Modell wurden durch Sachbeihilfen der Deutschen Forschungsgemeinschaft (DFG) No. STA635/1-1, STA635/1-2, STA635/2-1 und STA635/2-2 unterstützt.

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Affiliations

  1. Zentrum für Traumatologie, Fachbereich Unfall- und Wiederherstellungschirurgie, Klinikum Sankt Georg, Leipzig, Deutschland

    O.I. Schmidt

  2. Klinik für Unfall- und Wiederherstellungschirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland

    O.I. Schmidt, I. Leinhase & P.F. Stahel

  3. Department of Orthopaedic Surgery,Denver Health Medical Center, University of Colorado School of Medicine, 777 Bannock Street, CO 80204, Denver, USA

    E. Hasenboehler, S.J. Morgan & P.F. Stahel

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  1. O.I. Schmidt
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  2. I. Leinhase
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  3. E. Hasenboehler
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  4. S.J. Morgan
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  5. P.F. Stahel
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Correspondence to P.F. Stahel.

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Schmidt, O., Leinhase, I., Hasenboehler, E. et al. Die Bedeutung der posttraumatischen Entzündungsreaktion im verletzten Gehirn. Orthopäde 36, 248–258 (2007). https://doi.org/10.1007/s00132-007-1061-z

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  • DOI: https://doi.org/10.1007/s00132-007-1061-z

Schlüsselwörter

  • Schädel-Hirn-Trauma
  • Hirnödem
  • Neuroinflammation
  • Forschung
  • Tiermodell

Keywords

  • Brain injury
  • Cerebral edema
  • Neuroinflammation
  • Basic research
  • Experimental model