Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation

Kouhsar, Samaneh Sheikhi; Karami, Manizheh; Tafreshi, Azita Parvaneh; Roghani, Mehrdad; Nadoushan, Mohammadreza Jalali

doi:10.1016/j.brainres.2011.03.038

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…Increased serum and CSF concentrations of NO metabolites have been noted in MS patients, and have been suggested to cause damage to myelin and oligodendrocytes via lipid peroxidation (Speciale et al 2000;Kouhsar et al 2011). In our experiments, the decrease in iNOS synthesis observed in ginseng-treated mice correlated with a decrease in demyelination.…”

Section: Discussionsupporting

confidence: 63%

Effects of an aqueous extract of North American ginseng on MOG_(35–55)-induced EAE in mice

Bowie

Roscoe

Lui

et al. 2012

Can. J. Physiol. Pharmacol.

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, in which the release of reactive oxygen species by infiltrating immune cells contributes to demyelination. American ginseng ( Panax quinquefolius ) is a natural health product with numerous beneficial properties, including anti-inflammatory and anti-oxidant effects. The purpose of this study was to determine whether ginseng could influence the course of the disease experimental autoimmune encephalomyelitis (EAE), an animal model of MS. C57BL/6J mice were immunized with MOG((35-55)) peptide to induce EAE. After clinical disease appeared, mice received either oral doses of an aqueous extract of ginseng (150 mg/kg body mass), or the vehicle. Clinical symptoms were recorded, and spinal cord tissue samples were analyzed for pathological signs of disease. The aqueous extract of ginseng significantly decreased (i) clinical signs of EAE, (ii) levels of circulating TNF-α, and (iii) central nervous system immunoreactive iNOS and demyelination scores, without a change in other neuropathological measures. This study shows that an aqueous extract of ginseng may be able to attenuate certain signs of EAE, suggesting that it may be a useful adjuvant therapy for MS.

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Section: Discussionsupporting

confidence: 63%

Effects of an aqueous extract of North American ginseng on MOG_(35–55)-induced EAE in mice

Bowie

Roscoe

Lui

et al. 2012

Can. J. Physiol. Pharmacol.

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“…The authors have proposed that astrocyte-derived NO could be important for orchestrating further processes in MS. An abundant expression of iNOS in macrophages early in the course of the disease and before demyelization was also reported (49). The importance of iNOS expression in MS development is further substantiated by the fact that the injection of arginine [which acts both as an iNOS substrate and an up-regulator of iNOS mRNA (263)] into the rat brain provokes demyelination (248). The expression of iNOS in astrocytes most likely represents a key step in MS initiation, leading to further NO-provoked inhibition of ETC and the formation of a self-promoting redox loop ( Fig.…”

Section: No and H 2 O 2 From Endothelium Activate The Redox Cycle mentioning

confidence: 80%

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

Miljković

Spasojević

2013

Antioxidants & Redox Signaling

101

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The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy.

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“…22 Moreover, periventricular white matter lesions are associated with reduced memory speed and performance, and the severity of the lesion can predict the evolution of cognitive decline. 23 In rats, recognition memory is compromised after lesion of the corpus callosum, 24 whereas recognition 25 and spatial memory 26 are impaired after chronic hypoperfusion in mice, along with decreased callosal fiber density. When challenged with chronic hypoperfusion, stroke-prone spontaneously hypertensive rats show diffuse tissue damage (white and grey matter, cortex, and hippocampus) and severe deficit in Morris water maze.…”

Section: Discussionmentioning

confidence: 99%

Recognition Memory Impairments After Subcortical White Matter Stroke in Mice

Blasi

Ying

Balkaya

et al. 2014

Stroke

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T he vast majority of experimental stroke research has focused on animal models of large territorial infarction involving both cortical and subcortical grey and white matter. 1 However, 20% to 25% of strokes in humans are small, lacunarlike, involve subcortical white matter tracts, 2 are often recurrent, and may lead to cognitive decline, subcortical dementia, and major disability. 3 Moreover, white matter ischemic lesions are a main pathological manifestation of small vessel diseases, a subset of cerebrovascular alterations leading to stroke and cognitive decline. 4 Only a few experimental models investigating small white matter strokes have been reported. 5 Recently, Carmichael and collaborators 6 developed a model of selective white matter stroke by injecting the potent vasoconstrictor endothelin-1 into corpus callosum to create a small area of myelin and axonal degeneration. Although reproducibility has been a problem with this model, it generates a lesion confined to white matter and therefore offer advantages to other white matter injury models that in addition cause diffuse brain injury after global cerebral hypoperfusion.7 After adapting, improving, and extending this new experimental approach, we tested whether subcortical white matter ischemic injury is associated with cognitive impairment in wildtype (WT) mice. Furthermore, we tested whether a NOTCH3 gene deletion negatively affects tissue and functional outcome after selective white matter injury. NOTCH3 mutations are the most common cause of inherited strokes and vascular dementia in young and middle-aged adults. 8 We previously showed that NOTCH3 knockout mice seem especially vulnerable to ischemic injury after middle cerebral artery occlusion, probably because of vascular dysfunction and reduced collateral blood flow. 9 Here, we extended these findings to white matter susceptibility and provided a novel experimental approach to further dissect the relationship between genotype and ischemic phenotype in NOTCH3 mutants. Materials and MethodsExperiments were conducted according to protocols approved by the Animal Research Committee of Massachusetts General Hospital and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (see online-only Data Supplement).Background and Purpose-Small subcortical white matter infarcts are a common stroke subtype often associated with cognitive deficits. The lack of relevant models confined to white matter has limited the investigation of its pathophysiology. Here, we examine tissue and functional outcome after an ischemic lesion within corpus callosum in wild-type (WT) mice and in mice null for a gene, NOTCH3, linked to white matter ischemic injury in patients. Methods-WT and NOTCH3 knockout mice were subjected to stereotactic microinjections of the potent vasoconstrictor endothelin-1 at the level of periventricular white matter to induce a focal ischemic lesion. Infarct location was confirmed by MRI, and brains were examined for lesion size and histology; behavioral deficits were a...

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Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation

Cited by 5 publications

References 34 publications

Effects of an aqueous extract of North American ginseng on MOG_(35–55)-induced EAE in mice

Effects of an aqueous extract of North American ginseng on MOG_(35–55)-induced EAE in mice

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

Recognition Memory Impairments After Subcortical White Matter Stroke in Mice

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Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation

Cited by 5 publications

References 34 publications

Effects of an aqueous extract of North American ginseng on MOG(35–55)-induced EAE in mice

Effects of an aqueous extract of North American ginseng on MOG(35–55)-induced EAE in mice

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

Recognition Memory Impairments After Subcortical White Matter Stroke in Mice

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Product

Resources

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Effects of an aqueous extract of North American ginseng on MOG_(35–55)-induced EAE in mice

Effects of an aqueous extract of North American ginseng on MOG_(35–55)-induced EAE in mice