Basic fibroblast growth factor (bFGF) injection activates the glial reaction in the injured adult rat brain

Eclancher, Françoise; Kehrli, P.; Labourdette, G.; Sensenbrenner, M.

doi:10.1016/0006-8993(96)00732-9

Cited by 92 publications

(50 citation statements)

References 70 publications

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“…The fact that inhibitors of these enzymes are able to block the FGF-2-induced response shows that conventional triggering pathways regulate CHL1 expression. Not only in vitro, but also in vivo, when injected into the unlesioned spinal cord, FGF-2 enhanced the expression of CHL1 in parallel with a previously described enhancement of GFAP expression (Lewis et al, 1992;Eclancher et al, 1996;Liu et al, 2005). In addition, in vitro assays confirmed that FGF-2 influences CHL1-associated migration and proliferation of astrocytes as indicated by its more potent effects on CHL1 ϩ/ϩ astrocytes than on CHL1 Ϫ/Ϫ astrocytes.…”

Section: Enhanced Functional Recovery In Chl1-deficient Micesupporting

confidence: 58%

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

Jakovčevski

Wu²,

Karl³

et al. 2007

J. Neurosci.

113

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The Ig superfamily adhesion molecule CHL1, the close homolog of the adhesion molecule L1, promotes neurite outgrowth, neuronal migration, and survival in vitro. We tested whether CHL1, similar to its close homolog L1, has a beneficial impact on recovery from spinal cord injury using adult CHL1-deficient (CHL1 Ϫ/Ϫ ) mice and wild-type (CHL1 ϩ/ϩ ) littermates. In contrast to our hypothesis, we found that functional recovery, assessed by locomotor rating and video-based motion analyses, was improved in CHL1 Ϫ/Ϫ mice compared with wild-type mice at 3-6 weeks after compression of the thoracic spinal cord. Better function was associated with enhanced monoaminergic reinnervation of the lumbar spinal cord and altered pattern of posttraumatic synaptic rearrangements around motoneurons. Restricted recovery of wild-type mice was likely related to early and persistent (3-56 d after lesion) upregulation of CHL1 in GFAP-positive astrocytes at the lesion core. In both the intact spinal cord and cultured astrocytes, enhanced expression of CHL1 and GFAP was induced by application of basic fibroblast growth factor, a cytokine involved in the pathophysiology of spinal cord injury. This upregulation was abolished by inhibitors of FGF receptor-dependent extracellular signal-regulated kinase, calcium/calmodulin-dependent kinase, and phosphoinositide-3 kinase signaling pathways. In homogenotypic and heterogenotypic cocultures of neurons and astrocytes, reduced neurite outgrowth was observed only if CHL1 was simultaneously present on both cell types. These findings and novel in vitro evidence for a homophilic CHL1-CHL1 interaction indicate that CHL1 is a glial scar component that restricts posttraumatic axonal growth and remodeling of spinal circuits by homophilic binding mechanisms.

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Section: Enhanced Functional Recovery In Chl1-deficient Micesupporting

confidence: 58%

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

Jakovčevski

Wu²,

Karl³

et al. 2007

J. Neurosci.

113

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“…It activates the glial reaction in the injured brain, thus influencing the regulation of ECM components in the brain inflammatory process (20,21) In the central nervous system, FGF is found in the cytoplasm and nucleus of neurons and astrocytes (22,23) and exerts its biological action through the binding with FGF receptors (FGFRs), identified as low-and high-affinity receptors (24). FGF2 was shown to be elevated in Alzheimer's disease and localized in the plaques and neurofibrillary tangles (25).…”

Section: Differences In Extracellular Matrix Production and Basic Fibmentioning

confidence: 99%

Differences in Extracellular Matrix Production and Basic Fibroblast Growth Factor Response in Skin Fibroblasts from Sporadic and Familial Alzheimer’s Disease

Bellucci

Lilli

Baroni

et al. 2007

Mol Med

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Extracellular matrix (ECM) molecules and growth factors, such as fibroblast growth factor (FGF), play a crucial role in Alzheimer's disease (AD). The purpose of this investigation was to determine whether phenotypic alterations in ECM production are present in non-neuronal AD cells associated with different FGF expression and response. Synthesis of glycosaminoglycans (GAG) and collagen were measured in skin fibroblasts from patients with familial, sporadic AD (FAD and SAD respectively), and from agematched controls by radiolabeled precursors. Proteoglycans (PG), metalloprotease (MMP)-1, and FGF gene expressions were measured by reverse transcription-polymerase chain reaction. The results showed different ECM neosynthesis and mRNA levels in the two AD fibroblast populations. FAD accumulated more collagen and secreted less GAG than SAD. Biglycan PG was upregulated in FAD while betaglycan, syndecan, and decorin were markedly downregulated in SAD fibroblasts. We found a significant decrease of MMP1, more marked in FAD than in SAD fibroblasts. Constitutive FGF expression was greatly reduced in both pathological conditions (SAD > FAD). Moreover, an inverse high affinity/low affinity FGF receptor ratio between SAD and FAD fibroblasts was observed. FGF treatment differently modulated ECM molecule production and gene expression in the two cell populations. These observations in association with the changes in FGF gene expression and in the FGF receptor number, suggest that cellular mechanisms downstream from FGF receptor binding are involved in the two different forms of AD.

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“…Additionally, nucleotides activate microglia P2 receptors which induce chemotaxis [12,13], phagocytosis [14], the release of trophic factors [15] and cytokines [16] that may have protective effects in cerebral injury [17,18]. Several cytokines and growth factors released by microglia, such as interleukin-1β, interleukin-6, interferon-γ, tumour necrosis factor-α and fibroblast growth factor-2 stimulate astrogliosis [19][20][21] whereas others, such as interleukin-10, attenuate astroglial reactivity through a decrease in microglia activation [22,23]. Furthermore, the in vitro and in vivo demonstration that microglia activation precedes astrogliosis lead to the proposal that these cells are of major relevance in the modulation of this response [24].…”

Section: Introductionmentioning

confidence: 99%

P2Y receptors on astrocytes and microglia mediate opposite effects in astroglial proliferation

Quintas

Fraga

Gonçalves

et al. 2011

Purinergic Signalling

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Nucleotides released upon brain injury signal to astrocytes and microglia playing an important role in astrogliosis, but the participation of microglia in the purinergic modulation of astrogliosis is still unclear. Highly enriched astroglial cultures and co-cultures of astrocytes and microglia were used to investigate the influence of microglia in the modulation of astroglial proliferation mediated by nucleotides. In highly enriched astroglial cultures, adenosine-5'-triphosphate (ATP), adenosine 5'-O-(3-thio)-triphosphate (ATPγS), adenosine 5'-O-(3-thio)-diphosphate (ADPβS; 0.01-1 mM), and adenosine-5'-diphosphate (ADP; 0.1-1 mM) increased proliferation up to 382%, an effect abolished in co-cultures containing 8% of microglia. The loss of ATP proliferative effect in co-cultures is supported by its fast metabolism and reduced ADP accumulation, an agonist of P2Y 1,12 receptors that mediate astroglial proliferation. No differences in ADPβS and ATPγS metabolism or P2Y 1,12 receptors expression were found in co-cultures that could explain the loss of their proliferative effect. However, conditioned medium from microglia cultures or co-cultures treated with ADPβS, when tested in highly enriched astroglial cultures, also prevented ADPβS proliferative effect. None of the uracil nucleotides tested had any effect in proliferation of highly enriched astroglial cultures, but uridine-5′-triphosphate (UTP; 0.1-1 mM) inhibited proliferation up to 66% in co-cultures, an effect that was dependent on uridine-5'-diphosphate (UDP) accumulation, coincident with a co-localization of P2Y 6 receptors in microglia and due to cell apoptosis. The results indicate that microglia control astroglial proliferation by preventing the proliferative response to adenine nucleotides and favouring an inhibitory effect of UTP/UDP. Several microglial P2Y receptors may be involved by inducing the release of messengers that restrain astrogliosis, a beneficial effect for neuronal repair mechanisms following brain injury.

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Basic fibroblast growth factor (bFGF) injection activates the glial reaction in the injured adult rat brain

Cited by 92 publications

References 70 publications

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

Differences in Extracellular Matrix Production and Basic Fibroblast Growth Factor Response in Skin Fibroblasts from Sporadic and Familial Alzheimer’s Disease

P2Y receptors on astrocytes and microglia mediate opposite effects in astroglial proliferation

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