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W F Blakemore

Publications and source records attributed to W F Blakemore.

At least 91 records · Page 5Linked to original sources
PubMed1993

Failure of remyelination in areas of demyelination produced in the spinal cord of old rats.

The extent of remyelination was determined one month after injecting 1 microliter of 1.0% lysolecithin into the dorsal columns of adult rats of three age groups--juvenile, young and old. In the juvenile group (2 months) all axons were remyelinated by either oligodendrocytes or Schwann cells. In the young rats (5 months) nearly all axons were remyelinated. However, in the oldest age group (> 12 months) many axons remained demyelinated and there was a decrease in both oligodendrocyte and Schwann cell remyelination. Also, myelin sheaths formed by oligodendrocytes in the old rats were thinner than those found in the young rats; evidence of impaired Schwann cell remyelination was also seen. The appearance of the lesions in the old animals was variable and many contained myelin debris despite the presence of macrophages within the demyelination area. Although some astrocytes were present in the lesion, many of the demyelinated axons were not separated by astrocyte processes. It is suggested that the failure of remyelination in the old rats following lysolecithin-induced demyelination may be related to sluggish responses of astrocytes and/or macrophages to demyelination. However, a lack of recruitable myelin-forming cells in old animals cannot be excluded.

Aging↗
PubMed1992

The differentiation of glial cell progenitor populations following transplantation into non-repairing central nervous system glial lesions in adult animals.

The non-repairing nature of the locally x-irradiated ethidium bromide (EB)-induced demyelinating white matter lesion has been further validated by showing that injections of two cultures which promote host remyelination of EB lesions in normal tissue do not do so in x-irradiated lesions. The behaviour of an oncogene-immortalized glial cell line and a growth-factor-expanded glial progenitor population have been examined following transplantation into the non-repairing EB lesion. Our studies indicate that the selected glial cell populations were each capable of establishing glial environments around demyelinated axons. Extensive oligodendrocyte remyelination with little astrocytic presence was observed in lesions transplanted with growth-factor-expanded optic nerve progenitors, while less extensive oligodendrocyte remyelination with the establishment of astrocyte-like cells was found in lesions transplanted with ts A58-SV40T immortalized glial cells. Prolonged expansion of both populations resulted in a loss of differentiation to normal glial phenotypes.

Animals↗
PubMed1992

The behaviour of meningeal cells following glial cell transplantation into chemically-induced areas of demyelination in the CNS.

Following transplantation of cultures of CNS glia containing leptomeningeal cells into ethidium bromide-induced demyelinating lesions, meningeal cells adopt either compacted or diffuse arrangements. The compacted arrangements involved no interactions with other cellular components of the remyelinating environment, and were particularly prominent following transplantation of cultures containing a high proportion of fibronectin-positive meningeal cells. The diffuse arrangements involved interactions with astrocytes, Schwann cells and endothelial cells, and contributed to a fragmented appearance of the lesion. Such observations indicate that meningeal cell contamination should be avoided when attempts are being made to repopulate glial-deficient lesions in the CNS by transplanting central glial cells, since their effect is to partition the glial environment.

Animals↗
PubMed1992

Transplanted cultured type-1 astrocytes can be used to reconstitute the glia limitans of the CNS: the structure which prevents Schwann cells from myelinating CNS axons.

Transplantation of different glial cells into areas of demyelination made in the adult rat spinal cord allows insights into the cell-cell interaction necessary to reconstruct a glial environment around demyelinated axons. Such studies have shown that type-1 astrocytes are central to the exclusion of Schwann cells from areas of glia-free demyelination. However, for these cells to be established in a manner which prevents Schwann cell remyelination of CNS axons, cells of the O-2A lineage are also required. If cultures of isogeneic rat type-1 astrocytes and mouse O-2A cells are transplanted into lesions made in non-immunosuppressed animals. Schwann cell remyelination is limited and extensive oligodendrocyte remyelination is achieved. This paradigm creates a model of immune mediated demyelination in which the immune response is not primarily directed at oligodendrocyte specific epitopes.

Animals↗
PubMed1992

Type 1 astrocytes fail to inhibit Schwann cell remyelination of CNS axons in the absence of cells of the O-2A lineage.

The extent to which Schwann cells are able to remyelinate demyelinated CNS axons is influenced by the presence of astrocytes. In order to study further the nature of astrocyte control of Schwann cell remyelination in the CNS, cultures containing type 1 astrocytes and a small proportion of Schwann cells, but depleted of O-2A lineage cells by exposure to cytosine arabinoside and complement-mediated immunocytolysis, were transplanted into glial-free lesions in adult rat spinal cord in which the host response to demyelinated axons was suppressed by X-irradiation. Following transplantation of these O-2A lineage-depleted cultures into X-irradiated, demyelinating lesions, there was extensive remyelination of demyelinated axons by Schwann cells, a result which contrasted with those obtained from earlier experiments in which O-2A lineage cells were present within the transplant, and/or recruited from host tissue. This experiment shows that the presence of O-2A lineage cells is required in order for transplanted type 1 astrocytes to organise in a manner which inhibits extensive Schwann cell remyelination of CNS axons.

Animals↗
PubMed1991

Remyelination of demyelinated rat axons by transplanted mouse oligodendrocytes.

The injection of the gliotoxic agent ethidium bromide (EB) into spinal white matter produces a CNS lesion in which it is possible to investigate the ability of transplanted glial cells to reconstruct a glial environment around demyelinated axons. This study demonstrates that transplanted mouse glial cells can repopulate EB lesions in rats provided tissue rejection is controlled. In X-irradiated EB lesions in cyclosporin-A-treated rats, mouse oligodendrocytes remyelinated rat axons and, together with mouse astrocytes, re-established a CNS environment. When transplanted into nonirradiated EB lesions in nude rats, mouse glial cells modulated the normal host repair by Schwann cells to remyelination by oligodendrocytes. In both X-irradiated and non-irradiated EB lesions, transplanted mouse glial cells behaved similarly to isogenic rat glial cell transplants (Blakemore and Crang Dev Neurosci, 1988;10:1-10; J Neurocytol, 1989;18:519-528). These findings indicate that the cell-cell interactions involved in reconstruction of a glial environment are common to both mouse and rat.

Animals↗
PubMed1991

Transplanted type-1 astrocytes facilitate repair of demyelinating lesions by host oligodendrocytes in adult rat spinal cord.

The ethidium bromide model of demyelination/remyelination provides a system for studying the interactions between demyelinated axons, host glia and transplanted glia. The injection of 0.1% ethidium bromide in isotonic saline into the white matter of the spinal cord produces a glia-free demyelinating lesion which is subsequently remyelinated by Schwann cells and, to a lesser extent, oligodendrocytes. the in vitro description of an oligodendrocyte progenitor isolated from the adult CNS, together with the recognized role of type-1 astroctyes in controlling the developmental programme of perinatal O-2A progenitors, suggested the possibility that transplanted type-1 astrocytes may potentiate oligodendrocyte remyelination of the ethidium bromide lesion. Purified type-1 astrocyte cultures were prepared by removing cells of the oligodendrocyte lineage using a combination of exposure to cytosine arabinoside and complement-mediated immunocytolysis. Following transplantation of purified type-1 astrocyte cultures into ethidium bromide lesions, a significant increase in the extent of oligodendrocyte remyelination was achieved. Because the purified type-1 astrocyte cultures had no demonstrable oligodendrocyte-generating potential it was concluded that the additional oligodendrocytes appearing in the type-1 astrocytes transplanted lesion were of host origin. These results indicate that type-1 astrocytes can facilitate repair of demyelinating lesions by host oligodendrocytes. The possible mechanisms whereby this facilitation occurs are discussed.

Animals↗
PubMed1991

Transplantation of glial cells into the CNS.

Glial cell transplantation into the CNS offers an experimental approach to help us unravel the complex interactions that occur between CNS glia, Schwann cells and axons during repair and development. This article reviews recent advances that have been made in our understanding of the nature and potential of CNS repair using this approach, and introduces the idea of using transplantation to address broader issues in glial biology.

Animals↗
PubMed1991

A primary demyelinating disorder of young cattle.

The clinical signs and neuropathological changes are described in six Limousin X calves that, at about one month after birth, showed signs of blindness, nystagmus, rotation of the eyes, opisthotonos, hyperprotraction of the forelegs and, in one case, apparent seizures. Pathologically there was necrosis of the optic chiasma and focal areas of myelin sheath vacuolation or demyelination in certain areas of the brain, especially in the cerebellar peduncles. In one animal, kept alive for 7 months, there was remyelination by Schwann cells of some demyelinated axons in the focal cerebellar lesions, while other axons remained demyelinated. There was no evidence of oligodendrocyte remyelination. The cause of the condition was not determined but a genetic association is likely.

Age Factors↗
PubMed1990

Ultrastructural findings in spongy degeneration of white matter in silver foxes (Vulpes vulpes). A naturally occurring demyelinating disease with oligodendrocyte vacuolation.

Spongy degeneration of white matter in silver foxes is a naturally occurring, hereditary disorder. We report ultrastructural findings in the upper cervical cord of five perfusion-fixed foxes that were examined between 5 weeks and 2 1/4 years after the onset of clinical signs. Large cytoplasmic vacuoles in oligodendrocytes were present in the foxes examined 5, 12 and 20 weeks after the onset. Other early features of the disease were severe vacuolation of myelin sheaths, demyelination, expansion of extracellular spaces and hypertrophy of astrocytes. Evidence of partial demyelination as well as demyelination of entire internodes was found. In the later stages of the disease, the vacuolation was largely resolved but a marked astrogliosis persisted and numerous remyelinated axons were present in the gliotic areas. Vacuolation of oligodendrocytes and partial demyelination has not previously been seen together in a single disease process. The relationship between oligodendrocyte vacuolation, myelin sheath vacuolation and demyelination is discussed. It is concluded that the present condition is due to a primary damage to oligodendrocytes; however, the underlying biochemical lesion is not known.

Animals↗
PubMed1990

Pathogenesis of meningitis caused by Streptococcus suis type 2.

The neuraxes of 26 pigs inoculated intravenously with a pathogenic isolate of Streptococcus suis type 2 and killed 17-47 h later were examined using histologic and scanning microscopic techniques. The only pathologic lesions detected in all pigs were associated with the choroid plexus: disruption of the plexus brush border, a decrease in the number of Kolmer cells, and exudation of fibrin and inflammatory cells into the ventricles. Lesions affecting the cerebral and choroid plexus endothelium, such as vasculitis, were not detected. Intracellular bacteria were demonstrated in the parenchyma of the choroid plexus, in the ventricular exudate, and within peripheral blood monocytes. Separate studies found that circulating monocytes containing phagocytosed bacteria-sized particles migrated into the cerebrospinal fluid compartment with the choroid plexus acting as a major site of cellular ingress. These observations support the concept that in the pathogenesis of meningitis, bacteria may gain access to the cerebrospinal fluid compartment in association with monocytes migrating along normal pathways.

Animals↗
PubMed1990

Pathology of Streptococcal meningitis following intravenous intracisternal and natural routes of infection.

The distribution of pathological lesions present in 20 cases of naturally-occurring Streptococcus suis type 2 meningitis and 20 cases of the disease induced experimentally by intravenous or intracisternal inoculation was examined. It was found that the distribution of lesions was similar; mild lesions were present at the choroid plexuses whilst the most dense cellular accumulations were found at sites of cerebrospinal fluid (CSF) efflux, such as arachnoid villi and olfactory nerve sheaths. The distribution of changes was considered to reflect the dynamics of CSF flow rather than indicate the site of entry of the organisms into the CSF compartment.

Animals↗
PubMed1990

Monocyte-mediated entry of pathogens into the central nervous system.

The origin of the microglia has long been a subject of debate. However it is now clear that monocytes enter the normal central nervous system and follow a series of morphological transformations as they differentiate into microglia. Thus, microglia are of monocytic origin. Since monocytes migrate into the normal CNS, they represent potential vehicles for the entry of pathogens into the nervous system and indeed may carry particulate matter into the CNS. Both viruses and bacteria use this 'Trojan horse' mechanism of entry in the pathogenesis of CNS disease.

Animals↗
PubMed1989

The effect of the number of oligodendrocytes transplanted into X-irradiated, glial-free lesions on the extent of oligodendrocyte remyelination.

Central nervous system mixed glia cell cultures were prepared which contained varying proportions of galactocerebroside-positive oligodendrocytes and high proportions of GFAP-positive flat astrocytes. When these cell preparations were transplanted into areas of persistent demyelination produced in the dorsal columns of adult rat spinal cord, it was found that the number of oligodendrocyte internodes formed and the extent of CNS reconstruction achieved was directly related to the number of oligodendrocytes introduced to the lesioned area. With transplants containing low numbers of oligodendrocytes, astrocytes appeared unable to establish relationships within the lesioned areas and only Schwann cells, which comprise less than 5% of the total cell preparation, effected significant remyelination. These results indicate that a minimum number of oligodendrocytes are required to support significant reconstruction of CNS territories in the face of competition-for-axons from contaminating Schwann cells.

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