Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration

Santos, R. M.; Lourenço, Cátia F.; Ledo, Ana; Barbosa, Rui M.; Laranjinha, João

doi:10.1155/2012/391914

Cited by 44 publications

(39 citation statements)

References 161 publications

(179 reference statements)

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“…139 Mathematical models of NO dynamics illustrate the complexity of this problem. 140 NO is so reactive that questions have been raised about the accuracy of its determination.…”

Section: 5 Nitric Oxidementioning

confidence: 99%

A review of flux considerations for in vivo neurochemical measurements

Paul

Stenken

2015

Analyst

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The mass transport or flux of neurochemicals in the brain and how this flux affects chemical measurements and their interpretation is reviewed. For all endogenous neurochemicals found in the brain, the flux of each of these neurochemicals exists between sources that produce them and the sites that consume them all within μm distances. Principles of convective-diffusion are reviewed with a significant emphasis on the tortuous paths and discrete point sources and sinks. The fundamentals of the primary methods of detection, microelectrodes and microdialysis sampling of brain neurochemicals are included in the review. Special attention is paid to the change in the natural flux of the neurochemicals caused by implantation and consumption at microelectrodes and uptake by microdialysis. The detection of oxygen, nitric oxide, glucose, lactate, and glutamate, and catecholamines by both methods are examined and where possible the two techniques (electrochemical vs. microdialysis) are compared. Non-invasive imaging methods: magnetic resonance, isotopic fluorine MRI, electron paramagnetic resonance, and positron emission tomography are also used for different measurements of the above-mentioned solutes and these are briefly reviewed. Although more sophisticated, the imaging techniques are unable to track neurochemical flux on short time scales, and lack spatial resolution. Where possible, determinations of flux using imaging are compared to the more classical techniques of microdialysis and microelectrodes.

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“…139 Mathematical models of NO dynamics illustrate the complexity of this problem. 140 NO is so reactive that questions have been raised about the accuracy of its determination.…”

Section: 5 Nitric Oxidementioning

confidence: 99%

A review of flux considerations for in vivo neurochemical measurements

Paul

Stenken

2015

Analyst

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“…NO mediates numerous physiologic processes including, among others, vasodilatation, regulation of immune response, neuronal development, neurotransmission, as well as memory and learning [10] . NO also regulates gene transcription and mRNA translation, and produces post-translational modifications of proteins [11] .…”

Section: Academy Of Neurology As Well As the Alzheimer's Associationmentioning

confidence: 99%

New Insights into Possible Role of NOS-NO-ADMA Pathway Dysfunction in the Development of Cognitive Decline and Dementia: Exploring the Vascular Features of Alzheimer’s Disease

Začiragić¹

2015

International Journal of Neurology Research

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In recent years significant overlap between cardio-metabolic risk factors and cognitive decline has been reported. Cardio-metabolic and vascular factors shown to be associated with Alzheimer's disease (AD) and other forms of dementia include midlife diabetes and hypertension, cerebrovascular lesions, diminished vascular function, dyslipidemia, obesity, and cigarette smoking. Accordingly, it has been recently proposed that amyloid is not the cause of AD but merely a marker and a later consequence of upstream changes that lead to neuronal and synaptic losses. However, although the idea that features of vascular dysfunction and injury are present in cognitive decline and AD patients was suggested over 25 years ago, the role of cardio-metabolic and cerebrovascular mechanisms in the pathogenesis of AD is far from being fully elucidated. Based on newly proposed vascular hypothesis, there is an impaired structure and function of cerebral blood vessels and cells in patients with cognitive decline and AD which is mediated by vascular oxidative stress. Consistent with these observations, the importance of endothelial dysfunction in the development of AD has been highlighted. One of the most prominent features of endothelial dysfunction is decreased production and bioavailability of Nitric Oxide (NO). Based on versatile properties in physiological as well as in pathophysiological conditions NO is regarded as a key molecule for longevity and cardiovascular health. NO is produced by three different isoforms of the enzyme NO synthase (NOS), namely: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). Reduced NO bioavailability and altered vascular expression and activity of NOS enzymes are implicated as major molecular players in the process of vascular aging. In the process of aging, the mechanisms by which NOS enzymes promote vascular dysfunction are specific for each NOS isoform. Normal activity of eNOS is required for the balanced production/bioavailability of NO, which is the main prerequisite for optimal vascular function. Conversely, excessive amount of NO produced by iNOS contributes to vascular dysfunction. Furthermore, although the possible role of nNOSderived NO in aging-associated vascular dysfunction is far from being fully elucidated, experimental findings indicate that impaired perivascular NO release from nNOS increases vasoconstriction in aged arterioles. Oxidative stress and inhibitors of NO synthase are regarded as most potent initiators of disturbed production and bioavailability of NO. Important endogenous inhibitor of all three isoforms of NOS is asymmetrical dimethylarginine (ADMA). It has been recently proposed that ADMA may be a possible link between vascular disease and dementia. Based on this assumption ADMA might represent a unifying pathophysiological pathway linking the presence of vascular risk factors with the onset and progression of cognitive decline and dementia. These observations were made based on good evidence from literature that higher plasma ADMA concentrations favor ath...

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“…For the coculture experiment, BV-2 mouse microglia cells were seeded in triplicate at the density of 2×10 5 cells/well in 6-well plates.…”

Section: Microglia-conditioned Media Systemmentioning

confidence: 99%

“…3,4) These pro-inflammatory mediators and cytokines may regulate neuronal survival and are subsequently involved in the processes of neurodegeneration. [5][6][7][8] Therefore, inhibition of microglia activation may be an effective approach for the treatment of neurodegenerative diseases.…”

mentioning

confidence: 99%