The role of the nitric oxide pathway in brain injury and its treatment — From bench to bedside

Garry, Payashi; Ezra, Martyn; Rowland, Matthew; Westbrook, J. L.; Pattinson, Kyle T. S.

doi:10.1016/j.expneurol.2014.10.017

Cited by 319 publications

(267 citation statements)

References 108 publications

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“…[9][10][11] In preclinical studies, NO donors reduced lesion size and increased cerebral blood flow, but only if given early. 12 In multiple pilot randomized controlled trials, NO donors (specifically intravenous sodium nitroprusside and transdermal glyceryl trinitrate [GTN]) reduced BP, pulse pressure, variability, and peak systolic BP; maintained cerebral blood flow (in spite of BP reduction); and improved arterial compliance.…”

mentioning

confidence: 99%

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Woodhouse

Scutt

Krishnan

et al. 2015

Stroke

100

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T reatment options for acute ischemic stroke are limited to thrombolysis, aspirin, hemicraniectomy and stroke unit care, [1][2][3][4] and mechanical thrombectomy. [5][6][7] Although there are no definitive treatments for acute intracerebral hemorrhage, lowering blood pressure (BP) might be beneficial. 8 As a result, new interventions are still needed and, ideally, ones that are simple to administer and relevant irrespective of stroke type so that they can be given prehospital or immediately on admission to hospital before neuroimaging.Nitric oxide (NO) donors are a candidate treatment for acute stroke. [9][10][11] In preclinical studies, NO donors reduced lesion size and increased cerebral blood flow, but only if given early. 12 In multiple pilot randomized controlled trials, NO donors (specifically intravenous sodium nitroprusside and transdermal glyceryl trinitrate [GTN]) reduced BP, pulse pressure, variability, and peak systolic BP; maintained cerebral blood flow (in spite of BP reduction); and improved arterial compliance. [13][14][15][16][17] Although sodium nitroprusside attenuated platelet function, GTN had no effect on platelets, 13,14 suggesting that it could be given to patients whether they had ischemic or hemorrhagic stroke. In a small trial of GTN administered by paramedics before hospital admission (with median time toBackground and Purpose-Nitric oxide donors are candidate treatments for acute stroke, potentially through hemodynamic, reperfusion, and neuroprotectant effects, especially if given early. Although the large Efficacy of Nitric Oxide in Stroke (ENOS) trial of transdermal glyceryl trinitrate (GTN) was neutral, a prespecified subgroup suggested that GTN improved functional outcome if administered early after stroke onset. Methods-Prospective analysis of subgroup of patients randomized into the ENOS trial within 6 hours of stroke onset.Safety and efficacy of GTN versus no GTN were assessed using data on early and late outcomes. Results-Two hundred seventy-three patients were randomized within 6 hours of ictus: mean (SD) age, 69.9 (12.7) years; men, 154 (56.4%); ischemic stroke, 208 (76.2%); Scandinavian Stroke Scale, 32.1 (11.9); and total anterior circulation syndrome, 86 (31.5%). When compared with no GTN, the first dose of GTN lowered blood pressure by 9.4/3.3 mm Hg (P<0.01, P=0.064) and shifted the modified Rankin Scale to a better outcome by day 90, adjusted common odds ratio, 0.51 (95% confidence interval, 0.32-0.80). Significant beneficial effects were also seen with GTN for disability (Barthel Index), quality of life (EuroQol-Visual Analogue Scale), cognition (telephone Mini-Mental State Examination), and mood (Zung Depression Scale admission of 55 minutes), GTN seemed to improve functional outcome, assessed as the modified Rankin Scale (mRS). 17When assessed in a large international trial involving patients with stroke within 48 hours, GTN was safe to administer but did not alter mRS, the primary outcome. 18The potential benefit of GTN when administered early 17 suggested that the...

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mentioning

confidence: 99%

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Woodhouse

Scutt

Krishnan

et al. 2015

Stroke

100

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“…It has been demonstrated that NO constitutes a potent endogenous vasodilator, which directly acts on vascular smooth cells, causing vascular relaxation [72]. In addition, NO also has neuroprotective function [73].…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Drug treatment of cerebral vasospasm after subarachnoid hemorrhage following aneurysms

Liu

Qiu

et al. 2016

Chin Neurosurg Jl

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Cerebral vasospasm (CVS) is a common and severe complication of aneurysmal subarachnoid hemorrhage (aSAH). Despite the improvement in treatment of aSAH, CVS complicating aSAH has remained the main cause of death. CVS begins most often on the third day after the ictal event and reaches the maximum on the 5th-7th postictal days. Several therapeutic modalities have been employed to prevent or reverse CVS. The aim of this review is to summate all the available drug treatment modalities for vasospasm.

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“…In contrast, iNOS is mainly found in the microglia, astrocytes, macrophages and neutrofiles. It is not Ca 2+ -calmoduline -dependent, but its long activity defines the concentration of cytokines, as well as inflammatory and immunological stimulation [16,17]. [4] NO functions as a neurotransmitter in the peripheral and central nervous system (CNS), however, it is not like the typical neurotransmitter stored in the synaptic vesicles, but after its synthesis, it is quickly released to the synaptic cleft.…”

Section: Introductionmentioning

confidence: 99%

Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

Polakowska

Orzelska‐Górka

Talarek

2016

Current Issues in Pharmacy and Medical Sciences

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Nitric oxide (NO) is a relatively novel messenger that plays a significant role in a wide range of physiological processes. Currently, it is known that, both, lack and excess of NO can cause diseases, thus a lot of substances have been discovered and utilized which can change the concentration of this molecule within the organism. The aim of the present work is to provide an overview of currently used agents modulating the L-arginine:NO:cGMP pathway, as well as to summarize current understanding of their pharmacological profiles. Nowadays, most of these agents are employed particularly in the treatment of cardiovascular diseases. Further studies can hold promise for enhancing the therapeutic equipment for a variety of other impairments, such as osteoporosis, and also in treatments of the central nervous system.

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The role of the nitric oxide pathway in brain injury and its treatment — From bench to bedside

Cited by 319 publications

References 108 publications

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Drug treatment of cerebral vasospasm after subarachnoid hemorrhage following aneurysms

Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

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