Astrocyte transplants alleviate lesion induced memory deficits independently of cholinergic recovery

Bradbury, Elizabeth J.; Kershaw, T. R.; Marchbanks, R. M.; Sinden, John D.

doi:10.1016/0306-4522(94)00540-l

Cited by 36 publications

(24 citation statements)

References 67 publications

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“…In other experiments, a nitrocellulose filter embedded with early postnatal astrocytes and implanted into previously acallosal mice provided a terrain suitable for axons to traverse the cerebral midline to reform a corpus callosum (Silver and Ogawa, 1983;Smith et al, 1986). The implantation of astrocytes into adult rats with CNS lesions has resulted in the recovery of T-maze learning behavior (Kesslak et al, 1986;Bradbury et al, 1995) and an increase in the intensity of neurofilament labeling at the lesion site (Wang et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

et al. 1997

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The relevance of astrogliosis remains controversial, especially with respect to the beneficial or detrimental influence of reactive astrocytes on CNS recovery. This dichotomy can be resolved if the mediators of astrogliosis are identified. We have measured the levels of transcripts encoding inflammatory cytokines in injury systems in which the presence or absence of astrogliosis could be produced selectively. A stab injury to the adult mouse brain using a piece of nitrocellulose (NC) membrane elicited a prompt and marked increase in levels of transcripts for interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α, which are considered to be microglia/macrophage cytokines. The elevations preceded, or occurred concomitantly with, the rise in glial fibrillary acidic protein mRNA, an early manifestation of astrogliosis. In neonatal mice, IL-1 and TNF-α mRNA were elevated to a greater extent by an NC-implant injury, which produced astrogliosis, than after an NC-stab, with minimal astrogliosis. We determined whether endogenous interferon (IFN)-γ could be responsible for the observed increases in IL-1 and TNF-α, because IFN-γ is a potent microglia/macrophage activator, and because its exogenous administration to rodents enhanced astrogliosis after adult or neonatal insults. A lack of requirement for endogenous IFN-γ was demonstrated by three lines of evidence. First, no increase in IFN-γ transcripts could be found at injury. Second, the administration of a neutralizing antibody to IFN-γ did not attenuate astrogliosis. Third, in IFN-γ knockout adult mice, astrogliosis and increases in levels of IL-1α and TNF-α were induced rapidly by injury. The marked elevation of inflammatory cytokines is discussed in the context of astrogliosis and general CNS recovery.

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Section: Discussionmentioning

confidence: 99%

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

et al. 1997

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“…Astrocyte culture was prepared as described elsewhere [4]. Astrocyte suspension was transplanted 7 days after injection of KA into field CA1 of the left hippocampus [3].…”

Section: Methodsmentioning

confidence: 99%

Transplantation of cultured astrocytes attenuates degenerative changes in rats with kainic acid-induced brain damage

Ермакова

Loseva

Hodges³

et al. 2005

Bull Exp Biol Med

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Viability of astrocyte grafts introduced into CA1 pyramidal layer of the left dorsal hippocampus after injection of kainic acid into this brain region and the effects of these grafts on the hippocampus and amygdala were studied on Wistar rats. In rats with astrocyte grafts the degree of destruction in fields CA1-CA2 of the dorsal and ventral hippocampus, fields CA3-CA4 of the ventral hippocampus, and central and basolateral amygdala was lower compared to animals with kainic acid-induced hippocampal damage and control rats; destructions in the dentate fascia were absent. Our results suggest that astrocyte grafts stimulate neurogenesis in the mature brain of recipient rats with kainic acid-induced brain damage.

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“…Transplantation of cell suspensions containing astrocytes and O-2A lineage cells will result in reconstruction of the glia limitans in glia-free areas of demyelination (Blakemore & Crang, 1989;Franklin et al, 1992bFranklin et al, , 1993a and there is evidence that transplanted astrocytes reduce infiltration of meningeal cells following traumatic lesions and also limit the development of reactive astrocytosis (Smith et al, 1986;Smith & Silver, 1988;Wang et al, 1995;). Furthermore, several groups have demonstrated that transplanted astrocytes can promote behavioural recovery from a variety of CNS injuries (Kesslak et al, 1986;Fine et al, 1990;Brfickner & Arendt, 1992;Bradbury et al, 1995), and have ascribed this improvement to the production of trophic support by the transplanted astrocytes.…”

Section: In Addition To Their Homeostatic Role In the Adultmentioning

confidence: 97%

Reconstruction of the glial environment of a photochemically induced lesion in the rat spinal cord by transplantation of mixed glial cells

Olby

Blakemore

1996

J Neurocytol

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It is becoming increasingly apparent that the astrocytic environment is critical to the normal development and functioning of the CNS, and that acute injury to the spinal cord causes destruction of glial cells in addition to neurones and axons. The aims of this study were to assess the viability of reconstructing the astrocytic environment of a cystic spinal cord lesion by transplantation of glial cells and to examine the effect of the transplanted cells on meningeal cell invasion and revascularisation of the lesion and on axonal regeneration. Neonatal rat and kitten mixed glial cells and the CG-4 rat O-2A progenitor cell line were transplanted into a lesion produced in the dorsal funiculus of the rat spinal cord by photochemical infarction. The animals were killed 4 weeks after injury, their cords examined with light and electron microscopy and compared with control animals that were injected with medium alone. Transplantation of all three preparations resulted in increased numbers of astrocytes in the area of Wallerian degeneration cranial to the lesion and within the cyst. Mixed glial cell cultures prepared from neonatal rat forebrain contained cells with in vitro characteristics of type-1 astrocytes, and produced dense clusters of astrocytes that were surrounded by meningeal cells, resulting in a fragmented environment in the cyst. In contrast, glial cell cultures prepared from kitten forebrain and the CG-4 cell line produced cells that filled the cyst with a loose network of fine processes and reduced meningeal cell infiltration of the lesion. The CG-4 cell line significantly increased the density of blood vessels in the centre of the lesion and the number of spared axons present dorsal to the lesion, but none of the preparations significantly increased the number of axons regenerating at the caudal end of the lesion. We conclude that O-2A progenitor-derived astrocytes are more suitable for reconstruction of the glial environment of a cystic lesion in the rat spinal cord than 'type-1 like' astrocytes and would therefore be the cell of choice to engineer to produce factors that promote axonal regeneration.

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Astrocyte transplants alleviate lesion induced memory deficits independently of cholinergic recovery

Cited by 36 publications

References 67 publications

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

Transplantation of cultured astrocytes attenuates degenerative changes in rats with kainic acid-induced brain damage

Reconstruction of the glial environment of a photochemically induced lesion in the rat spinal cord by transplantation of mixed glial cells

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