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Results for “Remyelination”

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At least 19 recordsLinked to original sources
PubMed2025

Senescent-like microglia limit remyelination through the senescence associated secretory phenotype.

The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident in multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesions after injury, and treatments with senolytics enhances remyelination in young and middle-aged mice but not aged mice. In young mice, we observe the upregulation of senescence-associated transcripts, primarily in microglia and macrophages, after demyelination, followed by a reduction during remyelination. However, in aged mice, senescence-associated factors persist within lesions, correlating with inefficient remyelination. Proteomic analysis of the senescence-associated secretory phenotype (SASP) reveals elevated levels of CCL11/Eotaxin-1 in lesions of aged mice, which is found to inhibit oligodendrocyte maturation. These results suggest therapeutic targeting of SASP components, such as CCL11, may improve remyelination in aging and MS.

Animals↗
PubMed1975

Remyelination by Schwann cells of axons demyelinated by intraspinal injection of 6-aminonicotinamide in the rat.

Focal areas of primary demyelination were produced in the spinal cords of rats by means of local injections of 6-aminonicotinamide. Both astrocytes and oligodendrocytes underwent degeneration in the demyelinated area. Nearly all the demyelinated axons were remyelinated by Schwann cells; only a very small number of axons located adjacent to normally myelinated axons were remyelinated by oligodendrocytes. The glial limiting membrane was reconstituted around the ecge of the area remyelinated by Schwann cells. This experiment offers further evidence for an important role of astrocytes in controlling Schwann cell invasion of the central nervous system, and in addition suggests that astrocytes are also needed for oligodendrocyte remyelination to take place.

6-Aminonicotinamide↗
PubMed1979

The perineuronal satellite oligodendrocyte. A role in remyelination.

Demyelination was induced in the superior cerebellar peduncles of weanling mice by the administration of Cuprizone. Remyelination occurred when the animals were replaced on a normal diet. Perineuronal satellite oligodendrocytes in the periventricular gray were clearly seen to be remyelinating axons. This study demonstrates for the first time the role of these cells in remyelination, and raises the possibility that they may be involved in normal myelination of the central nervous system.

Animals↗
PubMed1979

Remyelination in multiple sclerosis.

Chronic plaques in central nervous system tissue fixed by in situ perfusion for electron microscopy were examined for evidence of remyelination in 2 patients with multiple sclerosis (MS). Fibers with abnormal central myelin sheaths of several types were found at the margins of most of the plaques studied. The most common of these were: (1) the presence of bare stretches of axon between contiguous internodes, (2) the presence of thin paranodes, (3) internodes which changed markedly in thickness along their length due to premature termination of superficial or deep myelin lamellae that ended as hypertrophic lateral loops, and (4) abnormally thin internodes which were of uniform thickness along their length, which were shorter than normal, and which terminated in the form of normal nodal complexes. The finding of internodes of the last type at the edges of many plaques indicates that remyelination by oligodendrocytes can occur in the adult human CNS and that it is common in some cases of MS, although limited in its extent.

Central Nervous System↗
PubMed1979

An autoradiographic study of cellular proliferation in remyelination of the central nervous system.

The proliferation and origin remyelinating oligodendrocytes was studied by light and electron miscrosopic autoradiography in the superior cerebellar peduncles of mice demyelinated by Cuprizone. In the early phases of demyelination, the cells undergoing mitotic activity were macrophages and astrocytes. In the later phases of demyelination, immature proliferating oligodendrocytes appeared; these differentiated into mature (dark) oligodendrocytes which were responsible for the remyelination of axons seen when animals were again placed on normal diets. The pattern of differentiation recapitulated that seen in developing oligodendrocytes in normal animals. Dark oligodendrocytes did not show mitotic activity. There was no mitotic activity in the subependymal cells around the fourth ventricle adjacent to the superior cerebellar peduncles. This study demonstrates the regenerative capacity of oligodendrocytes and their ability to carry out remeylination in the central nervous system.

Animals↗
PubMed1979

Demyelination and remyelination in the rat central nervous system following ethidium bromide injection.

Intracisternal injection of ethidium bromide induced status spongiosus with prominent degenerative changes in oligodendroglia in the subpial regions of the central nervous system of the rat. Chronologic investigation of the lesions has revealed that status spongiosus resulted in myelin degeneration, and by the 6th day postinjection many axons were demyelinated. At this time, numerous debris-filled phagocytic cells were observed among the totally naked axons. Vesicular transformation of myelin was the common degenerative change. Features suggestive of separation of myelin lamellae by phagocytic cells were also observed. In the demyelinated areas, oligodendroglial cells disappeared completely. By the 12th day postinjection, remyelination was apparent and numerous active oligodendroglia appeared in association with thinly myelinated axons. Some central nervous system axons were myelinated by Schwann cells. These patterns of demyelination and remyelination observed in ethidium bromide-treated rats were compared with those observed in other demyelinating conditions of varied etiology such as experimental allergic encephalomyelitis, diphtheria toxin, or lysolecithin injection and cuprizone intoxication.

Animals↗
PubMed2026

Effects of quetiapine on cognitive functioning in schizophrenia: evidence for the remyelination hypothesis?

Postmortem findings, neuroimaging data, and in-vitro models suggest a decrease in number and density of oligodendrocytes is driving cognitive deficits in schizophrenia (SCZ). Second-generation antipsychotics are discussed to improve oligodendrocyte dysfunction with most conclusive evidence available for quetiapine (QET). We postulate that sustained QET treatment leads to cognitive improvement in SCZ, particularly, in tests with high demands for working memory function. We further hypothesize that these effects are moderated by polygenic factors associated with hippocampus-related brain volumes, general white matter integrity, and/or oligodendroglia-related SCZ risk. Using data of the prospective PsyCourse study, we identified 166 patients with SCZ spectrum disorder receiving QET at one or two consecutive visits plus 166 matched patients without QET. Polygenic scores were calculated for subcortical brain volumes, measures of white matter integrity, and for cell type-specific genetic SCZ risks. QET treatment was consistently associated with improved cognitive function independent of time, specifically, in tests with high, but not with low to medium working memory load. Polygenic analyses did not reveal significant moderation effects. In contrary, low genetic SCZ risk specific for genes related to human oligodendrocyte function was associated with higher cognitive performance independent from QET. While we observed improved cognitive performance under QET in high working memory tests, we did not find evidence that polygenic factors associated with hippocampus-related brain volumes, white matter integrity, or oligodendroglia-related SCZ risk moderate this association. Thus, our tentative findings do not provide evidence for the hypothesis that polygenic estimates of hippocampal remyelination capacities influence the association between QET and cognitive performance in SCZ.

Humans↗
PubMed2025

Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome.

Oligodendrocytes, the myelinating cells in the central nervous system, are implicated in several neurological disorders marked by dysfunctional RNA-binding proteins (RBPs). The present study aimed at investigating the role of hnRNP A1 in the proteome of the corpus callosum, prefrontal cortex, and hippocampus of a murine cuprizone-induced demyelination model. Right after the cuprizone insult, we administered an hnRNP A1 splicing activity inhibitor and analyzed its impact on brain remyelination by nanoESI-LC-MS/MS label-free proteomic analysis to assess the biological processes affected in these brain regions. Significant alterations in essential myelination proteins highlighted the involvement of hnRNP A1 in maintaining myelin integrity. Pathways related to sphingolipid and endocannabinoid signaling were affected, as well as the synaptic vesicle cycle and GABAergic synapses. Although behavioral impairments were not observed, molecular changes suggest potential links to memory, synaptic function, and neurotransmission processes. These findings enhance our understanding of the multifaceted roles of hnRNP A1 in the central nervous system, providing valuable insights for future investigations and therapeutic interventions in neurodegenerative and demyelinating diseases.

Animals↗
PubMed1979

Recurrent demyelination in chronic central nervous system infection produced by Theiler's murine encephalomyelitis virus.

A morphologic study of demyelination produced by Theiler's encephalomyelitis virus (TMEV) infection in C3H/He mice was performed. Demyelination in this strain of mouse was less intense and had a milder gliomesodermal response than that observed in SJL mice. As early as 80 days after infection numerous remyelinated axons were present in C3H/He mice, and later, extensive remyelination was observed and was mainly by Schwann cells. About one-third of remyelinated plaques showed recurrent demyelinating activity at 200 days. The best evidence of recurrent demyelination was the loss of myelin by abons which had been previously remyelinated by Schwann cells. In addition, acute areas of demyelination were also seen in spinal cords which contained chronic or quiescent plaques. The demonstration of recurrent demyelination in TMEV infection is important for it increases the relevance of this model to multiple sclerosis (MS). In addition TMEV infection of C3H/He mice appears to be an excellent model for further studies of Schwann cell remyelination and recurrent demyelination in the central nervous system (CNS).

Animals↗
PubMedDate not supplied

Histology and ultrastructure of alterations in neuropathy.

Histologic findings are described in nerves from men exposed to lead, from patients with discrete clinical signs of peripheral neuropathy, and from controls. Every nerve from control subjects showed an abnormality (paranodal remyelination, segmental remyelination, or regeneration) in teased fibers. The only histologic alteration in eight lead-exposed males without signs or symptoms of neuropathy was a slightly increased incidence of paranodal remyelination. Sixteen patients with discrete neurologic symptoms and signs had a loss of large myelinated fibers and an increased incidence of regenerated fibers among teased fibers. Electron microscopy of unmyelinated fibers showed an increased occurrence of Schwann-cell processes, of fibers undergoing degeneration, and of Schwann-cell subunits with many profiles as the earliest signs of abnormality. Clinically mild neuropathies may exhibit advanced regeneration in the case of unmyelinated fibers. The earliest sign of degeneration in myelinated fibers was a diminution in the number of axonal organelles.

Adult↗
PubMed1979

Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats. A preliminary report.

About 30% of weanling rats inoculated with JHM virus developed a subacute demyelinating encephalomyelitis (SDE) 3 weeks after inoculation (a.i.). From the remaining animals, 5% displayed overt neurological signs 3, 6, and 8 months a.i. Animals with and without clinical signs 6-8 months a.i. were morphologically examined. Fresh demyelinating lesions could be demonstrated in paralyzed animals. Viral antigen was demonstrated and infectious JHM virus could be recovered from one animal which developed clinical signs at 3 months a.i. In one animal with clinical onset of 8 months a.i. completely remyelinated areas as well as recent demyelinating lesions were observed, suggesting a recurrence of the disease process. Remyelinated areas were also found in 40% of clinically silent animals. The morphology of the late onset of the demyelination was similar to that occurring in SDE. Remyelination consisted of both CNS and PNS-type. This animal model offers the possibility to investigate the virus-host relationship which is responsible for the induction of a demyelinating process after a long incubation period.

Animals↗
PubMed1978

Lesions in the cat spinal cord following local injections of 6-aminonicotinamide.

Lesions were made in the spinal cord of cats by means of local injections of 6-aminonicotinamide. The concentration needed to induce primary demyelination also caused extensive axonal death. In the early stages following injection there was evidence of astrocyte and oligodendrocyte destruction and with longer survival times most of the surviving demyelinated axons were remyelinated by Schwann cells. This experimental system indicates that Schwann cell remyelination of central axons follows astrocyte destruction, but it was not considered a suitable model system for the study of cellular relationships in remyelination because of the extensive concomitant axonal damage.

6-Aminonicotinamide↗
PubMed1977

Regeneration of oligodendroglia during recovery from demyelinating disease.

Infection of mice with the JHM strain of mouse hepatitis virus causes demyelination as a result of a cytolytic infection of oligodendroglia. In recovery, animals show remyelination, which could result either from surviving oligodendrocytes extending their territory or by generation of new oligodendroglia. Electron microscopic autoradiographic studies with 3H-labeled thymidine demonstrate that the cells associated with remyelination are newly generated oligodendroglia.

Animals↗
PubMed1977

The role of Schwann cells in paradoxical regeneration in the axolotl.

The experiments described here examine further the conditions under which paradoxical regeneration occurs and provide support for the hypothesis that a proximal migration of Schwann cells is responsible for the phenomenon. When only the hand is shielded from irradiation and the limb is denervated, amputation through the forearm or upper arm sometimes results in regeneration. The effects of variation in the time interval between denervation and amputation, the level of amputation and the method and number of denervations on the incidence of regeneration were investigated. The presence or absecce of viable Schwann cells at the amputation plane was deduced from the remyelination of nerves under conditions which do or do not permit paradoxical regeneration. The nerves of totally irradiated and denervated limbs remain unmyelinated following regrowth of axons and such limbs do not regenerate after amputation. When only the hand was shielded from irradiation before the limbs were denervated, the new axons became completely remyelinated and some of these limbs regenerated when amputated. It is suggested that under these conditions Schwann cells can migrate proximally and can then proliferate further to form a blastema, since they would be the only unirradiated tissue present at the amputation plane.

Ambystoma↗
PubMed1977

Lead neuropathy. 1) Morphometry, nerve conduction, and choline acetyltransferase transport: new finding of endoneurial edema associated with segmental demyelination.

Morphometric and pathologic studies along the length of the peripheral nervous system were obtained in groups of rats fed 4% lead carbonate for 3 and 6 months and in match-fed controls. The number and diameter histograms of L6 cytons of spinal ganglia and of myelinated fibers of proximal and distal portions of peroneal and sural nerve were not significantly different from the control groups. On the other hand, segmental demyelination occurred approximately as frequently in proximal as in distal parts of nerves. At 3 months approximately 1/3 of teased myelinated fibers showed changes of segmental demyelination (Condition C), or of remyelination after segmental demyelination (Condition F) or of both segmental demyelination and of remyelination (Condition D), while at 6 months more than 4/5ths of fibers showed these changes. As expected, regression lines of axonal area on number of lamellae of myelin, were less steep in nerves of rats fed on lead for 6 months as compared to controls. Axonal transport of choline acetyltransferase in lead neuropathy did not differ from that in control rats. As expected from the studies of others, conduction velocity of myelinated fibers of caudal nerve were low. A new finding was the often quite striking increase of transverse fascicular area of peripheral nerves. This was due to edema which appeared to develop at about the time of onset os segmental demyelination. Although the edema may be an epiphenomenon, it could be an important observation bearing on the development of lead neuropathy. It would be important to know next whether or not the blood nerve barrier is altered in lead neuropathy.

Animals↗
PubMed1975

Mouse hepatitis virus-induced recurrent demyelination. A preliminary report.

Four-week-old BALB/c mice inoculated intracerebrally with the JHM strain of mouse hepatitis virus developed an acute demyelinating disease followed by apparent recovery with remyelination. When surviving mice were examined 16 months later, small areas of active demyelination were still present. This is the first reported example, to our knowledge, of an experimental viral infection in which acute demyelination with recovery is followed by persisting or recurring demyelination.

Animals↗
PubMed1975

Axonal degeneration in sodium cyanate-induced neuropathy.

Two patients with sickle cell disease who had been maintained on sodium cyanante therapy for periods of 440 and 600 days on dosages up to 44 and 41 mg/kg per day developed a motor and sensory neuropathy. In both, definite abnormalities of myelinated and unmyelinated fibers were found. In one, the predominant abnormality of myelinated fibers was segmental demyelination and remyelination; in the other, there were histological features typical of axonal degeneration. It seems unlikely that the brunt of the metabolic derangement was on Schwann cells in the first case and on the nerve cell in the second. Probably, in both cases, the primary effect was on the nerve, with Schwann cell changes being concomitant or secondary. The clustered distribution of the segmental demyelination favors the latter.

Adult↗