gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

Inhaled nitric oxide reduces secondary brain damage after experimental traumatic brain injury

Meeting Abstract

  • Nicole A. Terpolilli - Klinik und Poliklinik für Neurochirurgie, Klinikum der Universität München, München, Germany; Walter-Brendel-Zentrum für Experimentelle Medizin, Klinikum der Universität München, München, Germany
  • Seong-Woong Kim - Walter-Brendel-Zentrum für Experimentelle Medizin, Klinikum der Universität München, München, Germany
  • Serge C. Thal - Walter-Brendel-Zentrum für Experimentelle Medizin, Klinikum der Universität München, München, Germany
  • Wolfgang M. Kuebler - The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's, Toronto, Canada
  • Nikolaus Plesnila - Institut für Schlaganfalls- und Demenzforschung, Klinikum der Universität München, München, Germany

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocMI.14.09

doi: 10.3205/13dgnc403, urn:nbn:de:0183-13dgnc4039

Published: May 21, 2013

© 2013 Terpolilli et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Ischemia, especially pericontusional ischemia, is one of the leading causes of secondary brain damage after traumatic brain injury (TBI). So far efforts to improve cerebral blood flow after TBI were not successful. We previously demonstrated that nitric oxide (NO) applied by inhalation after ischemic stroke improves cerebral perfusion in hypoxic brain regions thus reducing neuronal damage. As regional ischemia in the traumatic penumbra is a key mechanism determining secondary posttraumatic brain damage the aim of the current study was to evaluate the effect of NO inhalation (iNO) after experimental TBI.

Method: In a first set of experiments we studied possible side effects of iNO; tail bleeding time, systemic mean arterial blood pressure (MAP), oxidative damage, intracranial pressure (ICP, intraparenchymal probe), NO – synthase expression and cerebral autoregulation were determined in healthy male C57 bl/6 mice with and without inhalation of 50 ppm iNO (n=8–10 each group). In the second part of the study we studied iNO effects in the early (0–90 minutes after trauma, n=8 each) and longer term (24h–7d, n=8 each) posttraumatic phase in mice that were subjected to Controlled Cortical Impact (CCI) trauma. iNO was started at different time points after trauma in order to determine a therapeutic window. ICP, cerebral perfusion, brain edema formation, blood brain barrier disruption, lesion volume, and neurological outcome were recorded.

Results: NO inhalation significantly improved cerebral blood flow and reduced intracranial pressure after TBI in male C57 Bl/6 mice. iNO application over a 24 h period results in reduced lesion volume, reduced brain edema formation and less blood brain barrier disruption as well as improved neurological function for up to 7 days. No adverse effects, e.g. on cerebral auto-regulation, systemic blood pressure, primary homeostasis, endogenous NOS – expression, or oxidative damage were observed.

Conclusions: The current experimental study demonstrates that NO inhalation effectively reduces brain damage and improves neurological function following TBI. We hypothesize that the underlying protective mechanism consists in a selective dilation of resistance vessels with subsequent increase of cerebral blood flow in the traumatic penumbra, as already demonstrated for cerebral ischemia. NO inhalation is clinically approved for human use and may therefore represent a promising and safe novel treatment strategy for TBI.