gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Long-term effect of VAS203, a novel NO synthase inhibitor, after experimental traumatic brain injury in mice

Langzeit-Effekt von VAS203, einem neuen NO-Synthase Inhibitor, nach experimentellem Schädel-Hirn-Trauma bei der Maus

Meeting Abstract

  • corresponding author A. Ardeshiri - Neurochirurgische Klinik, Klinikum der Universität München - Großhadern
  • A. Ardeshiri - Neurochirurgische Klinik, Klinikum der Universität München - Großhadern
  • N. Terpollili - Institut für Chirurgische Forschung, Klinikum der Universität München - Großhadern
  • K. Zweckberger - Institut für Chirurgische Forschung, Klinikum der Universität München - Großhadern
  • F. Tegtmeier - Vasopharm Biotech, Würzburg
  • N. Plesnila - Neurochirurgische Klinik, Klinikum der Universität München - Großhadern

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocFR.03.01

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2007/07dgnc075.shtml

Published: April 11, 2007

© 2007 Ardeshiri et al.
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Outline

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Objective: Antipterins, a novel class of NO-Synthase (NOS) inhibitors, reduce acute (<24h) post-traumatic ICP increase after experimental traumatic brain injury (TBI). The aim of the current study was to investigate whether the acute effect of antipterins translates into a long-term improvement of neurological function and a reduction of morphological brain damage after TBI in mice.

Methods: C57/Bl6 mice were subjected to controlled cortical impact (CCI). One hour after CCI, animals received 40 mg/kg VAS203 i.v. followed by a continuous infusion of 53 mg/kg/h for the following 3 h (n=10). Control animals (n=10) received the same volume of PBS. On days 1-7 after TBI the body weight and the neurological function of the animals (beam walking and neurological severity score, NSS) were assessed. Contusion volume was determined on histological sections on day 7 after TBI.

Results: Animals receiving VAS203 from 1 to 4 h after TBI lost significantly less weight from day 1-5 after TBI (p<0.01), performed better in the beam walking test (p<0.001), and scored better in the NSS test 1-7 days after TBI (p<0.01) as compared to controls. Secondary contusion expansion of treated animals was significantly reduced by almost 50% on day 7 after trauma (p<0.01).

Conclusions: Inhibition of NO synthases by VAS203 reduces morphological brain damage and improves neurological function following TBI in mice. Antipterins such as VAS203 may therefore represent a novel class of drugs which should be evaluated for the treatment of TBI.