Acute Molecular Perturbation of Inducible Nitric Oxide Synthase with an Antisense Approach Enhances Neuronal Preservation and Functional Recovery after Contusive Spinal Cord Injury

Maggio, Dominic; Chatzipanteli, Katina; Masters, Neil; Patel, Samik; Dietrich, W. Dalton; Pearse, Damien D.

doi:10.1089/neu.2012.2371

Cited by 21 publications

(19 citation statements)

References 45 publications

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“…In addition, nNOS seems to be responsible for DNA damage in a mouse model of PD (Hoang et al, 2009). Markedly increased NO levels can stimulate nitration of many proteins, which tend to aggregate, as reported in the neuronal tissues of patients with neurodegenerative diseases including AD, PD, HD and amyotrophic lateral sclerosis (ALS) (Brown, 2010; Butterfield et al, 2007, 2014; Chung and David, 2010; Dexter and Jenner, 2013; Maggio et al, 2012; Malinski, 2007; Schildknecht et al, 2013). …”

Section: Consequences Of Increased Nitroxidative Stressmentioning

confidence: 94%

“…and NO can be produced, resulting in nitroxidative stress in the brain. Co-existence of NO and superoxide anion can generate more cytotoxic agents, peroxynitrite (ONOO-) and peroxynitrous acid (ONOOH), both of which have been implicated in neuronal cell death (Brown, 2010; Chung and David, 2010; Franco et al, 2013; Gould et al, 2013; Maggio et al, 2012; Malinski, 2007; Schildknecht et al, 2013). Since the brain contains relatively low amounts of glutathione (GSH) and other energy substrates compared to other peripheral tissues, including the liver (Aoyama and Nakaki, 2013; Wali et al, 2011), it is relatively sensitive to severe nitroxidative damage.…”

Section: Consequences Of Increased Nitroxidative Stressmentioning

confidence: 99%

“…For instance, large amounts of NO seems to be important in causing ischemic brain injury (Garcia-Bonilla et al, 2014) and many other neuronal diseases (Butterfield et al, 2007, 2014). Direct evidence for the involvement of iNOS in neuronal diseases was provided by the experimental results of using iNOS -knockout mice, a specific inhibitor of iNOS 1400W (Kumar et al, 2014), or an anti-sense oligonucleotide specific to iNOS (Maggio et al, 2012). For instance, iNOS -knockout mice were resistant to behavioral and synaptic deficits or cerebral plaque formation and premature mortality in animal models of AD (Medeiros et al, 2007; Nathan et al, 2005).…”

Section: Consequences Of Increased Nitroxidative Stressmentioning

confidence: 99%

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Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

et al. 2016

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Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities.

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Section: Consequences Of Increased Nitroxidative Stressmentioning

confidence: 94%

Section: Consequences Of Increased Nitroxidative Stressmentioning

confidence: 99%

Section: Consequences Of Increased Nitroxidative Stressmentioning

confidence: 99%

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Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

et al. 2016

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“…Likewise, topical application of TNF-α antiserum for 10 min after SCI followed by NOS antiserum for 20 min significantly improved functional recovery and BSCB integrity, inhibited edema formation, and diminished spinal cord pathology, suggesting that early blockade of both TNF-α and nNOS is beneficial [132]. Furthermore, acute inhibition of iNOS by antisense and pharmacological agents mitigated several pathological processes in SCI, including BSCB disruption [133]; acute molecular perturbation of iNOS via the antisense approach also enhanced neuronal preservation and functional recovery after SCI [134].…”

Section: Nitric Oxidementioning

confidence: 95%

Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury

et al. 2016

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The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

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“…This was followed by low speed centrifugation to obtain the supernatant, which was stored at -80°C (Maggio et al, 2012). The ELISA assay was performed according to manufacturer protocol once all the samples had been collected.…”

Section: Measurement Of Inflammationmentioning

confidence: 99%

Protective effect and mechanism of probucol in the treatment of spinal cord injury

Zhu¹,

Wang²,

Sun³

et al. 2015

Genet. Mol. Res.

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ABSTRACT.To investigate the effects of probucol on the treatment of spinal cord injury in rat, 80 rats were randomly divided into two groups of 40: a group treated with probucol and a control group. Allen's method was used to establish a rat model of spinal cord injury. After establishment, probucol (500 mg·kg -1 ·day -1 ) was intraperitoneally injected into the treatment group rats for 1 week, while the same amount of saline was used to treat the control group. On days 1, 7, 14, 21, and 28 after treatment, the function of rats' spinal cord was evaluated according to the Bresnahan locomotor rating scale. Serum protein and mRNA levels of the cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17] were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Protein levels of IFN-γ, TNF-α, IL-17, and the downstream markers signal transducer and activator of transcription (STAT)-1 and STAT-3 were measured using western blot. In addition, the oxidative stress-related parameters, superoxide dismutase (SOD) and malondialdehyde (MDA), were also measured. It was found that compared to control group, rats from the treatment group had significantly lower levels of IFN-γ, TNF-α, and IL-17 (P < 0.05) on days 1 and 7, as well as lower MDA levels and higher SOD activity on days 7, 21, and 28 (P < 0.05). In summary, probucol improved the recovery of locomotion function after spinal cord injury in rats through downregulation of inflammation and upregulation of anti-oxidative activity.

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Acute Molecular Perturbation of Inducible Nitric Oxide Synthase with an Antisense Approach Enhances Neuronal Preservation and Functional Recovery after Contusive Spinal Cord Injury

Cited by 21 publications

References 45 publications

Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury

Protective effect and mechanism of probucol in the treatment of spinal cord injury

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