Nitric oxide and the brain. Part 1: Mechanisms of regulation, transport and effects on the developing brain

AbstractWe evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.

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Adverse Effect of a Presenilin-1 Mutation in Microglia Results in Enhanced Nitric Oxide and Inflammatory Cytokine Responses to Immune Challenge in the Brain

NeuroMolecular Medicine ◽

10.1385/nmm:2:1:29 ◽

2002 ◽

Vol 2 (1) ◽

pp. 29-46 ◽

Cited By ~ 52

Author(s):

Mark P. Mattson ◽

Jaewon Lee ◽

Sic L. Chan

Keyword(s):

Nitric Oxide ◽

Adverse Effect ◽

Inflammatory Cytokine ◽

Presenilin 1 ◽

Immune Challenge ◽

Cytokine Responses ◽

Presenilin 1 Mutation ◽

The Brain

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A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury

The Scientific World JOURNAL ◽

10.1155/2014/432318 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 14

Author(s):

Yong-Peng Yu ◽

Xiang-Lin Chi ◽

Li-Jun Liu

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Hydrogen Sulfide ◽

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Leukocyte Adhesion ◽

Ischemia Reperfusion ◽

The Brain

Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH.

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NO nerves in a tapeworm. NADPH-diaphorase histochemistry in adult Hymenolepis diminuta

Parasitology ◽

10.1017/s0031182000067603 ◽

1996 ◽

Vol 113 (6) ◽

pp. 559-565 ◽

Cited By ~ 27

Author(s):

M. K. S. Gustafsson ◽

A. M. Lindholm ◽

N. B. Terenina ◽

M. Reuter

Keyword(s):

Nitric Oxide ◽

Nervous System ◽

Nadph Diaphorase ◽

Hymenolepis Diminuta ◽

Staining Reaction ◽

Internal Seminal Vesicle ◽

Oxide Synthase ◽

First Time ◽

The Brain ◽

Nerve Cords

SUMMARYThe free radical nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS), has recently been discovered to function as a neuronal messenger. The presence of NOS was detected in the nervous system of adult Hymenolepis diminuta with NADPH-diaphorase (NADPH-d) histochemistry. The NADPH-d histochemical reaction is regarded as a selective marker for NOS in neuronal tissue. NADPH-d staining was observed in nerve fibres in the main and minor nerve cords and the transverse ring commissures, and in cell bodies in the brain commissure, along the main nerve cords, in the suckers and the rostellar sac. NADPH-d staining was also observed in the wall of the internal seminal vesicle and the genital atrium. The pattern of NADPH-d staining was compared with that of the 5-HT immunoreactive nervous elements. The NADPH-d staining reaction and the 5-HT immunoreactivity occur in separate sets of neurons. This is the first time the NADPH-d reaction has been demonstrated in the nervous system of a flatworm, indicating that NOS is present and that NO can be produced at this level of evolution.

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Role of Nitric Oxide in Regulation of Brain Stem Circulation during Hypotension

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199710000-00011 ◽

1997 ◽

Vol 17 (10) ◽

pp. 1089-1096 ◽

Cited By ~ 23

Author(s):

Kazunori Toyoda ◽

Kenichiro Fujii ◽

Setsuro Ibayashi ◽

Tetsuhiko Nagao ◽

Takanari Kitazono ◽

...

Keyword(s):

Nitric Oxide ◽

Brain Stem ◽

Topical Application ◽

Basilar Artery ◽

Group Versus ◽

Control Group ◽

Cranial Window ◽

Severe Hypotension ◽

The Brain

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

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Abstract 814: Atorvastatin Attenuates Oxidative Stress And Improves Neuronal Nitric Oxide Synthase In The Brain Stem Of Heart Failure Mice

Circulation ◽

10.1161/circ.116.suppl_16.ii_157-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Joseph Francis ◽

Li Yu ◽

Anuradha Guggilam ◽

Srinivas Sriramula ◽

Irving H Zucker

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Myocardial Infarction ◽

Heart Failure ◽

Brain Stem ◽

Mrna Expression ◽

Natriuretic Peptide ◽

Left Ventricular ◽

Neuronal Nos ◽

The Brain

3-Hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the incidence of myocardial infarction independent of their lipid-lowering effects. Nitric oxide (NO) in the central nervous system contributes to cardiovascular regulatory mechanisms. Imbalance between nitric oxide (NO) and superoxide anion (O 2 . − ) in the brain may contribute to enhanced sympathetic drive in heart failure (HF). This study was done to determine whether treatment with atorvastatin (ATS) ameliorates the imbalance between NO and O 2 . − production in the brain stem and contributes to improvement of left ventricular (LV) function. Methods and Results: Myocardial infarction (MI) was induced by ligation of the left coronary artery or sham surgery. Subsequently, mice were treated with ATS (10 μg/kg) (MI + ATS), or vehicle (MI + V). After 5 weeks, echocardiography revealed left ventricular dilatation in MI mice. Realtime RT-PCR indicated an increase in the mRNA expression of the LV hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Neuronal NOS (nNOS) and endothelial NOS (eNOS) mRNA expression were significantly reduced, while that of NAD(P)H oxidase subunit (gp91phox) expression was elevated in the brain stem of MI mice. Compared with sham-operated mice, ATS-treated mice showed reduced cardiac dilatation, decreased ANP and BNP in the LV. ATS also reduced gp91phox expression and increased nNOS mRNA expression in the brain stem, while no changes in eNOS and iNOS were observed. Conclusion: These findings suggest that ATS reduces oxidative stress and increases neuronal NOS in the brain stem, and improves left ventricular function in heart failure.

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