Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute stroke

Bath, Philip M; Krishnan, Kailash; Appleton, Jason P.

doi:10.1002/14651858.cd000398.pub2

Cited by 41 publications

(22 citation statements)

References 79 publications

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“…PG is the main mediator of inflammation that includes edema and vascular permeability increase. Therefore, NOS inhibitors prevent the inflammatory reactions and have anti-inflammatory effects depending on their dose and the administration route [34]. In future studies, the effects of NOS inhibitors should be considered in order to evaluate the applied medical and surgical interventions on NP patients and to completely understand the NP pathogenesis and if they have a possible role in prevention of the recurrence.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Inducible Nitric Oxide Synthase in Allergic and Nonallergic Nasal Polyp

Sadek

Abdelwahab

Eid

et al. 2019

Oxidative Medicine and Cellular Longevity

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Sinonasal polyps are very common benign lesions of the nasal mucosa. Most of nasal polyps (NP) are idiopathic, and the pathophysiology of this disease is still incompletely understood. Nitric oxide (NO) is a reactive molecule generated by nitric oxide synthase (NOS). NO has been identified as an important mediator in airway function and pathogenesis of several respiratory system diseases. Histological and genetical expression of iNOS was detected to evaluate the role of NO in the pathogenesis of allergic (ANP) and nonallergic nasal polyps (NANP). Forty patients with nasal polyps (20 allergic and 20 nonallergic) were identified by history, clinical examination, and investigation. NPs were obtained from the middle turbinate (MT) during concha bullosa surgery. Twenty normal MT nasal tissues were taken as the control from patients undergoing concha bullosa surgery, without any evidence of allergy or inflammation. A nasal polyp specimen from each patient was subjected for immune-histochemical study followed by histological examination to detect the expression of iNOS. RT-PCR was used to evaluate the iNOS gene expression in isolated tissues. The expression of iNOS in both epithelial and stromal layers was greater in NP than in MT tissues. The ANP group showed more iNOS expression than those of the NANP group. The relative mRNA levels of iNOS gene were significantly higher in ANP (2.5-fold) compared to the normal (1.02-fold, P < 0.001) and NANP (1.5-fold, P < 0.01) groups. NP exhibited a significantly high expression of iNOS at both histological and genetical levels. NO might be an essential factor in the life history of NP. Further studies in a larger sample size are required to explain the probable mechanisms of NO in pathogenesis of NP.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Inducible Nitric Oxide Synthase in Allergic and Nonallergic Nasal Polyp

Sadek

Abdelwahab

Eid

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Recently, a systematic review has investigated safety and efficacy of the NO donor transdermal glyceryl trinitrate when applied after stroke. Patients showed blood pressure lowering, but outcome was not ameliorated [ 30 ]. Of note, the analyzed studies included both ischemic and hemorrhagic stroke patients.…”

Section: Discussionmentioning

confidence: 99%

Dimethylarginines in patients with intracerebral hemorrhage: association with outcome, hematoma enlargement, and edema

Worthmann

Martens‐Lobenhoffer

et al. 2017

J Neuroinflammation

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BackgroundAsymmetric dimethylarginine (ADMA)––the most potent endogenous NO-synthase inhibitor, has been regarded as mediator of endothelial dysfunction and oxidative stress. Considering experimental data, levels of ADMA and its structural isomer symmetric dimethylarginine (SDMA) might be elevated after intracerebral hemorrhage (ICH) and associated with clinical outcome and secondary brain injury.MethodsBlood samples from 20 patients with acute ICH were taken at ≤ 24 h and 3 and 7 days after the event. Nine patients had favorable (modified Rankin Scale (mRS) at 90 days 0–2) outcome, and 11 patients unfavorable outcome (mRS 3–6). Patients’ serum ADMA, SDMA, and L-arginine levels were determined by high-performance liquid chromatography–tandem mass spectrometry. Levels were compared to those of 30 control subjects without ICH. For further analysis, patients were grouped according to outcome, hematoma and perihematomal edema volumes, occurrence of hematoma enlargement, and cytotoxic edema as measured by computed tomography and serial magnetic resonance imaging.ResultsLevels of ADMA––but not SDMA and L-arginine––were elevated in ICH patients compared to controls (binary logistic regression analysis: ADMA ≤ 24 h, p = 0.003; 3 days p = 0.005; 7 days p = 0.004). If patients were grouped according to outcome, dimethylarginines were increased in patients with unfavorable outcome. The binary logistic regression analysis confirmed an association of SDMA levels ≤ 24 h (p = 0.048) and at 3 days (p = 0.028) with unfavorable outcome. ADMA ≤ 24 h was increased in patients with hematoma enlargement (p = 0.003), while SDMA ≤ 24 h was increased in patients with large hematoma (p = 0.029) and perihematomal edema volume (p = 0.023).ConclusionsOur data demonstrate an association between dimethylarginines and outcome of ICH. However, further studies are needed to confirm this relationship and elucidate the mechanisms behind.

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“…To date, only glyceryl trinitrate (GTN), an NO donor commonly used in the management of angina, has progressed to clinical trials. A recent systematic review, however, highlighted that despite reductions in blood pressure, there is insufficient evidence to recommend GTN in AIS (Bath et al, 2017). Further pre-clinical evidence is required before other NO-based candidate therapies can progress to the clinical stage.…”

Section: Therapeutic Strategies Targeting Inflammatory Mediatorsmentioning

confidence: 99%

Immunomodulatory Therapeutic Strategies in Stroke

et al. 2019

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The role of immunity in all stages of stroke is increasingly being recognized, from the pathogenesis of risk factors to tissue repair, leading to the investigation of a range of immunomodulatory therapies. In the acute phase of stroke, proposed therapies include drugs targeting pro-inflammatory cytokines, matrix metalloproteinases, and leukocyte infiltration, with a key objective to reduce initial brain cell toxicity. Systemically, the early stages of stroke are also characterized by stroke-induced immunosuppression, where downregulation of host defences predisposes patients to infection. Therefore, strategies to modulate innate immunity post-stroke have garnered greater attention. A complementary objective is to reduce longer-term sequelae by focusing on adaptive immunity. Following stroke onset, the integrity of the blood–brain barrier is compromised, exposing central nervous system (CNS) antigens to systemic adaptive immune recognition, potentially inducing autoimmunity. Some pre-clinical efforts have been made to tolerize the immune system to CNS antigens pre-stroke. Separately, immune cell populations that exhibit a regulatory phenotype (T- and B- regulatory cells) have been shown to ameliorate post-stroke inflammation and contribute to tissue repair. Cell-based therapies, established in oncology and transplantation, could become a strategy to treat the acute and chronic stages of stroke. Furthermore, a role for the gut microbiota in ischaemic injury has received attention. Finally, the immune system may play a role in remote ischaemic preconditioning-mediated neuroprotection against stroke. The development of stroke therapies involving organs distant to the infarct site, therefore, should not be overlooked. This review will discuss the immune mechanisms of various therapeutic strategies, surveying published data and discussing more theoretical mechanisms of action that have yet to be exploited.

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Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute stroke

Cited by 41 publications

References 79 publications

Overexpression of Inducible Nitric Oxide Synthase in Allergic and Nonallergic Nasal Polyp

Overexpression of Inducible Nitric Oxide Synthase in Allergic and Nonallergic Nasal Polyp

Dimethylarginines in patients with intracerebral hemorrhage: association with outcome, hematoma enlargement, and edema

Immunomodulatory Therapeutic Strategies in Stroke

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