Further evidence for a role of nitric oxide in experimental allergic encephalomyelitis: aminoguanidine treatment modifies its clinical evolution

Pozza, Monica; Bettelli, Carla; Aloe, Luigi; Giardino, Luciana; Calzà, Laura

doi:10.1016/s0006-8993(99)02133-2

Cited by 28 publications

(18 citation statements)

References 45 publications

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“…In both Lewis and DA female rats, severity of EAE gradually increased, reaching its peak between 8 and 14 dpi and then partially recovering. In our experience (2,29), which was confirmed in this experiment, in the Lewis strain the disease relapses with lower severity in 60% of rats (Fig. 1).…”

Section: Resultssupporting

confidence: 81%

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Fernández

Giuliani

Pirondi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

124

101

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Chronic disabilities in multiple sclerosis are believed to be due to neuron damage and degeneration, which follow remyelination failure. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, one reason for demyelination failure could be the inability of oligodendrocyte precursor cells to turn into myelinating oligodendrocytes. In this study, we show that thyroid hormone enhances and accelerates remyelination in an experimental model of chronic demyelination, i.e., experimental allergic encephalomyelitis in congenic female Dark Agouti rats immunized with complete guinea pig spinal cord. Thyroid hormone, when administered during the acute phase of the disease, increases expression of platelet-derived growth factor ␣ receptor, restores normal levels of myelin basic protein mRNA and protein, and allows an early and morphologically competent reassembly of myelin sheaths. Moreover, thyroid hormone exerts a neuroprotective effect with respect to axonal pathology.neuroprotection ͉ multiple sclerosis ͉ oligodendrocyte precursor cells ͉ axonal pathology ͉ rat M ultiple sclerosis (MS) is a disorder of the central nervous system (CNS) that manifests as acute focal inflammatory demyelination with limited remyelination, usually culminating in chronic multifocal sclerotic plaques (1). Early axonal injury and loss followed by neuron distress (2) and death (3) occur in MS (4-6), accounting for brain and spinal cord atrophy. Irreversible axonal damage is an essential cause of nonremitting sensory, motor, and cognitive disabilities in MS (7). Although remyelination occurs in most experimental models of demyelination, this beneficial process is undoubtedly inadequate in MS. The reasons for this inadequacy are unknown, also because the oligodendrocyte precursor cells (OPCs), the cell population that is considered to be the most important source of remyelinating oligodendrocytes in the adult CNS (8-10), are present in early (fresh) demyelinating lesions in MS (11, 12).There are many possible speculative explanations for remyelination failure in MS (9, 10), including quantitatively inadequate recruitment and͞or differentiation of OPCs (13); axons not receptive to remyelination (14); and inappropriate support of growth factors by astrocytes and͞or other inflammatory cells (15), such as the extracellular microenvironment with regard to matrix proteins and adhesion molecules (16).Because the number of oligodendrocytes is greater than before demyelination in early MS, meaning that new oligodendrocytes are generated (17), another possibility is that OPCs are unable to turn into myelinating oligodendrocytes in chronic MS. Thus, extensive studies are under way to identify factors involved in OPC differentiation during remyelination. It is generally accepted that the process of remyelination represents a recapitulation of myelination during development, and so the key factors affecting the developmental maturation of OPCs into myelinating oligodendrocytes also should favor remyelination in the adult CNS. It ...

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Section: Resultssupporting

confidence: 81%

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Fernández

Giuliani

Pirondi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

124

101

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“…1A reports the schedule of the experiment and clinical neurological score of experimental animals. As previously described (17,19,23,24), the severity of EAE, as evaluated by strength deficit, gradually increased, reaching its peak between 10 and 14 days postimmunization (dpi), and then partially recovered. In our experience (24), which was confirmed in this experiment, the disease relapses in the Lewis strain with lower severity in 60% of animals.…”

Section: Resultssupporting

confidence: 52%

Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats

D’Intino

Paradisi

Fernández

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Clinical symptoms in multiple sclerosis include cognitive dysfunction. Difficulties in learning and remembering new information represent the most common cognitive deficit and are associated with a general and progressive brain pathology. Possible pathogenetic mechanisms for neuronal damage such as neuroprotective strategies are under active investigation also in experimental allergic encephalomyelitis, the most widely used experimental model for multiple sclerosis. In this paper we demonstrate that a selective deficit in learning and memory performance, as investigated by the Morris water maze test, is a consistent feature in rat encephalomyelitis, which correlates with a decline in choline acetyltransferase activity and nerve growth factor mRNA level in cerebral cortex, hippocampus, and basal forebrain. Treatment aimed to restore acetylcholine content through chronic administration of selective acetylcholinesterase inhibitors (rivastigmine and donepezil) restores cognitive performance, choline acetyltransferase activity, and nerve growth factor mRNA expression.choline acetyltransferase ͉ multiple sclerosis ͉ learning and memory ͉ water maze ͉ acetylcholinesterase inhibitors

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“…Elevated levels of these molecules have also been found in EAE, a widely studied model for MS, and the level of this induction correlates with disease severity and cellular infiltrate (17)(18)(19)(20)(21)(22). However, disruption of NO production in the EAE model has provided protection in some studies (23)(24)(25)(26)(27)(28) but exacerbated the pathology in other experiments (29 -32). Clearly, there are multiple factors determining the net effect of NO during demyelinating events, and NO may be proved to play distinct roles during different stages of inflammatory demyelination.…”

mentioning

confidence: 99%

The Protective Role of Nitric Oxide in a Neurotoxicant- Induced Demyelinating Model

Arnett

Hellendall

Matsushima

et al. 2002

The Journal of Immunology

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Demyelination is often associated with acute inflammatory events involving the recruitment-activation of microglia/macrophage, astrocytes, and leukocytes. The ultimate role of inflammatory products in demyelinating disease and in the survival of oligodendrocytes, the myelin forming cells, is unresolved. The current study examines the role of inducible NO synthase (iNOS)-derived NO in a neurotoxicant-induced model of demyelination. NO levels were greatly elevated in the midline corpus callosum during demyelination in genetically intact C57BL/6 mice, and this NO was due solely to the induction of iNOS, as the correlates of NO were not found in mice lacking iNOS. C57BL/6 mice lacking iNOS exhibited more demyelination, but did not display an increased overall cellularity in the corpus callosum, attributable to an unimpeded microglia/macrophage presence. An enhanced course of pathology was noted in mice lacking iNOS. This was associated with a greater depletion of mature oligodendrocytes, most likely due to apoptosis of oligodendrocytes. Microglia and astrocytes did not undergo apoptosis during treatment. Our results suggest a moderately protective role for NO during acute inflammation-association demyelination.

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Further evidence for a role of nitric oxide in experimental allergic encephalomyelitis: aminoguanidine treatment modifies its clinical evolution

Cited by 28 publications

References 45 publications

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats

The Protective Role of Nitric Oxide in a Neurotoxicant- Induced Demyelinating Model

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