Spinal cord multiple sclerosis lesions in Japanese patients: Schwann cell remyelination occurs in areas that lack glial fibrillary acidic protein (GFAP)

Itoyama, Yasuto; Ohnishi, Akio; Tateishi, Jun; Kuroiwa, Yoshigoro; Webster, H. F. de

doi:10.1007/bf00687001

Cited by 70 publications

(54 citation statements)

References 33 publications

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“…That study demonstrated that astrocytes expressing AQP4 were more abundant at the periphery of demyelinated plaques as compared with the center of the lesion (Aoki-Yoshino et al 2005). Another important finding in our case of NMO was the relatively preserved MBP-stained myelinated fibers in the lesions, even in the regions near the cavitary lesions where astrogliosis was usually impaired (Itoyama et al 1985). These findings, especially a loss of AQP4 in the lesions, strongly suggest that NMO belongs to a distinct disease entity from MS.…”

Section: Discussionsupporting

confidence: 62%

Loss of Aquaporin-4 in Active Perivascular Lesions in Neuromyelitis Optica: A Case Report

Misu

Fujihara

Nakamura

et al. 2006

Tohoku J. Exp. Med.

110

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Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and transverse myelitis. In Japan, NMO has been named optic-spinal multiple sclerosis (OSMS) and it has been thought to be a subtype of multiple sclerosis (MS). However, several clinical and laboratory findings suggest NMO or OSMS is distinct from MS. Recently, the disease-specific antibody (NMO-IgG) was found in the serum from NMO patients, and its target antigen was identified as aquaporin-4 (AQP4) water channel protein which is mainly expressed in astroglial foot processes. However, the pathogenetic role of AQP4 in NMO remains unknown. We herein report a typical case of NMO in which immunohistochemical analysis showed a lack of AQP4 in the spinal cord lesions. The loss of AQP4 was evident in the central gray matter, especially in the perivascular lesions where immunoglobulins and complements were deposited, and glial fibrillary acidic protein (GFAP) staining was weak in those lesions. However, GFAP was strongly stained at the reactive astrogliosis surrounding the lesions. Myelin basic protein (MBP)-stained myelinated fibers were relatively preserved in the lesions where AQP4 was lost. In contrast to these NMO lesions, AQP4 was expressed predominantly in the gray matter in control spinal cords, and AQP4 was preserved in demyelinating MS lesions. Our findings suggest that astrocytic impairment associated with humoral immunity against AQP4 may be primarily involved in the lesion formation of NMO, and that the pathomechanisms of NMO are different from those of MS in which demyelination is the primary pathology. neuromyelitis optica; opticspinal multiple sclerosis; aquaporin 4; demyelination; astroglia

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Section: Discussionsupporting

confidence: 62%

Loss of Aquaporin-4 in Active Perivascular Lesions in Neuromyelitis Optica: A Case Report

Misu

Fujihara

Nakamura

et al. 2006

Tohoku J. Exp. Med.

110

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“…This occurs in several experimental animal models of demyelination as well as in human demyelinating disease (Snyder et al 1975;Itoyama et al 1983Itoyama et al , 1985Dusart et al 1992;Felts et al 2005). Schwann cell remyelination occurs preferentially where astrocytes are absent, for example, where they have been killed along with oligodendrocytes by the demyelinating agent (Blakemore 1975;Itoyama et al 1985). Remyelinating Schwann cells within the CNS were generally thought to migrate into the CNS from PNS sources, such as spinal and cranial roots, meningeal fibers, or autonomic nerves following a breach in the glia limitans (Franklin and Blakemore 1993).…”

Section: Demyelinated Cns Axons Can Also Be Remyelinated By Schwann Cmentioning

confidence: 99%

Glia Disease and Repair—Remyelination

Franklin

Goldman

2015

Cold Spring Harb Perspect Biol

190

168

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The inability of the mammalian central nervous system (CNS) to undergo spontaneous regeneration has long been regarded as a central tenet of neurobiology. However, although this is largely true of the neuronal elements of the adult mammalian CNS, save for discrete populations of granular neurons, the same is not true of its glial elements. In particular, the loss of oligodendrocytes, which results in demyelination, triggers a spontaneous and often highly efficient regenerative response, remyelination, in which new oligodendrocytes are generated and myelin sheaths are restored to denuded axons. Yet, remyelination in humans is not without limitation, and a variety of demyelinating conditions are associated with sustained and disabling myelin loss. In this review, we will review the biology of remyelination, including the cells and signals involved; describe when remyelination occurs and when and why it fails and the consequences of its failure; and discuss approaches for therapeutically enhancing remyelination in demyelinating diseases of both children and adults, both by stimulating endogenous oligodendrocyte progenitor cells and by transplanting these cells into demyelinated brain. IDENTIFYING REMYELINATIONR emyelination is the process in which new myelin sheaths are restored to axons that have lost their myelin sheaths as a result of primary demyelination. Primary demyelination is the term used to describe the loss of myelin from an otherwise intact axon and should be distinguished from myelin loss secondary to axonal loss-a process called Wallerian degeneration or, misleadingly, secondary demyelination. Remyelination is sometimes referred to as myelin repair. However, this term suggests a damaged but otherwise intact myelin internode being "patched up," a process for which there is no evidence and which does not emphasize the truly regenerative nature of remyelination, in which the prelesion cytoarchitecture is substantially restored. Remyelinated tissue very closely resembles normally myelinated tissue but differs in one important aspect-the newly generated myelin sheaths are typically shorter and thinner than the original myelin sheaths. When myelin is initially formed in the peri-and postnatal period, there is a striking correlation between axon diameter and myelin sheath thickness and length, which is less apparent in remyelination. Instead, myelin sheath thickness and

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“…Since Schwann cell and oligodendrocyte remyelination in the CNS is a well-known event in demyelinating diseases such as multiple sclerosis (15)(16)(17) as well as in the EB gliotoxic model, the aim of the present investigation was to determine the behavior of these myelin-repairing cells after local EB injection in the brainstem of rats submitted to the diabetogenic model of streptozotocin.…”

Section: Introductionmentioning

confidence: 99%

Delayed Schwann cell and oligodendrocyte remyelination after ethidium bromide injection in the brainstem of Wistar rats submitted to streptozotocin diabetogenic treatment

Bondan

Lallo

Trigueiro

et al. 2006

Braz J Med Biol Res

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Schwann cell disturbance followed by segmental demyelination in the peripheral nervous system occurs in diabetic patients. Since Schwann cell and oligodendrocyte remyelination in the central nervous system is a well-known event in the ethidium bromide (EB) demyelinating model, the aim of this investigation was to determine the behavior of both cell types after local EB injection into the brainstem of streptozotocin diabetic rats. Adult male Wistar rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 µL 0.1% (w/v) EB or 0.9% saline solution into the cisterna pontis. Ten microliters of 0.1% EB was also injected into non-diabetic rats. The animals were anesthetized and perfused through the heart 7 to 31 days after EB or saline injection and brainstem sections were collected and processed for light and transmission electron microscopy. The final balance of myelin repair in diabetic and non-diabetic rats at 31 days was compared using a semiquantitative method. Diabetic rats presented delayed macrophage activity and lesser remyelination compared to non-diabetic rats. Although oligodendrocytes were the major remyelinating cells in the brainstem, Schwann cells invaded EB-induced lesions, first appearing at 11 days in non-diabetic rats and by 15 days in diabetic rats. Results indicate that short-term streptozotocin-induced diabetes hindered both oligodendrocyte and Schwann cell remyelination (mean remyelination scores of 2.57 ± 0.77 for oligodendrocytes and 0.67 ± 0.5 for Schwann cells) compared to non-diabetic rats (3.27 ± 0.85 and 1.38 ± 0.81, respectively).

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Spinal cord multiple sclerosis lesions in Japanese patients: Schwann cell remyelination occurs in areas that lack glial fibrillary acidic protein (GFAP)

Cited by 70 publications

References 33 publications

Loss of Aquaporin-4 in Active Perivascular Lesions in Neuromyelitis Optica: A Case Report

Loss of Aquaporin-4 in Active Perivascular Lesions in Neuromyelitis Optica: A Case Report

Glia Disease and Repair—Remyelination

Delayed Schwann cell and oligodendrocyte remyelination after ethidium bromide injection in the brainstem of Wistar rats submitted to streptozotocin diabetogenic treatment

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