AVBS location:Brisbane, Queensland, Australia date:7-11 September 2006
Traumatic brain injury causes a biphasic response in nitric oxide (NO) levels: an initial increase rapidly followed by a drop below baseline values for at least 3 hours. We investigated to which NO synthase (NOS) isoform the decrease in NO concentration is related by in vivo administration of NOS inhibitors after neurotrauma in rats. Near infrared spectroscopy was used to study cerebral hemodynamics.
Vasoconstriction in sham animals induced by the neuronal NOS inhibitor 7NI (total cerebral hemoglobin (HbT): 95.8±7.6 to 84.9±9.1, p=0.004; venous oxygen saturation (SvO2): 78.4±3.3 to 71.2±5.1, p=0.011) was totally abolished by neurotrauma, while l-NAME (endothelial NOS and neuronal NOS inhibition) resulted in the expected vasoconstriction in both sham (HbT: 92.4±14.4 to 75.9±15.3, p<0.001; SvO2: 76.6±4.7 to 64.9±3.7, p<0.001) and neurotrauma animals (HbT: 91.1±16.3 to 85.5±16.3, p=0.032; SvO2: 65.6±3.2 to 57.1±8.3, p=0.045). Also, inhibition of neuronal NOS is known to induce an uncoupling of cerebral blood flow and metabolism, which clearly occurs after induction of neurotrauma compared to sham animals (cerebral metabolic rate of oxygen index: 42.0±13.9 to 44.8±16.4, p=0.268; cerebral blood flow index: 13.5±3.0 to 9.2±3.4, p<0.001; arterio-venous oxygen difference: 3.17±1.01 to 5.20±1.77, p<0.001).
We conclude that neuronal NOS activity is largely diminished and may be the major contributor to the NO decrease early after traumatic brain injury, while endothelial NOS remains unaltered.