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PubMed2007

Lack of correlation between cortical demyelination and white matter pathologic changes in multiple sclerosis.

BACKGROUND: Histopathologic studies have shown that subpial cortical demyelination is extensive in chronic multiple sclerosis (MS). OBJECTIVE: To study whether subpial cortical demyelination in MS is associated with focal or diffuse white matter (WM) pathologic features on magnetic resonance imaging (MR imaging). DESIGN: Comparison of postmortem MR imaging findings with histopathologic findings. SETTING: Brain donations from a general community. PATIENTS: Three patients with MS with extensive cortical demyelination and 3 patients with minor cortical demyelination were selected from an MS autopsy data set. The postmortem MR imaging and histopathologic data of the patients were compared. MAIN OUTCOME MEASURES: Two observers blinded to the results of each other assessed the presence, extent, and distribution of focal and diffuse pathologic changes in WM by MR imaging and by histopathology. RESULTS: Extensive subpial demyelination was not associated with a significant increase in the area of focal and diffuse WM pathologic changes as assessed by Luxol fast blue histochemistry or by MR imaging or with the presence or extent of juxtacortical abnormalities on MR imaging. CONCLUSIONS: The lack of association of MS gray matter demyelination with diffuse or focal WM changes indicates that gray matter demyelination in MS occurs largely independent of WM pathologic changes. The extent or distribution of WM abnormalities cannot be used to identify extensive cortical demyelination in the clinical setting.

Aged↗
PubMed1997

Local recruitment of remyelinating cells in the repair of demyelination in the central nervous system.

The distance over which remyelinating cells within surrounding intact tissue are stimulated to respond to a demyelinating lesion and migrate toward it is unknown. To address this issue we have conducted a series of experiments in which the generation of remyelinating cells in tissue surrounding a spontaneously repairing area of demyelination induced in the adult rat spinal cord is suppressed by exposure to X-irradiation. By regulating the area of X-irradiation relative to the length of the demyelinating lesion within dorsal white matter we have shown that remyelinating cells are not recruited over distances greater than 2 mm into areas of demyelination, implying that most of the remyelinating cells are locally generated. This result indicates that there is only a narrow rim of normal tissue surrounding an area of demyelination from which remyelinating cells can be recruited. The depletion of cells within this rim may account for the poor remyelination associated with large areas of demyelination and following repeated episodes of demyelination. We have also shown that, in contrast to Schwann cells, oligodendrocyte lineage cells recruited into lesions have a limited ability to rapidly repopulate large areas of demyelination. Attempts to enhance remyelination in situations where it fails should therefore focus on increasing the size of the surrounding area from which remyelinating cells can be recruited by augmenting the level of recruitment signal, and preventing premature differentiation of oligodendrocytes so as to maximize their migratory and proliferative potential.

Animals↗
PubMed2000

Model for focal demyelination of the spinal dorsal columns of transgenic MBP-LacZ mice by phototargeted ablation of oligodendrocytes.

Focal demyelination models provide powerful tools to study demyelination and remyelination in the central nervous system. In this report, we present a novel technique, which selectively targets oligodendrocytes within the spinal cord of transgenic mice to produce focal demyelination. Transgenic mice expressing the E. coli LacZ (beta-galactosidase) gene from the myelin basic protein promotor allowed for oligodendrocyte-specific cleavage of topically applied fluorescein-di-beta-galactopyranoside liberating photoactivatable fluorescein. Subsequent fluorescence illumination generated oxygen radicals that oxidized a second exogenous substrate, 3-amino-9-ethyl carbazole, to form a toxic precipitate within oligodendrocytes. Histochemical staining of the spinal cord dorsal columns 8 days following phototargeting revealed that the treated region no longer contained beta-galactosidase-positive cells. Focal demyelination of the dorsal columns was observed to a depth of 150 microm in transverse semithin plastic sections. Numerous bundles of naked axons interspersed with myelin, debris-laden macrophages, and reactive astrocytes were evident by electron microscopy. Remyelination of axons by both oligodendrocytes and invading Schwann cells was observed within the treated region 14 days after phototargeting. Newly generated oligodendrocytes were identified within the demyelinated region by their incorporation of bromodeoxyuridine. Thus, this novel focal demyelination protocol provides: (1) a method for selective targeted ablation of oligodendrocytes in vivo, (2) control over the extent of the demyelinated region, with (3) an environment that maintains its remyelination capacity. Phototargeted ablation of oligodendrocytes may therefore be a useful model for studying axon-glia interactions, axon regeneration within a demyelinated zone, and remyelination of axons.

Animals↗
PubMed2005

Astroglial-derived lymphotoxin-alpha exacerbates inflammation and demyelination, but not remyelination.

Tumor necrosis factoralpha (TNFalpha) and lymphotoxin-alpha (Ltalpha) are upregulated in and around multiple sclerosis plaques and are proposed to play a role during chronic inflammation in demyelinating disease. Despite the perceived detrimental role of these cytokines, human clinical trials inhibiting TNFalpha signaling has led to worsening of symptoms in multiple sclerosis (MS) patients. Our laboratory has verified a role for TNFalpha in the exacerbation of demyelination but, more importantly, has demonstrated a novel role for TNFalpha in reparative remyelination in a cuprizone-induced demyelination model. This may explain the worsening of symptoms experienced by MS patients. In view of the cross-talk in TNF family signaling, the aim of this study is to understand the role of Ltalpha in demyelination and remyelination in hopes of improving therapeutic strategies for MS. Using the same model, we show that mice lacking Ltalpha exhibit a delay in demyelination that is greater than that exhibited by TNFalpha null mice. In this model, Ltalpha is expressed primarily by astroglia. The delay in demyelination is accompanied by a delay in the loss of mature GSTpi-positive oligodendrocytes in Ltalpha-/- mice compared with wild-type mice. Ltalpha-/- mice have decreased numbers of microglia at the site of insult during demyelination, although the number of astrocytes present is similar between strains. In contrast to TNFalpha the lack of Ltalpha did not alter the time course of remyelination, or the number of mature oligodendrocytes during the remyelination phase. Since Ltalpha is detrimental in inflammation and demyelination, but not necessary for remyelination and repair, inhibiting Ltalpha signaling may represent a promising strategy to treat MS.

Animals↗
PubMed2006

Upregulation of the stress-associated gene p8 in mouse models of demyelination and in multiple sclerosis tissues.

Cuprizone-induced demyelination is a mouse model of multiple sclerosis (MS) as cuprizone-fed mice exhibit neuroinflammation and demyelination in the brain. Upon removal of cuprizone from the diet, inflammation is resolved and reparative remyelination occurs. In an Affymetrix GeneChip analysis, the stress-associated gene p8 was strongly upregulated (>10x) during cuprizone-induced demyelination but not remyelination. We verified this upregulation (>15x) of p8 in the CNS during demyelination by real-time polymerase chain reaction (PCR). This upregulation is brain-specific, as p8 is not elevated in the liver, lung, kidney, spleen, and heart of cuprizone-treated mice. We also localized the cellular source of p8 during cuprizone treatment, and further found elevated expression during embryogenesis but not in normal adult brain. Compared with wild-type controls, the death of oligodendrocytes in p8-/- mice is delayed, as is microglial recruitment to areas of demyelination. The corpus callosum of p8-/- mice demyelinates at a slower rate than wild-type mice, suggesting that p8 exacerbates CNS inflammation and demyelination. Enhanced expression of p8 is also observed in the spinal cords of mice with acute experimental autoimmune encephalomyelitis (EAE) induced by PLP139-151 peptide (10x). Increased expression is detected during disease onset and expression wanes during the remission phase. Finally, p8 is found upregulated (8x) in post-mortem tissue from MS patients and is higher in the plaque tissue compared with adjacent normal-appearing white and gray matter. Thus, p8 is an excellent candidate as a novel biomarker of demyelination.

Animals↗
PubMed1999

Enhanced axonal regeneration following combined demyelination plus schwann cell transplantation therapy in the injured adult spinal cord.

We have treated spinal cord injured rats with demyelination plus Schwann cell transplantation and assessed neurite outgrowth in a quantifiable model of axonal regeneration. Axonal injuries of differing severity were induced in the dorsal funiculus of adult rats using a micromanipulator-controlled Scouten knife. Demyelinated regions were produced so as to overlap with the injury site by the injection of galactocerebroside antibodies plus complement one segment cranial to the axonal injury site. Schwann cells were isolated from the sciatic nerve, expanded in vitro, and transplanted into the injury site 1 day later. Animals were killed after an additional 7 days. Schwann cells were evenly distributed throughout the region of demyelination, which extended 6-7 mm cranial to the axonal injury site. The severity of axonal injury was quantified by counting degenerate axons in transverse resin sections. The degree of axonal regeneration was assessed by an electron microscopic analysis of growth cone frequency and distribution relative to the site of axonal injury. Quantification of growth cones at a distance from the site of axonal injury indicated a strong linear relationship (P < 0.001) between the number of growth cones and the number of severed axons; the ratio of growth cones to severed axons was increased by 26.5% in demyelinated plus transplanted animals compared to demyelinated animals without a transplant. Furthermore, only the demyelinated plus transplanted animals contained growth cones associated with myelin in white matter immediately outside of the region of complete demyelination. Growth cones were absent in transplanted-only animals at a distance from the site of axonal injury. These findings indicate that combined demyelination plus Schwann cell transplantation therapy enhances axonal regeneration following injury and suggests that growth cones are able to overcome myelin-associated inhibitors of neurite outgrowth in the presence of trophic support.

Age Factors↗
PubMed1983

Analysis of humoral and cellular events and the role of lipid haptens during CNS demyelination.

In recent years, considerable interest has focused on the possibility that in experimental allergic encephalomyelitis (EAE), antigen other than myelin basic protein (MBP) may be required for the initiation of demyelination and for the development of exacerbating-remitting disease. Previous results from these laboratories have implicated a role for antibodies against galactocerebroside (GC) in initiating demyelination of central nervous system (CNS) tissue in vitro (8) and in vivo (9). We have now used the rabbit eye model to dissect further the role of antibodies in causing CNS demyelination. The results show: that in animals directly sensitized against GC, no spontaneous CNS lesion develops but primary demyelination is observed if a mononuclear inflammatory reaction is superimposed; that in rabbits sensitized against MBP, antiserum against GC causes enhanced demyelination; and that in normal animals, anti-GC serum initiates primary demyelination only when an inflammatory reaction is induced by supernatants of activated lymphocytes. Injection of anti-GC serum alone has no pathologic effect. These results suggest that antibodies against lipid haptens are capable of causing primary demyelination in the CNS in vivo but that effector cells provided by an inflammatory response are required. Thus, the development of the fully demyelinating lesion probably depends on both cellular and humoral mechanisms.

Animals↗
PubMed1990

Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated.

The neurotropic mouse hepatitis viruses (MHV), in particular strain JHM (JHMV or MHV-4), cause experimental central nervous system demyelination that pathologically resembles multiple sclerosis, an important human demyelinating disease. The mechanism of JHMV-induced demyelination remains unclear, though its tropism for oligodendrocytes had led to the belief that JHMV causes demyelination by direct lysis of these myelin-producing cells. However, several studies have also implicated the involvement of immune responses in the demyelinating process. In this communication, we present evidence that generalized immunosuppression with gamma irradiation prevents JHMV-induced demyelination, a finding that was not limited to a particular strain of JHMV or to one strain of mouse. In addition, significant paralytic-demyelinating disease was restored to infected, irradiated mice after the adoptive transfer of nylon wool nonadherent splenic cells and appeared to be restricted by the major histocompatibility complex (MHC). These observations indicate that the principal mechanisms of JHMV-induced demyelination are most likely immunopathological.

Animals↗
PubMed1990

Theiler's virus-induced demyelination in mice immunosuppressed with anti-IgM and in mice expressing the xid gene.

Intracerebral infection with Theiler's murine encephalomyelitis virus produces chronic immune-mediated demyelination in susceptible strains of mice. We examined the role of Ig in the pathogenesis of demyelination. In susceptible SJL/J mice (H-2s), suppression of B cell responses with IgG fraction of goat anti-mu (anti-mu IgG) from birth resulted in increased numbers and severity of demyelinating lesions in the spinal cord 35 days after infection. In contrast, treatment of resistant C57BL/10 (H-2b), C57BL/6 (H-2b), or B10.D2 (H-2d) mice with anti-mu IgG had no apparent effect since these mice did not develop demyelination or inflammation in the spinal cord following infection. Similar results were obtained with certain strains of B-cell deficient mice that exhibit the xid gene mutation. Male CBA/NJ (xid) showed increased meningeal inflammation and demyelination compared to male CBA/J mice. However, B6.CBAN, C3.CBAN, or C.CBAn mice showed no or minimal evidence of demyelination despite the presence of the xid mutation. In the SJL/J mouse, the majority of the humoral immune response to virus antigen was restricted to the IgG2b and IgM isotypes. These data indirectly support the hypothesis that immunoglobulins protect partially against development of virus-induced demyelination in susceptible but not resistant animals. In addition, the data argue strongly against the hypothesis that TMEV-induced demyelination is mediated predominantly by humoral autoimmune or humoral viral immune mechanisms.

Animals↗
PubMed2004

Oligodendrocytes and progenitors become progressively depleted within chronically demyelinated lesions.

To understand mechanisms that may underlie the progression of a demyelinated lesion to a chronic state, we have used the cuprizone model of chronic demyelination. In this study, we investigated the fate of oligodendrocytes during the progression of a demyelinating lesion to a chronic state and determined whether transplanted adult oligodendrocyte progenitors could remyelinate the chronically demyelinated axons. Although there is rapid regeneration of the oligodendrocyte population following an acute lesion, most of these newly regenerated cells undergo apoptosis if mice remain on a cuprizone diet. Furthermore, the oligodendrocyte progenitors also become progressively depleted within the lesion, which appears to contribute to the chronic demyelination. Interestingly, even if the mice are returned to a normal diet following 12 weeks of exposure to cuprizone, remyelination and oligodendrocyte regeneration does not occur. However, if adult O4+ progenitors are transplanted into the chronically demyelinated lesion of mice treated with cuprizone for 12 weeks, mature oligodendrocyte regeneration and remyelination occurs after the mice are returned to a normal diet. Thus, the formation of chronically demyelinated lesions induced by cuprizone appears to be the result of oligodendrocyte depletion within the lesion and not due to the inability of the chronically demyelinated axons to be remyelinated.

Animals↗
PubMed2002

Preservation of neurologic function during inflammatory demyelination correlates with axon sparing in a mouse model of multiple sclerosis.

Axonal injury has been proposed as the basis of permanent deficits in the inflammatory, demyelinating disease, multiple sclerosis. However, reports on the degree of injury are highly variable, and the responsible mechanisms are poorly understood. We examined the relationships among long-term demyelination, inflammation, axonal injury, and motor function in a model of multiple sclerosis, in which mice develop chronic, immune-mediated demyelination of the spinal cord resulting from persistent infection with Theiler's virus. We studied two strains of mice, inbred SJL/J and C57BL/6x129 mice deficient in beta(2)-microglobulin and therefore CD8 lymphocytes. After 8 months of disease, SJL mice had considerably worse motor function than beta(2)-microglobulin-deficient mice. Motor dysfunction correlated linearly with the extent of demyelinated lesions in the spinal cord (lesion load) within each strain, but no difference in lesion load was present between strains. Also, the extent of remyelination did not differ between strains. Instead, the disparity in motor deficits reflected differences in the integrity of descending neurons. That is, retrograde labeling of reticulospinal, vestibulospinal, and rubrospinal neurons, although reduced in all chronically diseased mice, was two to seven times higher in beta(2)-microglobulin-deficient mice. The labeling was superior in beta(2)-microglobulin-deficient mice despite the fact that lesion expanse and therefore the number of axons traversing lesions were similar in both strains. Thus, by all criteria axons were equivalently demyelinated in SJL and beta(2)-microglobulin-deficient mice, but the extent of axonal injury differed significantly. These results indicate that mechanisms of demyelination and axonal injury are at least partly separable, and are consistent with the hypothesis that cytotoxic CD8 lymphocytes may selectively injure demyelinated axons. Additionally, the data suggest that axonal injury obligatorily results from chronic inflammatory demyelination and significantly contributes to neurological deficits.

Animals↗
PubMed1982

Virus persistence and recurring demyelination produced by a temperature-sensitive mutant of MHV-4.

Mouse hepatitis virus type 4 (MHV-4, the JHM strain), a positive-strand RNA virus of the coronavirus family, is well documented as an inducer of acute and chronic demyelination in mice, as well as subacute demyelination in rats, due to a cytolytic infection of oligodendrocytes. However, experiments to explore the role of virus and host factors in the production of chronic or recurrent demyelinating disease have been limited because MHV-4 usually produces demyelination in conditions that frequently induce a fatal necrotizing encephalomyelitis. To circumvent this problem, we had made and selected mutant viruses that caused both a high incidence of demyelination and a low incidence of encephalitis-induced mortality. One such mutant, designated ts8, consistently caused acute demyelinating disease in over 90% of intracerebrally or intranasally (natural route of infection) inoculated, 4-5 week-old mice from several susceptible strains within 6-10 days. In addition, ts8 typically did not cause fatal necrotizing encephalitis, showing a low mortality (less than 5%). This reflected a unique tropism of ts8 for oligodendrocytes, but a limited one for neuronal cells. We now report that ts8 is also useful for inducing persistent infection of the mouse central nervous system (CNS). The histopathological correlate of this infection is chronic recurrent demyelination, and virus can be demonstrated ultrastructurally in intact oligodendrocytes, in the vicinity of demyelinated areas.

Animals↗
PubMed2005

The role of complement in immunological demyelination of the mammalian spinal cord.

STUDY DESIGN: Specificity of serum complement component to elicit immunological demyelination. OBJECTIVES: To assess the role of complement components and pathways in experimental immunological demyelination of the adult rat spinal cord. SETTING: ICORD, University of British Columbia, Vancouver, Canada. SUBJECTS: We used 32 adult male Sprague-Dawley rats, of approximately 220 g weight. METHODS: Rats received intraspinal infusions of demyelinating reagents, delivered by osmotic minipump, for a 7-day infusion at 0.5 microl/h. Reagents consisted of a polyclonal antibody to galactocerebroside and human serum complement. Complement sera deficient for a single component were used to assess the role of the alternative pathway, the classical pathway, and the membrane attack complex. Demyelination was assessed, at 7 days, ultrastructurally. RESULTS: Removal of C3 protein, common to classical and alternative complement pathways, or C4 protein, a classical pathway protein, resulted in no demyelination. However, complement deficient in Factor B, an alternative pathway protein, produced effective demyelination. Upon removal of C5 or C6, membrane attack complex proteins, demyelination was also observed. CONCLUSION: This suggests that the classical pathway is sufficient for the protocol to demyelinate the adult rat spinal cord, and that the membrane attack complex is also not required.

Animals↗
PubMed2003

Impaired remyelination and depletion of oligodendrocyte progenitors does not occur following repeated episodes of focal demyelination in the rat central nervous system.

It has been hypothesized that the progressive failure of remyelination in chronic multiple sclerosis is, in part, the consequence of repeated episodes of demyelination at the same site, eventually depleting oligodendrocyte progenitor cells (OPCs) and exhausting the remyelinating capacity. We investigated the effect of previous focal, ethidium bromide-induced demyelination of brain stem white matter (with intervening recovery) on the efficiency of the remyelination process during second and third subsequent episodes of demyelination, and the OPC response during a second episode of demyelination. Previous focal demyelinating lesions followed by recovery did not result in any retardation of the remyelination process, nor did they alter the proportion of Schwann cell versus oligodendrocyte remyelination. The OPC response during remyelination was quantified by in situ hybridization using a probe to platelet-derived growth factor-alpha receptor (PDGF alpha R), an OPC-expressed mRNA. Following recovery from focal, toxin-induced CNS demyelination, the OPC density returned to levels equivalent to those in normal white matter. Further more, there was no depletion of OPCs following repeated episodes of focal, toxin-induced CNS demyelination at the same site. These results indicate that repeated CNS demyelination, which has the opportunity to repair in the intervening period, is not characterized by impaired remyelination or depletion of OPCs.

Animals↗
PubMed2006

Spinal cord gray matter demyelination in multiple sclerosis-a novel pattern of residual plaque morphology.

The extent and pattern of gray matter (GM) demyelination in the spinal cord in multiple sclerosis (MS) has not been examined in detail. Human autopsy material was obtained from 36 MS cases and 12 controls. Transverse sections were taken from five levels of the spinal cord (upper cervical, lower cervical, upper thoracic, lower thoracic and lumbar levels) and the extent of GM and white matter (WM) demyelination evaluated using proteolipid protein immunohistochemistry (IHC). The proportion of the GM that was demyelinated (33%) was significantly greater than the proportion of demyelinated WM (20%) (P < 0.0001). Similarly, demyelination was more extensive in the GM than in the WM at each of the five cord levels. The extent of GM demyelination was not significantly different between the five cord levels while WM demyelination was greatest at the upper cervical level. Morphologically, the borders of a proportion of the GM plaques show a strict respect for the GM/WM boundary. We demonstrate that extensive demyelination occurs in the GM of the spinal cord in MS. Myelin protein IHC reveals a novel pattern of residual plaque morphology challenging previous work suggesting that MS plaques display a total disregard for anatomical boundaries.

Adult↗
PubMed1972

Internodal conduction in undissected demyelinated nerve fibres.

1. A new method is described for recording external longitudinal currents from single undissected nerve fibres in rat ventral roots. The method permits identification of the sites of fifteen or more successive nodes of Ranvier in a given single fibre and the measurement of internodal conduction times between them.2. Average internodal conduction time for normal ventral root fibres of internodal length between 0.75 and 1.45 mm is 19.7 +/- 4.6 (S.D.) musec at 37 degrees C. Internodal conduction time appeared to show a minimum for fibres of internodal length 1.0 mm.3. Ventral roots were demyelinated by focal application of diphtheria toxin. Although conduction is markedly slowed in demyelinated fibres, sites of inward membrane current remain spatially separated indicating that conduction remains saltatory to the point of conduction block rather than becoming continuous as in unmyelinated fibres.4. Slowing of conduction appears to be due to changes in the passive electrical properties of the internodal myelin. Evidence is presented suggesting that there is an increase in internodal capacitance and a decrease in internodal transverse resistance at internodes of demyelinated fibres; such changes would have the effect of delaying excitation at the nodes. The changes in passive electrical properties, which appear to be primarily in the vicinity of the nodes, would be consistent with the pathological changes observed in demyelinated fibres.5. Internodal conduction times in demyelinated fibres have ranged from normal (26 musec at 30 degrees C) to more than 600 musec. There is a great variation in internodal conduction time at successive internodes of a given single fibre; this presumably reflects the varying severity of demyelination of successive internodes.6. As in normal fibres, nodes of demyelinated fibres generate less current when excited by the second of two closely spaced impulses. This results in an increased internodal conduction time for the second impulse and, at a critically short interstimulus interval, conduction block of the second impulse.7. The increased refractory period of transmission of internodes with increased internodal conduction times is a consequence of the decreased ability of such internodes to sustain propagation in the face of small decreases in nodal current.8. During tetanic stimulation, increases in internodal conduction time are associated with corresponding decreases in nodal current generated by the node proximal to the internode in question.9. It is suggested that changes in the magnitude of the nodal current during repetitive activity are due to changes in transmembrane concentration gradients of sodium, the increased internodal conduction time and eventual conduction block during tetanic stimulation being caused by intracellular sodium accumulation.10. Intracellular sodium accumulation is also offered as the explanation for the post-tetanic depression seen in demyelinated fibres.

Action Potentials↗
PubMed1993

In vivo depletion of CD8+ T cells prevents lesions of demyelination in Semliki Forest virus infection.

Following intraperitoneal infection of BALB/c mice with the A7(74) strain of Semliki Forest virus, the virus spreads to the central nervous system (CNS) and initiates an acute inflammatory reaction which includes lesions of primary demyelination. This demyelination is dependent upon activated T lymphocytes. To determine whether CD4+ or CD8+ T cells are involved in the pathogenesis of the demyelination, we have investigated the course of infection in animals treated with monoclonal anti-CD4 or anti-CD8 antibodies. In the normal course of infection, virus was detectable in the brain by infectivity assay and in situ hybridization for up to 14 days. Antiviral immunoglobulin M (IgM) and all subclasses of IgG were produced. From day 10 to 21 postinfection lesions of inflammatory demyelination were present, most notably in the cerebellum and corpus callosum but also in other white matter tracts. Administration of anti-CD4 antibodies removed CD4+ cells from the spleen, prevented production of antiviral IgG, increased virus titers in the brain, and increased demyelination. Administration of anti-CD8 antibodies depleted CD8+ cells from the spleen and did not affect antiviral IgG synthesis or spread of brain virus but reduced CNS inflammatory responses and virtually abolished lesions of demyelination. Administration of both antibodies depleted both T-cell subsets from the spleen, prevented IgG antibody production, increased brain virus, and abrogated both CNS inflammation and lesions of demyelination. In conclusion, the CNS demyelination induced by Semliki Forest virus can be prevented by in vivo depletion of CD8+ T lymphocytes.

Alphavirus Infections↗
PubMed1981

Axonal lesions in acute experimental demyelination: a sequential teased nerve fiber study.

The relationship between axonal degeneration and primary demyelination was studied in isolated rat sciatic nerve fibers previously exposed to antiserum from rabbits with either experimental allergic neuritis or experimental allergic encephalomyelitis, or immunized with antigalactocerebroside antiserum. Continuous demyelination over one to eight or more internodes was seen in association with phagocytic cells or, later, with increased numbers of Schwann cells. Paranodal demyelination was prominent proximal ahd distal to the zone of continuous demyelination. Axonal degeneration affected 5 to 15% of myelinated fibers exposed to antiserum and was not related to the length of demyelination must proximal to the axonal changes. At times, there were seven or eight consecutive demyelinated internodes with no distal axonal degeneration; in contrast, one demyelinated internode was often associated with axonal degeneration beginning just distally. The inflammatory reaction could account for axonal degeneration in antiserum-mediated demyelination.

Animals↗