Schwann cell expression of an oligodendrocyte-like remyelinating pattern after ethidium bromide injection in the rat spinal cord (original) (raw)
Related papers
Journal of Neurocytology, 1988
Transplantation of oligodendrocytes or Schwann cells into the spinal cord of the newborn myelin-deficient (md) rat, an X-linked myelin mutant, was carried out and the extent of myelination of CNS axons studied. Dissociated glial cell suspensions, prepared from the spinal cords of female litter-mates, were injected into the lumbar spinal cord of 15 md rats and 5 normal litter-mates. In eight of the md rats examined 12 to 21 days post-transplantation patches of myelin produced by the transplanted oligodendrocytes were found in the dorsal or ventral columns. In two rats, small patches of myelination were found in more than one site. The myelin in these patches was positive on immunocytochemical staining for proteolipid protein. These observations were interpreted as evidence of the origin of this myelin from donor oligodendrocytes, as the md rat has an abnormality in synthesis of this protein. In addition, this myelin differed in its ultrastructure from host myelin, having a normal intraperiod line. Injection of cultured Schwann ceils also resulted in extensive myelination of axons in the dorsal columns by these cells.
Pattern of schwann cell remyelination in a spinal cord lesion
Neuroscience Letters, 1984
Intraspinal injection of mitomycin C into the rat dorsal columns produced extensive demyelination, axonal degeneration and glial cell death. Five weeks post-injection Schwann cell remyelinated fibers were present along the surface of the dorsal columns and around blood vessels within the lesions. Axons near these sites either were enclosed within a Schwann cell but not myelinated or were completely devoid of any cellular ensheathment. Schwann cells were associated only with those blood vessels which no longer retained astroglial end-feet. It is concluded that Schwann cells migrate into spinal cord lesions along such vessels. The marked sub-pial and perivascular distribution of Schwann cell remyelinated fibers may reflect a failure of Schwann cells to disperse quickly elsewhere within the lesion.
Experimental Neurology, 1998
We previously observed that the transient developmental suppression of myelination or disruption of mature myelin, by local intraspinal infusion of serum complement proteins along with a complement-fixing, myelin-specific antibody (e.g., anti-Galactocerebroside), facilitated avian brainstem-spinal axonal regeneration after spinal transection. We now report the effects of similar immunological protocols on axonal regeneration in the injured adult rat spinal cord. After a lateral hemisection injury of the T10 spinal cord, infusion of the above reagents, over 14 days at T11, facilitated the regeneration of some brainstem-spinal axons. The hemisection lesion enabled comparisons between the retrograde labeling within an injured brainstem-spinal nucleus and the uninjured contralateral homologue. The brainstem-spinal nucleus examined in detail was the red nucleus (RN), chosen for its relatively compact descending pathway within the dorsolateral cord. Comparing the number of labeled neurons within each RN, of an experimentally myelin suppressed animal, indicated that approximately 32% of injured rubrospinal projections had regenerated into the caudal lumbar cord. In contrast, controltreated animals (e.g., PBS vehicle alone, GalC antibody alone, or serum complement alone) showed little or no axonal regeneration. We also examined the ultrastructural appearance of the treated cords. We noted demyelination over 1-2 segments surrounding the infusion site (T11) and a further two segments of myelin disruption (delamination) on either side of the demyelinated zone. The demyelination is an active process (F3 days) with microglia and/or macrophages engulfing myelin. Thus, the facilitation of axonal regeneration through the transient suppression of CNS myelin may be fundamental to all higher vertebrates. 1998 Academic Press
Neuroscience Letters, 1988
Fragments of normal newborn mouse central nervous system (CNS) were transplanted into the spinal cord of adult shiverer mice at distance of 1, 2 or 3 intervertebral spaces from a lysolecithin-induced demyelinating lesion. Remyelination by grafted oligodendrocytes was observed by electron microscopy (EM). This result showed the capability of grafted oligodendrocytes or precursor cells to migrate to a demyelinated lesion and to remyelinate naked axons in an adult host, even in presence of host spontaneous remyelination.
Experimental Neurology, 2008
Stem cell therapy is a promising approach for remyelination strategies in demyelinating and traumatic disorders of the spinal cord. Self-renewing neural stem/progenitor cells (NSPCs) reside in the adult mammalian brain and spinal cord. We transplanted NSPCs derived from the adult spinal cord of transgenic rats into two models of focal demyelination and congenital dysmyelination. Focal demyelination was induced by X-irradiation and ethidium bromide injection (X-EB); and dysmyelination was in adult shiverer mutant mice, which lack compact CNS myelin. We examined the differentiation potential and myelinogenic capacity of NSPCs transplanted into the spinal cord. In X-EB lesions, the transplanted cells primarily differentiated along an oligodendrocyte lineage but only some of the oligodendrocytic progeny remyelinated host axons. In this glial-free lesion, NSPCs also differentiated into cells with Schwann-like features based on ultrastructure, expression of Schwann cell markers, and generation of peripheral myelin. In contrast, after transplantation into the spinal cord of adult shiverer mice, the majority of the NSPCs expressed an oligodendrocytic phenotype which myelinated the dysmyelinated CNS axons forming compact myelin, and none had Schwann cell-like features. This is the first study to examine the differentiation and myelinogenic capacity of adult spinal cord stem/progenitors in focal demyelination and dysmyelination of the adult rodent spinal cord. Our findings demonstrate that these NSPCs have the inherent plasticity to differentiate into oligodendrocytes or Schwann-like cells depending on the host environment, and that both cell types are capable of myelinating axons in the demyelinated and dysmyelinated adult spinal cord.
Efficient myelin repair in the macaque spinal cord by autologous grafts of Schwann cells
Brain, 2005
Experimental transplantation in rodent models of CNS demyelination has led to the idea that Schwann cells may be candidates for cell therapy in human myelin diseases. Here we investigated the ability of Schwann cells autografts to generate myelin in the demyelinated monkey spinal cord. We report that monkey Schwann cells derived from adult peripheral nerve biopsies retain, after growth factor expansion and transduction with a lentiviral vector encoding green fluorescent protein, the ability to differentiate in vitro into promyelinating cells. When transplanted in the demyelinated nude mouse spinal cord, they promoted functional and anatomical repair of the lesions (n = 12). Furthermore, we obtained evidence by immunohistochemistry (n = 2) and electron microscopy (n = 4) that autologous transplantation of expanded monkey Schwann cells in acute lesions of the monkey spinal cord results in the repair of large areas of demyelination; up to 55% of the axons were remyelinated by donor Schwann cells, the remaining ones being remyelinated by oligodendrocytes. Autologous grafts of Schwann cells may thus be of therapeutic value for myelin repair in the adult CNS.
Studies of the Initiation of Myelination by Schwann Cells
Annals of The New York Academy of Sciences, 1990
The myelin sheath contains a number of well-known proteins and lipids that are found only, or are greatly enriched, in myelin. A concentrated research effort over the past decade has laid a foundation for an understanding of how these components of the myelin membrane are made, delivered, and organized into the mature, compacted sheath. Much less is known about the mechanism by which the process of myelination is initiated and about its dependence on molecules not present in or not specific for myelin membranes. The molecules that mediate the recognition and engulfment of myelinatable axons have not been identified; neither have those hypothetical molecules that induce or up-regulate the synthesis of myelin components. In addition, the cytoplasmic and cytoskeletal dynamics that must underlie the growth of the myelin spiral are poorly understood.
Myelin-axon relationships established by rat vagal Schwann cells deep to the brainstem surface
The Journal of Comparative Neurology, 1991
The central-peripheral transitional zones of rat dorsolateral vagal rootlets are highly complex. Peripheral nervous tissue extends centrally for up to several hundred micrometers deep to the brainstem surface along these rootlets. In some instances this peripheral nervous tissue lacks continuity with the peripheral nervous system (PNS) and so forms an island within the central nervous system (CNS). In conformity with the resulting complexity of the CNS-PNS interface, segments of vagal axons lying deep to the brainstem surface are myelinated by one or more intercalated Schwann cells, contained in peripheral tissue insertions or islands, at either end of which they traverse an astroglial barrier. Intercalated Schwann cells are thus isolated from contact or contiguity with the Schwann cells of the PNS generally. They are short, having a mean internodal length of around 60% of that of the most proximal Schwann cells of the PNS proper, which lie immediately distal to the CNS-PNS interface and which are termed transitional Schwann cells. The thickness of the myelin sheaths produced by intercalated Schwann cells is intermediate between that of transitional Schwann cells and that of oligodendrocytes myelinating vagal axons of the same calibre distribution. This is not due to limited blood supply or to insufficient numbers of intercalated Schwann cells, the density of which is greater than that of transitional Schwann cells. These factors are unlikely to restrict expression of their myelinogenic potential. Nevertheless, the regression data show that the setting of the myelin-axon relationship differs significantly between the two categories of Schwann cell. Thus, the myelinogenic response of Schwann cells to stimuli emanating from the same axons may differ between levels along one and the same nerve bundle. Mean myelin periodicity was found to differ between sheaths produced by intercalated and by transitional Schwann cells.