Demyelination and Remyelination in Rat CNS Following Ethidium Bromide Injection

Yajima, Kunio; Suzuki, Kenji

doi:10.1097/00005072-197905000-00155

Cited by 50 publications

(72 citation statements)

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“…T wo injections of ethidium bromide (EBr) (each of 0.5 l of 0.5 mg /ml in saline) were made along a single track of a drawn-glass micropipette (tip lumen Ͻ10 m) inserted into the dorsal column through a small hole in the dura. EBr is a nucleic acid chelating agent that kills those cells which have their nuclei in the vicinity of the injection (Yajima and Suzuki, 1979;Blakemore, 1982). Because the cell bodies of the dorsal column axons are remote from the site of injection, the axons are spared and undergo segmental demyelination attributable to the death of their surrounding glial cells.…”

Section: Methodsmentioning

confidence: 99%

Conduction in Segmentally Demyelinated Mammalian Central Axons

1997

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The prominent symptoms associated with central demyelinating diseases such as multiple sclerosis (MS) are primarily caused by conduction deficits in affected axons. The symptoms may go into remission, but the mechanisms underlying remissions are uncertain. One factor that could be important is the restoration of conduction to affected axons, but it is not known whether demyelinated central axons resemble their peripheral counterparts in being able to conduct in the absence of repair by remyelination. In the present study we have made intraaxonal recordings from central axons affected by a demyelinating lesion, and then the axons have been labeled ionophoretically to permit their subsequent identification. Ultrastructural examination of 23 labeled preparations has established that some segmentally demyelinated central axons can conduct, and that they can do so over continuous lengths of demyelination exceeding several internodes (2500 m). Such segmentally demyelinated central axons were found to conduct with the anticipated reduction in velocity and a refractory period of transmission (RPT) as much as 34 times the value obtained from the nondemyelinated portion of the same axon; the RPT was typically prolonged to 2-5 times the normal value. We conclude that some segmentally demyelinated central axons can conduct, and we propose that the restoration of conduction to such axons is likely to contribute to the remissions commonly observed in diseases such as MS. Key words: demyelination; multiple sclerosis; axon; conduction properties; glia; ionophoresisMultiple sclerosis (MS) is a disease of the C NS in which affected central axons often lose one or more internodes of their myelin sheath; the continuity of the axon through the lesion is frequently maintained, although degeneration becomes more prominent as the disease progresses (McDonald, 1994). The disease is associated with symptoms such as paralysis, blindness, and numbness, which can be explained by conduction block in the relevant pathways. Such symptoms may spontaneously go into remission; however, the mechanisms underlying such remissions are not well understood. It is now clear that some demyelinated lesions are partially repaired by remyelination and that this phenomenon can be quite common and extensive in early lesions (Prineas et al., 1993a). Remyelination is known to restore secure conduction to central (Smith et al., 1979(Smith et al., , 1981Blight and Young, 1989;Felts and Smith, 1992;Honmou et al., 1996) and peripheral (Saida et al., 1980;Smith and Hall, 1980;Sedal et al., 1983;Shrager, 1988) demyelinated axons, and it is reasonable to believe that conduction in remyelinated central axons will contribute to remissions; however, even where remyelination occurs in MS, it may be temporary (Prineas et al., 1993b), and persistently demyelinated lesions are a common feature of the disease. It is known that some of these persistently demyelinated lesions are clinically silent, i.e., they do not produce symptoms (Ghatak et al., 1974;Phadke and Best, 1983; f...

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Section: Methodsmentioning

confidence: 99%

Conduction in Segmentally Demyelinated Mammalian Central Axons

1997

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“…The injection of a 0.1% eB solution in the cisterna pontis determines the disappearance of local astrocytes and the formation of primary demyelinating lesions with the invasion of schwann cells and lymphocytes in the damaged area 16 . The intracisternal injection of eB in sprague-dawley rats determined oligodendrocyte degeneration 72 hours after drug injection and, 6 days after the surgical procedure, the center of the lesion had most of the axons demyelinated with oligodendrocyte disappearance and the presence of abundant macrophage infiltrate containing myelin debris 17 .…”

Section: Fig 2 Scores Across Days In Groups 1 Andmentioning

confidence: 99%

“…The demyelinated animals made fewer steps than the non-demyelinated ones. some studies report that the animals receiving eB injection develop motor deficits until day 31, but not anymore on day 35 after lesion 4,17 . The presence of these deficits may contribute to the decrease in the number of footsteps taken by the demyelinated animals, probably due to motor limitation during locomotion and uncertainty to perform the steps needed to complete the elevated beam traverse.…”

Section: Fig 2 Scores Across Days In Groups 1 Andmentioning

confidence: 99%

Effects of aquatic exercises in a rat model of brainstem demyelination with ethidium bromide on the beam walking test

Nassar

Bondan

Alouche

2009

Arq. Neuro-Psiquiatr.

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-Multiple sclerosis is a demyelinating disease of the central nervous system associated with varied levels of disability. The impact of early physiotherapeutic interventions in the disease progression is unknown. We used an experimental model of demyelination with the gliotoxic agent ethidium bromide and early aquatic exercises to evaluate the motor performance of the animals. We quantified the number of footsteps and errors during the beam walking test. The demyelinated animals walked fewer steps with a greater number of errors than the control group. The demyelinated animals that performed aquatic exercises presented a better motor performance than those that did not exercise. Therefore aquatic exercising was beneficial to the motor performance of rats in this experimental model of demyelination.Key Words: multiple sclerosis, demyelination, aquatic exercises, physiotherapy.Efeitos de exercícios aquáticos no desempenho motor de ratos submetidos a um modelo de desmielização com brometo de etídio resumo -A esclerose múltipla é uma doença desmielinizante do sistema nervoso central que se associa a graus variados de incapacidade. Não se sabe se a realização de intervenções fisioterapêuticas precoces têm impacto na evolução dessa doença. Utilizamos um modelo experimental de desmielinização com o gliotóxico brometo de etídio e a aplicação de exercícios aquáticos precoces para avaliar o desempenho motor dos animais. Foram quantificados o número de passos e os erros executados durante a travessia da barra elevada. os animais desmielinizados apresentaram menor número de passos e maior quantidade de erros em comparação aos grupos-controle. os animais desmielinizados que realizaram exercícios aquáticos apresentaram melhor desempenho motor que os animais desmielinizados que não foram submetidos à intervenção. Portanto, a realização de exercícios aquáticos mostrou-se benéfica no desempenho motor dos animais submetidos ao modelo experimental do brometo de etídio.PAlAvrAs-chAve: esclerose múltipla, desmielinização, exercícios aquáticos, fisioterapia.

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“…Following a demyelinating insult, it is known that CNS axons can be remyelinated [21][22][23]. This remyelination can completely restore CNS conduction [24,25].…”

Section: Author Manuscript Author Manuscriptmentioning

confidence: 99%

“…That alterations in hindlimb stride width were not observed during the progressive demyelinating phase of disease (within 100 d.p.i.) in two independent time courses with susceptible SJL/ J mice demonstrates the specificity of this functional assay in detecting axonal loss rather than demyelination (or total spinal cord lesion load).Following a demyelinating insult, it is known that CNS axons can be remyelinated [21][22][23]. This remyelination can completely restore CNS conduction [24,25].…”

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confidence: 95%

Assessment of hindlimb gait as a powerful indicator of axonal loss in a murine model of progressive CNS demyelination

et al. 2000

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Identifying the role of axonal injury in the development of permanent, irreversible neurologic disability is important to the study of central nervous system (CNS) demyelinating diseases. Our understanding of neurologic dysfunction in demyelinating diseases and the ability to assess therapeutic interventions depends on the development of objective functional assays that can noninvasively measure axonal loss. In this study, we demonstrate in a murine model of progressive CNS demyelination that assessment of the hindlimb width of stride provides a powerful indicator of axonal loss and can dissociate between deficits induced by demyelination versus axonal loss. KeywordsMultiple sclerosis; Neurodegeneration; Oligodendrocyte; Footprint; Theiler's virus; Motor function Central nervous system (CNS) demyelinating diseases can result in axonal damage that may contribute to irreversible neurologic dysfunction [1,2]. The role of this axonal damage in the development of neurologic dysfunction is not completely understood. Theiler's murine encephalomyelitis virus (TMEV) induces a chronic inflammatory CNS demyelinating disease in spinal cords of susceptible mice that is pathologically similar to human multiple sclerosis [3][4][5][6]. Intracerebral infection with TMEV results in a biphasic disease that is characterized by an acute infection of the gray matter followed by demyelination of the spinal cord [7]. The virus is cleared from the gray matter within 20 days and establishes chronic persistence in the brainstem and spinal cord white matter. We have demonstrated previously that medium and large axons are lost during the late, chronic stage (~180 days post-infection) of this demyelinating disease [8], and we have hypothesized that this fiber loss contributes significantly to disruptions in motor coordination at this time point.Because both demyelination and axonal loss can contribute independently to neurologic dysfunction during the course of a progressive CNS demyelinating disease, it is important to * Corresponding author. Tel.: +1-507-284-4663; fax: +1-507-284-1637. rodriguez.moses@mayo.edu (M. Rodriguez For gait analyses, male / female SJL/ J (prototypic susceptible strain; n=34) and C57BL/6J (prototypic resistant strain; n=20) mice were purchased from The Jackson Laboratories (Bar Harbor, ME, USA) and injected intracerebrally at 8 weeks of age with 2×10 6 PFU of TMEV in a 10-μl volume (n=10 mice per strain) or 10 μl PBS (n=10 mice per strain) to serve as sham-infected controls. Forelimb and hindlimb width of stride was measured, as described previously [19]. Forelimb and hindlimb paws were painted with red and blue nontoxic paint (RoseArt Industries; Livingston, NJ). The mice were then expected to walk along a strip of white paper. A minimum of five prints per mouse were digitized with a color scanner and measured using a program written for the KS400 image analysis software (Kontron Elektronik, Munich, Germany). The program automatically calculated the length and width of stride for each measured step. Foreli...

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Demyelination and Remyelination in Rat CNS Following Ethidium Bromide Injection

Cited by 50 publications

References 0 publications

Conduction in Segmentally Demyelinated Mammalian Central Axons

Conduction in Segmentally Demyelinated Mammalian Central Axons

Effects of aquatic exercises in a rat model of brainstem demyelination with ethidium bromide on the beam walking test

Assessment of hindlimb gait as a powerful indicator of axonal loss in a murine model of progressive CNS demyelination

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