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At least 19 recordsLinked to original sources
PubMed1997

Motor and sensory demyelinating mononeuropathy multiplex (multifocal motor and sensory demyelinating neuropathy): a separate entity or a variant of chronic inflammatory demyelinating polyneuropathy?

We report 16 patients with motor and sensory demyelinating mononeuropathy multiplex (MSDMM) or multifocal motor and sensory demyelinating neuropathy (MMSDN). These patients had the clinical pattern of motor and sensory mononeuropathy multiplex, electrophysiological evidence of demyelination including conduction block, and segmental demyelination in the sural nerve biopsy. Sixty per cent of patients had high CSF protein. Eighty per cent of patients showed good responsiveness to steroid treatment. Unlike multifocal motor neuropathy (MMN), MSDMM is characterized by a shorter course, sensory deficits and sensory nerve conduction abnormalities, absence of GM1 antibody in most patients tested, and a good response to steroid therapy. We believe that MSDMM represents a variant of chronic inflammatory demyelinating polyneuropathy (CIDP) and an intermediate link between CIDP and MMN.

Adolescent↗
PubMedDate not supplied

Generation of oligodendroglial progenitors in acute inflammatory demyelinating lesions of the rat brain stem is associated with demyelination rather than inflammation.

Remyelination is an extremely efficient process in the adult rodent central nervous system yet the source of new oligodendroglia that appear following primary demyelination is still subject to much debate. Using a reliable marker for oligodendroglial progenitor cells in vivo, the NG2 chondroitin sulphate proteoglycan, we have evaluated the response of endogenous NG2(+) cells in the adult rat brain stem and cerebellum to inflammatory demyelinating lesions in an experimentally induced animal model of multiple sclerosis (MS), antibody augmented experimental allergic encephalomyelitis (ADEAE). We have manipulated T-cell mediated EAE in Lewis rats by injecting in addition, either anti-myelin/oligodendroglial glycoprotein (MOG) antibodies to induce inflammatory demyelination, or non-specific mouse immunoglobulins to induce an inflammatory response without demyelination. We have examined the relationship of NG2(+) progenitor cells to microglia (OX-42(+)), astrocytes (GFAP(+)) and mature oligodendroglia (CNP(+)), in the normal and demyelinated CNS. In the normal CNS NG2-expressing cells are closely intermingled with other glia but represent a distinct cell population. A prominent inflammatory response, identified by the presence of large perivascular and periventricular accumulations of reactive OX42(+) macrophages/microglia, occurred in animals with ADEAE at 7-9 days post injection (DPI), coinciding with severe clinical symptoms. In animals injected with anti-MOG antibodies inflammation was followed by the appearance of large areas of demyelination at 11-14 DPI, at which point the animals had recovered clinically. The response of NG2(+) cells was different depending on whether the inflammation was accompanied by demyelination. In the presence of inflammation, NG2(+) cells responded by an increase in immunoreactivity and an alteration in their morphology, exhibiting enlarged cell bodies and an increased number of intensely stained processes. In areas of demyelination NG2(+) cells had fewer intensely stained processes reminiscent of progenitor cells seen during development. Quantitative analysis revealed a 3-fold increase in the number of NG2(+) cells in demyelinated lesions at 11 DPI, whereas no change was observed in areas of inflammation in the absence of demyelination. Mitotic figures were only seen in NG2(+) cells in areas of demyelination. NG2(+) cell numbers appeared to return to control levels following remyelination. These results suggest that endogenous oligodendroglial progenitors divide and/or migrate, in response to signals triggered by demyelinating rather than inflammatory events, to generate a large progenitor population sufficient to promote the rapid and successful remyelination observed in this model.

Animals↗
PubMed1983

In vivo demyelinating activity of sera from animals with chronic experimental allergic encephalomyelitis. Antibody nature of the demyelinating factor and the role of complement.

Sera from guinea pigs and rats with chronic experimental allergic encephalomyelitis were injected into the cerebrospinal fluid (CSF) of normal recipient rats. Guinea pig sera induced demyelination in the central and (or) peripheral nervous system, whereas injection of rat sera resulted in demyelination in the peripheral nervous system only. Control sera did not induce demyelination. Demyelinating activity in guinea pig sera was confined to the IgG-fraction; in rat sera the IgG- as well as the IgM-fraction were able to induce demyelination. The demyelinating activity was abolished when the sera were absorbed with with sensitising antigen (guinea pig spinal cord tissue) or when immunoglobulins were removed from the sera. When chronic EAE sera from rats were injected into the CSF of rats, complement was not required for the induction of demyeLination. The presence of complement, however, augmented the demyelinating activity. Decomplemented chronic EAE sera from guinea pigs failed to induce demyelination after injection into the CSF of rats. Injection of control and non-demyelinating or demyelinating EAE sera into the subarachnoid space of normal recipient rats induced a weak inflammatory response with increased numbers of large mononuclear cells in the meninges. It is discussed that in vivo a complex interaction of antibodies, complement and effector cells is responsible for induction of demyelination.

Animals↗
PubMed2001

Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is an autoimmune peripheral neuropathy and would be expected to benefit from corticosteroids. Non-randomised studies suggest that corticosteroids are often beneficial. OBJECTIVES: To evaluate the efficacy of corticosteroids for treating chronic inflammatory demyelinating polyradiculoneuropathy. SEARCH STRATEGY: Search of the Cochrane Neuromuscular Disease Group register for randomised trials of corticosteroids treatment for chronic inflammatory demyelinating polyradiculoneuropathy and enquiry from subject experts. SELECTION CRITERIA: Types of studies: All randomised or quasi-randomised trials Types of participants: All patients with chronic inflammatory demyelinating polyradiculoneuropathy who were diagnosed by an internationally accepted definition. Types of interventions: Treatment with any form of corticosteroid or adrenocorticotropic hormone. Types of outcome measures: PRIMARY OUTCOME MEASURE: Change in disability 12 weeks after randomisation. SECONDARY OUTCOME MEASURES: 1. Change in impairment 12 weeks after randomisation. 2. Change in maximum motor nerve conduction velocity or compound muscle action potential amplitude after 12 weeks. 3. Side effects of corticosteroids. DATA COLLECTION AND ANALYSIS: One author extracted the data and the other checked them. MAIN RESULTS: We identified one randomised controlled trial, an open study in which 19 corticosteroid treated patients showed more improvement in impairment than 16 untreated controls after 12 weeks. Experience from large non-randomised studies suggests that steroids are beneficial. REVIEWER'S CONCLUSIONS: A single randomised controlled trial with 35 participants provided weak evidence to support the common opinion derived from non-randomised studies that oral corticosteroids reduce impairment in chronic inflammatory demyelinating polyradiculoneuropathy. Corticosteroids are known to have serious long term side effects. The long term risks and benefits have not been adequately studied.

Adrenal Cortex Hormones↗
PubMed1994

The distribution of inflammatory demyelinated lesions in the central nervous system of rats with antibody-augmented demyelinating experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) has long been studied as an animal model of the human demyelinating disease Multiple Sclerosis. However, EAE induced in the Lewis rat by injection of myelin basic protein (MBP), or MBP-specific T-lymphocytes, is primarily an inflammatory condition of the central nervous system (CNS) with little or no demyelination. In EAE models in which demyelination does result, it is either not very widespread or is unpredictable in its degree and location. In this study we have produced antibody-augmented demyelinating EAE (ADEAE) in the Lewis rat by injection of activated MBP-specific T-lymphoblasts, followed by injection 4 days later of a monoclonal antibody against myelin/oligodendrocyte glycoprotein, an extrinsic protein of myelin. We have documented the extent and location of inflammatory cell infiltrates and demyelination throughout the CNS using histochemistry, immunofluorescence, and image analysis. Perivascular inflammatory infiltrates were seen in the deep cerebellar white matter and in the folia. Perivascular, periventricular, and subpial inflammation was widespread throughout the pons/medulla and at all levels of the spinal cord. Very little inflammation was apparent in the forebrain. MBP immunofluorescence demonstrated extensive areas of periventricular demyelination in the forebrain around the third ventricle. Both periventricular and perivascular lesions were commonly observed in the cerebellum and pons/medulla. The extent of demyelination in the spinal cord increased caudally with large confluent areas of subpial demyelination seen throughout the lumbar cord. The extensive and reproducible distribution of inflammatory demyelinating lesions in ADEAE provide the possibility to select areas of the CNS for more detailed analysis of the cellular changes that accompany demyelination and remyelination.

Animals↗
PubMed2005

Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part III. Paranodal internodal demyelination.

OBJECTIVE: The aim of this study is to investigate the potentials (intracellular, extracellular, electrotonic) and excitability properties (strength-duration and charge-duration curves, strength-duration time constants, rheobasic currents, recovery cycles) in progressively greater degrees of uniform reduction (20, 50 and 70%) of the paranodal seal resistance and myelin lamellae along the fibre length. METHODS: Three paranodally internodally systematically demyelinated cases (termed as PISD1, PISD2 and PISD3, respectively) are simulated using our previous double cable model of human motor nerve fibres. RESULTS: The results conform that in the more severely demyelinated cases, the intracellular potentials are with significantly reduced amplitude, prolonged duration and slowed conduction velocity, whereas the electrotonic potentials show abnormally greater increase in the early part of the hyperpolarizing responses. The extracellular potentials indicate increased polyphasia in the PISD3 case. The strength-duration time constants are shorter and the rheobasic currents higher in the demyelinated cases. In the recovery cycles, the demyelinated cases have less refractoriness, greater supernormality and less late subnormality than the normal case. CONCLUSIONS: The uniform reduction of the paranodal seal resistance and myelin thickness along the fibre length has significant effects on the potentials and excitability properties of the simulated demyelinated human motor fibres. Unexpectedly, the PISD fibres behave like paranodally demyelinated ones, since the myelin reduction increases slightly the effect of the paranodal demyelination on the nerve membrane properties. The study shows that the excitability properties in demyelinating neuropathies are much more largely determined by the paranodal changes than by the internodal changes. SIGNIFICANCE: The study provides new and important information about the pathophysiology of human demyelinating neuropathies.

Axons↗
PubMed1994

Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. VI. Potentiation of demyelination with and characterization of an immunopathologic CD4+ T cell line specific for an immunodominant VP2 epitope.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a relevant mouse model of multiple sclerosis. Demyelination is linked to persistent TMEV infection of the central nervous system and characterized by perivascular inflammatory mononuclear infiltrates and primary demyelination. Our previous results have shown that susceptibility correlates with the temporal development of chronic virus-specific delayed-type hypersensitivity (DTH) responses and suggest that inflammatory processes mediated by T cells specific for an immunodominant determinant on virus capsid protein 2 (VP2(74-86)) play a major immunopathologic role in SJL/J mice. In this study we have further defined the T cell-dependent nature and specificity of the demyelinating process in susceptible SJL/J mice by showing that thymectomized irradiated bone marrow-restored mice fail to develop chronic demyelination and that i.v. adoptive transfer of polyclonal TMEV-specific T cells before intracerebral infection with a suboptimal dose of the BeAn strain of TMEV led to increased incidence and accelerated onset of clinical disease. The data also show that demyelination is dependent on the activity of virus-specific CD4+ T cells because in vivo depletion with anti-CD4, but not anti-CD8, mAb led to significantly diminished incidence and severity of demyelination concomitant with a decrease in TMEV-specific DTH reactivity. In addition, the adoptive transfer of a TMEV-specific, DTH-mediating CD4+ I-A(s)-restricted Th1 line (sTV1) specific for the immunodominant VP2(74-86) epitope also led to increased incidence and accelerated onset of clinical disease only in TMEV-infected recipients. Collectively, the results of this and the companion paper demonstrate the highly significant immunopathologic contribution of CD4+ T cell responses specific for an immunodominant viral epitope to the chronic central nervous system demyelination observed in TMEV-infected SJL/J mice.

Animals↗
PubMed2005

Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part II. Paranodal demyelination.

OBJECTIVE: The purpose of the present investigation is to study the potentials and axonal excitability properties in progressively greater degrees of uniform paranodal demyelination of human motor nerve fibres. METHODS: Using our previous double cable model of human motor nerve fibre, 3 paranodally systematically demyelinated cases (termed as PSD1, PSD2 and PSD3) are simulated by an uniform paranodal resistance reduction (20, 50 and 77%) along the fibre length. RESULTS: Considerably reduced amplitudes, prolonged durations and slowed conduction velocities are obtained for the intracellular potentials of the PSD2 and PSD3 cases. In contrast, the electrotonic potentials show abnormally greater increase in the early part of the hyperpolarizing responses. The extracellular potentials indicate increased polyphasia in the PSD3 case. The strength-duration time constants are shorter and the rheobases higher in the demyelinated cases. In the recovery cycles, the demyelinated cases have less refractoriness, greater supernormality and less late subnormality than the normal case. CONCLUSIONS: The reduction of the paranodal seal resistance has significant effects on the potentials and axonal excitability properties of the simulated demyelinated human motor fibres. The obtained abnormalities in the potentials and excitability properties can be observed in vivo in patients with chronic inflammatory demyelinating polyneuropathy. SIGNIFICANCE: The study provides important information about the pathology of human demyelinating neuropathies.

Demyelinating Diseases↗
PubMed2006

Age increases axon loss associated with primary demyelination in cuprizone-induced demyelination in C57BL/6 mice.

Axon loss is recognised as a significant contributor to the progression of the disability associated with multiple sclerosis. Although evidence of axon damage is found in areas of chronic demyelination it is more frequently seen in association with acute demyelination. This study compares the incidence of axon degeneration associated with the areas undergoing demyelination in young adult (8-10 weeks) and aged (6-7 months) C57BL/6 mice in cuprizone intoxication; a widely used model of demyelination. The incidence of axon transection, as indicated by the presence of SMI 32 positive axonal spheroids, and evidence of axon loss in the medial corpus callosum, were significantly greater in aged mice, as was the magnitude of the macrophage and astrocyte response to demyelination. Aged C57BL/6 mice are thus more prone to axon degeneration in association with demyelination than young adult mice. A retrospective study indicated that the incidence of axon degeneration was much higher in C57BL/6 mice than in the Swiss albino mice used in the early cuprizone intoxication studies which were fed much higher doses of cuprizone. These results indicate both a genetic and age susceptibility to demyelination-associated axon transection.

Aging↗
PubMed2005

Criteria for demyelination based on the maximum slowing due to axonal degeneration, determined after warming in water at 37 degrees C: diagnostic yield in chronic inflammatory demyelinating polyneuropathy.

The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) is based on clinical and laboratory results and on features of demyelination found in nerve conduction studies. The criteria that are currently used to reveal demyelinative slowing in CIDP have several limitations. These criteria were only determined in lower arm and lower leg nerve segments, were not defined with respect to nerve temperature, and the relationship with distal compound muscle action potential (CMAP) amplitudes is unclear. The aim of our study was to determine criteria for demyelinative slowing for lower arm and leg segments as well as for upper arm and shoulder segments at a temperature of 37 degrees C, and to assess whether criteria have to be modified when the distal CMAP is decreased. Included were 73 patients with lower motor neuron disease (LMND), 45 patients with CIDP and 36 healthy controls. The arms and legs were warmed in water at 37 degrees C for at least 30 min prior to an investigation and thereafter kept warm with infrared heaters. The proposed criteria for demyelinative slowing were based on the maximum conduction slowing that may occur as a consequence of axonal degeneration and consisted of the upper boundary (99%) or the lower boundary (1%) of conduction values in LMND. In LMND, the maximum conduction slowing was different for arm and leg nerves and for segments within the arm nerves. Moreover, distal motor latency and motor conduction velocity were slower in nerves with distal CMAP amplitudes below 1 mV than in nerves with distal CMAP amplitudes above 1 mV. For these reasons, separate criteria were proposed for arm nerves, for leg nerves and for different segments within arm nerves, and more stringent criteria were proposed for distal motor latency and motor conduction velocity when the distal CMAP amplitude was below 1 mV. The diagnostic yield in CIDP was assessed using the nerve, and not the patient, as the unit of measurement. Thus, whether demyelinative slowing was present was determined for each nerve. Compared with other criteria, our criteria increased the specificity without affecting sensitivity. We conclude that the present criteria, based on the maximum slowing that may occur as a result of axonal degeneration, allow more accurate detection of demyelinative slowing in CIDP compared with other criteria. It should be emphasized that the proposed criteria can only be applied if the method of warming in water at 37 degrees C for at least 30 min is adopted.

Action Potentials↗
PubMed1991

[Demyelinating elements of demyelinated encephalopathy].

The myelin basic protein (MBPi) accounts for the main encephalitogenic antigen of the demyelinating encephalopathy, but other myelin elements also be noted by some articles. We tried to determine the relationship between W1 protein and the demyelinating encephalopathies. The 2',3'-cyclic nucleotide 3'-phospho-diesterase(CNPase, a gift from Dr. Yasuzo Tuskada) monoclonal antibody was used as a probe to study the W1 protein level in 5 different demyelinating encephalopathies and 2 normal adult brains with immunocytochemical technique. Two different demyelinating types of W1 protein level were found out. Type 1 showed the W1 protein level parallel with demyelinated feature in general pathology whereas the type 2 showed demyelinated in the general pathology but the W1 protein level was normal in the immunocytochemical study. Multiple system degeneration, Binswanger's disease and postvaccinal encephalopathy of type B encephalitis belong to type 1 and multiple sclerosis and Balo's concentric sclerosis belong to type 2. These results might indicate the different pathogenesis of demyelinating encephalopathies.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2001

Diagnostic value of sural nerve demyelination in chronic inflammatory demyelinating polyneuropathy.

The objective of the study was to determine the diagnostic value of features of demyelination and inflammation in sural nerve biopsy specimens of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The features of (i) demyelination, (ii) axonal de- and regeneration and (iii) inflammation were investigated by measuring the number of onion bulbs, g ratio (axon diameter/total nerve fibre diameter), myelinated nerve fibre density, number of clusters and endoneurial area in 21 patients with CIDP, as well as in 13 patients with chronic idiopathic axonal polyneuropathy (CIAP) and six autopsy controls. In addition, teased fibres were classified and lengths of internodes measured. We found no difference in demyelinating features between patients with CIDP and CIAP, as the percentage of fibres with segmental de- and remyelination and the number of onion bulbs were similar in both polyneuropathy groups. The g ratio, expected to be higher in a demyelinating disease due to thinner myelin sheaths, was significantly lower in CIDP than CIAP. Evidence for axonal degeneration was found in both CIDP and CIAP, as both showed a decrease in myelinated nerve fibre density. There was no evidence of endoneurial oedema in CIDP, as the endoneurial area did not differ between CIDP, CIAP and the autopsy controls. Although significant differences of features of demyelination, axonal degeneration and inflammation were found in sural nerve biopsy specimens, there was a considerable overlap between abnormalities in CIDP and CIAP patients. In the majority of patients, quantitative analysis of light microscopical abnormalities in sural nerves was similar in CIDP and CIAP. Therefore, a sural nerve biopsy is of limited diagnostic value in CIDP.

Adult↗
PubMed2002

Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination.

The primary target in multiple sclerosis (MS) is believed to be either myelin itself (myelinopathy) or the myelin-forming cell, the oligodendrocyte (oligodendrogliopathy). Although axonal injury occurs in MS, it is regarded as a secondary event to the myelin damage. Here, the lesion develops from myelin (outside) to the axon (inside) (Outside-In model). Recently, gray matter lesions and axonal injury in normal-appearing white matter have also been reported in MS. This raises two questions. 1) Is axonal injury exclusively secondary to myelin damage or from a direct insult to the axon or neurons (axonopathy)? (2) Is the injured axon regarded as only an end result of pathology or disease, or can axonal injury contribute to the spread of secondary damage, including demyelination? The former is raised from the fact that axonal damage has been reported in several virus infections, including human immunodeficiency virus, human T-lymphotropic virus 1, herpes simplex virus and coronavirus, which also cause demyelination. The latter possibility where axonal injury leads to other changes is raised from the rather unexpected similarity between spinal cord injury (SCI) and MS where axonal injury, oligodendrocyte apoptosis and demyelination are all present. In SCI, transection of axons leads to delayed oligodendrocyte apoptosis with secondary demyelination. Neurofilament immunostaining of spinal cord sections demonstrates that axonal injury with oligodendrocyte apoptosis also precedes demyelination in an animal model for MS, Theiler's murine encephalomyelitis virus infection. This implies that axonal injury could trigger demyelination. In this instance, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).

Animals↗
PubMed1990

Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. III. Failure of neuroantigen-specific immune tolerance to affect the clinical course of demyelination.

Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible mouse strains produces a chronic demyelinating disease in which mononuclear cell-rich infiltrates in the central nervous system (CNS) are prominent. Current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for TMEV-specific, major histocompatibility complex (MHC) class II-restricted delayed-type hypersensitivity (DTH) responses in which lymphokine-activated macrophages mediate bystander demyelination. The present study examined the possibility that concomitant or later-appearing neuroantigen-specific autoimmune T cell responses, such as those demonstrated in chronic-relapsing experimental allergic encephalomyelitis (R-EAE), may contribute to the demyelinating process following TMEV infection. T cell responses against intact, purified major myelin proteins (myelin basic protein (MBP) and proteolipid protein (PLP], and against altered myelin constituents were readily demonstrable in SJL/J mice with R-EAE, but were not detectable in SJL/J mice with TMEV-induced demyelinating disease. TMEV-infected mice also did not display T cell responses against the peptide fragments of MBP(91-104) and PLP(139-151) recently shown to be encephalitogenic in SJL/J mice. In addition, induction of neuroantigen-specific tolerance to a heterogeneous mixture of CNS antigens, via the i.v. injection of syngeneic SJL/J splenocytes covalently coupled with mouse spinal cord homogenate, resulted in significant suppression of clinical and histologic signs of R-EAE and the accompanying MBP- and PLP-specific DTH responses. In contrast, neuroantigen-specific tolerance failed to alter the development of clinical and histologic signs of TMEV-induced demyelinating disease or the accompanying virus-specific DTH and humoral immune responses. These findings demonstrate that TMEV-induced demyelinating disease can occur in the apparent absence of neuroantigen-specific autoimmune responses. The relationship of the present results to the immunopathology of multiple sclerosis is discussed.

Animals↗
PubMed1987

Evidence for central nervous system demyelination in chronic inflammatory demyelinating polyradiculoneuropathy.

It is unclear whether sporadic reports of concurrent multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent coincidence or whether these two demyelinating disorders are pathogenically related. We utilized the sensitivity of magnetic resonance imaging (MRI) in detecting central nervous system (CNS) lesions to investigate 16 patients with CIDP. Six of the 16 had periventricular, subcortical, and brainstem white matter lesions indistinguishable from those seen in MS. Three of these patients had definite clinical and laboratory evidence of MS; three others with abnormal MRIs had no findings indicative of CNS disease. Previous reports have indicated that a significant number of MS patients have peripheral nerve demyelination. Our study suggests that many CIDP patients have concurrent CNS demyelination. Taken together, these observations support the existence of a central-peripheral inflammatory demyelinating syndrome. Whether this combined demyelinating syndrome lies on a spectrum between MS and CIDP or is a separate pathogenic entity will require further investigation.

Adult↗
PubMed2002

Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model.

Metabolite changes in rat brain internal capsule (ic) area were monitored using volume localized in vivo proton MR spectroscopy (MRS) in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model of multiple sclerosis (MS), during the early phase (pre-acute) as well as during the complete pathological cycle of de- and re-myelination processes. The N-acetyl aspartate (NAA) peak showed reduction during the early phase of the lesion progression (demyelination) until day 10 and increased thereafter during remyelination. However, choline (Cho) and lipid resonances showed increased signal intensity during the early phase and decreased during remyelination. A progressive reduction of the NAA/Cr metabolite ratio in lesioned rats was observed during demyelination (up to day 10) compared with before lesion (control), and the value increased thereafter during remyelination (from day 15). During this period, however, the Cho/Cr ratio was a higher until day 10 and subsequently declined and was close to that calculated before lesion creation. The changes in NAA/Cr and Cho/Cr metabolite ratios correspond to changes in the individual metabolite peaks such as NAA and Cho. The increase in the intensity of the choline resonance during the early phase is indicative of the onset of an inflammatory demyelination process, and its rapid decrease thereafter is due to reduction in the inflammatory process associated with remyelination. Similarly, the increase in the intensity of lipids during the pre-acute stage of the lesion is attributed to active demyelination, which significantly decreased during remyelination. These MR results correlate well with the histology data obtained.

Animals↗
PubMed1991

The focally demyelinated rat fimbria: a new in vitro model for the study of acute demyelination in the central nervous system.

We have produced controlled local demyelination in Wistar rat fimbriae by injection of microliter quantities of the detergent lysophosphatidyl choline (LPC) stereotactically. Six to seven days later the hippocampus and fornix was dissected out en bloc and maintained in vitro for electrical evaluation of conduction through the damaged area. The tissue was then fixed for verification of the lesion by light and electron microscopy. All fimbriae showed a normal conducted action potential with a latency of 0.5 to 1.5 ms when the conduction distance was 4-5 mm. LPC-lesioned fimbriae also showed a later wave with a latency of 4-5 ms. This later wave had the same stimulus-response curve as the primary action potential, but was more sensitive to repeated stimulation. We interpret this wave as evidence of conduction into or through a demyelinated region. LPC-lesioned fimbriae also showed histological evidence of demyelination. This preparation provides an in vitro model for the study of acute local demyelination of central nervous system white matter, such as that induced by multiple sclerosis and other focally demyelinating diseases.

Acute Disease↗