Article
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
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Published: | April 11, 2007 |
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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.