Neuronal nitric oxide synthase inhibitor has a neuroprotective effect in a rat model of brain injury

Article type: Research Article

Authors: Görlach, Christoph | Hortobágyi, Tibor | Hortobágyi, Szabolcs | Benyó, Zoltán

Affiliations: Department of Physiology, Ludwig-Maximilians University Munich, Germany | Clinical Research Department - 2nd Institute of Physiology, Semmelweis University, Budapest, Hungary

Note: [] Corresponding author: Dr. Christoph Görlach, Physiologisches Institut, Uni-versität München, Pettenkoferstraße 12, D-80336 München, Germany. Tel.: +49 89 599 6521; Fax: +49 89 599 6532; E-mail: [email protected]

Abstract: Purpose: The aim of the present study was to assess the effects of neuronal nitric oxide synthase (NOS I) inhibitors and a combination of NOS I and NOS II inhibitors on lesion volume after experimental brain injury. Methods: Cold lesion of the brain was induced by application of a precooled (.... 78 °C) copper cylinder to the intact dura of the rat for 6 s. Brains were removed 24 h after the injury and lesion volume determined using the triphenyltetrazolium-chloride method. Results: The specific NOS I inhibitor 3-bromo-7-nitroindazole (Br-7-NI) reduced lesion volume significantly by 21 % compared with the vehicle control. In contrast, 7-nitroindazole had no effect on lesion volume. When aminoguanidine, a specific NOS II inhibitor, was adminis-tered after Br-7-NI, lesion volume was significantly reduced but not significantly more than with either compound alone. Conclusion: Brain injury after cold lesion is partly mediated by NOS I activity and can be attenuated successfully with Br-7-NI, while coin-hibition of NOS II does not improve the outcome significantly.

Keywords: Nitric oxide synthase, NOS I, NOS II, 3-bromo-7-nitroindazole, 7-nitroindazole, aminoguanidine, cold brain injury, rat

Journal: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 71-76, 2000