CNTF regulation of astrogliosis and the activation of microglia in the developing rat central nervous system

Kahn, M.A.; Ellison, Julie A.; Speight, Graham; Vellis, Jean de

doi:10.1016/0006-8993(95)00411-i

Cited by 107 publications

(51 citation statements)

References 59 publications

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“…41,61 The effect of CNTF on spinal cord inflammation is unlikely to be linked to a direct effect of this cytokine on T cells because these cells are neither known to express CNTFR␣ nor LIFR␤. 13,65,66 It is conceivable that CNTF exerts its effects on the spinal cord immune response via immune modulating molecules produced by microglia, a cell population known to respond to CNTF 67,68 or a direct neuroprotective effect preventing initial myelin and axon damage and therefore blocking secondary inflammatory response. 69 The ability of CNTF to cross the BBB is prerequisite for a direct effect of CNTF on microglial cells or myelin and axons.…”

Section: Discussionmentioning

confidence: 99%

Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

Kuhlmann

Remington

Cognet

et al. 2006

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 99%

Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

Kuhlmann

Remington

Cognet

et al. 2006

The American Journal of Pathology

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“…Degeneration of severed axon tracts appears to lead to gliosis, even in regions remote from the site of trauma in the brain or spinal cord (Barrett et al, 1981;Fitch and Silver, 1997a;Massey, et al, 2006;Murray et al, 1990;Steward and Trimmer, 1997). Cytokines or other molecules that may trigger gliosis include TNF-alpha (Rostworowski et al, 1997), endothelin-1 (Hama et al, 1997), IL-1 (Giulian and Lachman, 1985), IL-6 (Chiang et al, 1994), thrombin (Nishino et al, 1993), and CNTF (Kahn et al, 1995). Some of these may originate as soluble serum factors, or they can be directly produced by astrocytes, activated microglia, or peripheral macrophages.…”

Section: Triggers For the Production Of Inhibitory Extracellular Matrixmentioning

confidence: 99%

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Fitch

Silver

2008

Experimental Neurology

877

657

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Spinal cord and brain injuries lead to complex cellular and molecular interactions within the central nervous system in an attempt to repair the initial tissue damage. Many studies have illustrated the importance of the glial cell response to injury, and the influences of inflammation and wound healing processes on the overall morbidity and permanent disability that result. The abortive attempts of neuronal regeneration after spinal cord injury are influenced by inflammatory cell activation, reactive astrogliosis and the production of both growth promoting and inhibitory extracellular molecules. Despite the historical perspective that the glial scar was a mechanical barrier to regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Unlike myelin associated inhibitory molecules, which remain at largely static levels before and after central nervous system trauma, inhibitory extracellular matrix molecules are dramatically upregulated during the inflammatory stages after injury providing a window of opportunity for the delivery of candidate therapeutic interventions. While high dose methylprednisolone steroid therapy alone has not proved to be the solution to this difficult clinical problem, other strategies for modulating inflammation and changing the make up of inhibitory molecules in the extracellular matrix are providing robust evidence that rehabilitation after spinal cord and brain injury has the potential to significantly change the outcome for what was once thought to be permanent disability.

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“…An increase in CNTF concentra-tion leads to astrocyte hypertrophy and GFAP overexpression in vitro (Levison et al, 1998) and in vivo (Kahn et al, 1995;Winter et al, 1995;Lisovoski et al, 1997). In addition, the levels of endogenous CNTF are increased in conditions associated with astrocytic activation such as mechanical injury (Ip et al, 1993) or excitotoxic lesion (Haas et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

Escartin¹,

Brouillet²,

Gubellini³

et al. 2006

J. Neurosci.

111

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To study the functional role of activated astrocytes in glutamate homeostasis in vivo, we used a model of sustained astrocytic activation in the rat striatum through lentiviral-mediated gene delivery of ciliary neurotrophic factor (CNTF). CNTF-activated astrocytes were hypertrophic, expressed immature intermediate filament proteins and highly glycosylated forms of their glutamate transporters GLAST and GLT-1. CNTF overexpression produced a redistribution of GLAST and GLT-1 into raft functional membrane microdomains, which are important for glutamate uptake. In contrast, CNTF had no detectable effect on the expression of a number of neuronal proteins and on the spontaneous glutamatergic transmission recorded from striatal medium spiny neurons. These results were replicated in vitro by application of recombinant CNTF on a mixed neuron/astrocyte striatal culture. Using microdialysis in the rat striatum, we found that the accumulation of extracellular glutamate induced by quinolinate (QA) was reduced threefold with CNTF. In line with this result, CNTF significantly increased QA-induced [ 18 F]-fluoro-2-deoxyglucose uptake, an indirect index of glutamate uptake by astrocytes. Together, these data demonstrate that CNTF activation of astrocytes in vivo is associated with marked phenotypic and molecular changes leading to a better handling of increased levels of extracellular glutamate. Activated astrocytes may therefore be important prosurvival agents in pathological conditions involving defects in glutamate homeostasis.

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CNTF regulation of astrogliosis and the activation of microglia in the developing rat central nervous system

Cited by 107 publications

References 59 publications

Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

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