Acute Decrease in Cerebral Nitric Oxide Levels after Subarachnoid Hemorrhage

Abstract

Summary: Disturbances in the nitric oxide (NO) vasodilatory pathway have been implicated in acute vasoconstriction and ischemia after subarachnoid hemorrhage (SAH). The authors hypothesize that blood released during SAH leads to vasocon striction by scavenging NO and limiting its availability. This was tested by measuring the major NO metabolites nitrite and nitrate in five different brain regions before and after experi mental SAH. The basal NO metabolites levels were as follows (mean ± SO, f.Lmol/mg wet weight): brain stem, 0.14 ± 0.07; cerebellum, 0.12 ± 0.08; ventral convexity cortex, 0.22 ± 0.15; dorsal convexity cortex, 0.16 ± 0.11; and hippocampus, 0.26 ± 0.17. In sham-operated animals, no effect of the nitric oxide synthase (NOS) inhibitor L G -nitro-L-arginine-methyl-ester (30 mg/kg) was found on NO metabolites 40 minutes after admin istration, but a significant decrease was seen after 120 minutes.Cerebral blood flow decreases acutely and ischemic injury occurs after subarachnoid hemorrhage (SAH) in both experimental and clinical studies. Cerebral arteries have been shown to respond to SAH with a biphasic constriction. An acute constriction begins minutes after the bleed, and delayed vasospasm begins 48 hours later . Although the significance of de layed vasospasm is recognized (Sobey and Faraci, 1998 604The NO metabolites decreased significantly 10 minutes after SAH in all brain regions except for hippocampus, and recov ered to control levels in cerebellum at 60 minutes and in brain stem and dorsal cerebral cortex 180 minutes after SAH, while remaining low in ventral convexity cortex. Nitrite recovered completely in all brain regions at 180 minutes after SAH, whereas nitrate remained decreased in brain stem and ventral convexity cortex. Our results indicate that SAH causes acute decreases in cerebral NO levels by a mechanism other than NOS inhibition and provide further support for the hypothesis that alterations in the NO vasodilatory pathway contribute di rectly to the ischemic insult after SAH.

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

“…In the brain, this tonic level of NO includes the release of NO due to neuronal activity, some of which also affects the vascular tone. SAH was recently shown to affect the short-term levels of NO in the rat brain as measured by assaying the metabolites nitrite and nitrate (121). Between 10 and 120 or 180 min after SAH, there were significantly decreased levels of these metabolites in the 5 regions studied, although recovery towards baseline levels had commenced by 180 min.…”

Role of HCN Channels in Neuronal Hyperexcitability after Subarachnoid Hemorrhage in Rats

“…This time course of HCN1 channel changing is earlier than that of cerebral vasospasm occurring, and closely followed by the time when cortical spreading depolarization begin to appear (Dreier et al, 2006). Additionally, it is generally accepted that the scavenging effect of Hb on NO signaling contributes to a series of pathological changes after SAH (Sehba et al, 2000;Koźniewska et al, 2006;Pluta et al, 2009) and the level of NO determines the neural susceptibility for cortical spreading depolarization after SAH (Petzold et al, 2008). In the current study, the scavenging effect of Hb on NO was observed.…”

Cognitive Evolution of a Patient Who Suffered a Subarachnoid Haemorrhage Eight Years Ago, after Being Treated with Growth Hormone, Melatonin and Neurorehabilitation

“…Following this vasoconstriction, a delayed vasospasm appears, usually more than 48 h after that, as pioneering studies in rats revealed [29,30]. Many theories have tried to explain how this delayed vasospasm occurs, among them an alteration in the production of nitric oxide (NO) by the vascular endothelium [31], hence impairing the vasodilatory activity of this gas and the hemodynamic cerebral autoregulation. Following haemorrhage haemoglobin binds to NO, therefore decreasing its availability [32].…”