Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; IN-VITRO ; SURVIVAL ; ENDOTHELIAL GROWTH-FACTOR ; Germany ; IN-VIVO ; MODEL ; MODELS ; PATHWAY ; PATHWAYS ; VITRO ; GENERATION ; VOLUME ; DEATH ; DISEASE ; DISEASES ; DRUG ; DIFFERENTIATION ; LIGAND ; MECHANISM ; RAT ; CELL-SURVIVAL ; CELL-DEATH ; LONG-TERM SURVIVAL ; TRANSIENT GLOBAL-ISCHEMIA ; STEM-CELLS ; CENTRAL-NERVOUS-SYSTEM ; COLONY-STIMULATING FACTOR ; STROKE ; signaling ; ADULT ; FOCAL CEREBRAL-ISCHEMIA ; NEURONS ; cell survival ; CEREBRAL-ISCHEMIA ; NEURAL STEM-CELLS ; cell death ; progenitor ; FUNCTIONAL RECOVERY ; MATURE ; RECOVERY ; NEURONAL DIFFERENTIATION ; HIPPOCAMPAL-NEURONS ; FACTOR G-CSF ; INFARCT ; NEWLY GENERATED NEURONS ; RAT DENTATE GYRUS
    Abstract: G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong antiapoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases
    Type of Publication: Journal article published
    PubMed ID: 16007267
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: 3-KINASE, AKT, APOPTOSIS, ARTERY, BARRIER, Bcl-2, BLOOD, BLOOD-BRAIN, BLOOD-BRAIN-BARRIER, BLOOD-FLO
    Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine responsible for the proliferation, differentiation, and maturation of cells of the myeloid lineage, which was cloned more than 20 years ago. Here we uncovered a novel function of GM-CSF in the central nervous system (CNS). We identified the GM-CSF alpha-receptor as an upregulated gene in a screen for ischemia-induced genes in the cortex. This receptor is broadly expressed on neurons throughout the brain together with its ligand and induced by ischemic insults. In primary cortical neurons and human neuroblastoma cells, GM-CSF counteracts programmed cell death and induces BCL-2 and BCL-XI expression in a dose- and time-dependent manner. Of the signaling pathways studied, GMCSF most prominently induced the PI3K-Akt pathway, and inhibition of Akt strongly decreased antiapoptotic activity. Intravenously given GM-CSF passes the blood-brain barrier, and decreases infarct damage in two different experimental stroke models (middle cerebral artery occlusion (MCAO), and combined common carotid/distal MCA occlusion) concomitant with induction of BCL-XI expression. Thus, GM-CSF acts as a neuroprotective protein in the CNS. This finding is remarkably reminiscent of the recently discovered functionality of two other hematopoietic factors, erythropoietin and granulocyte colony-stimulating factor in the CNS. The identification of a third hematopoietic factor acting as a neurotrophic factor in the CNS suggests a common principle in the functional evolution of these factors. Clinically, GM-CSF now broadens the repertoire of hematopoietic factors available as novel drug candidates for stroke and neurodegenerative diseases
    Type of Publication: Journal article published
    PubMed ID: 17457367
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: brain ; synaptic plasticity ; DENTATE GYRUS ; NEURONS ; NEURAL STEM-CELLS ; depression ; GRANULE CELLS ; ADULT HIPPOCAMPAL NEUROGENESIS ; PATTERN SEPARATION ; WNT MODULATORS
    Abstract: Memory impairment has been associated with age-related decline in adult hippocampal neurogenesis. Although Notch, bone morphogenetic protein, and Wnt signaling pathways are known to regulate multiple aspects of adult neural stem cell function, the molecular basis of declining neurogenesis in the aging hippocampus remains unknown. Here, we show that expression of the Wnt antagonist Dickkopf-1 (Dkk1) increases with age and that its loss enhances neurogenesis in the hippocampus. Neural progenitors with inducible loss of Dkk1 increase their Wnt activity, which leads to enhanced self-renewal and increased generation of immature neurons. This Wnt-expanded progeny subsequently matures into glutamatergic granule neurons with increased dendritic complexity. As a result, mice deficient in Dkk1 exhibit enhanced spatial working memory and memory consolidation and also show improvements in affective behavior. Taken together, our findings show that upregulating Wnt signaling by reducing Dkk1 expression can counteract age-related decrease in neurogenesis and its associated cognitive decline.
    Type of Publication: Journal article published
    PubMed ID: 23395445
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: RECEPTOR ; APOPTOSIS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; Germany ; IN-VIVO ; MODEL ; MODELS ; THERAPY ; VITRO ; VIVO ; DISEASE ; GENE ; DRUG ; DIFFERENTIATION ; MICE ; MRI ; BIOLOGY ; TARGET ; MOUSE ; TRANSGENIC MICE ; FIBER ; INSTABILITY ; LENGTH ; NEURITE OUTGROWTH ; INJURY ; G-CSF ; DEFICIENT MICE ; FOCAL CEREBRAL-ISCHEMIA ; HIPPOCAMPAL ; FUNCTIONAL RECOVERY ; spinal cord injury ; HIPPOCAMPAL-NEURONS ; FACTOR G-CSF ; regeneration ; outcome ; SPINAL-CORD-INJURY ; CORTICOSPINAL TRACT ; hematopoietic growth factor ; MANGANESE-ENHANCED MRI ; MOTOR FUNCTION ; PROMOTES RECOVERY ; RESONANCE-IMAGING MEMRI
    Abstract: P〉Granulocyte-colony stimulating factor (G-CSF) is a potent hematopoietic factor that drives differentiation of neutrophilic granulocytes. We have recently shown that G-CSF also acts as a neuronal growth factor, protects neurons in vitro and in vivo, and has regenerative potential in various neurological disease models. Spinal cord injury (SCI) following trauma or secondary to skeletal instability is a terrible condition with no effective therapies available at present. In this study, we show that the G-CSF receptor is up-regulated upon experimental SCI and that G-CSF improves functional outcome in a partial dissection model of SCI. G-CSF significantly decreases apoptosis in an experimental partial spinal transsection model in the mouse and increases expression of the anti-apoptotic G-CSF target gene Bcl-X-L. In vitro, G-CSF enhances neurite outgrowth and branching capacity of hippocampal neurons. In vivo, G-CSF treatment results in improved functional connectivity of the injured spinal cord as measured by Mn2+-enhanced MRI. G-CSF also increased length of the dorsal corticospinal tract and density of serotonergic fibers cranial to the lesion center. Mice treated systemically with G-CSF as well as transgenic mice over-expressing G-CSF in the CNS exhibit a strong improvement in functional outcome as measured by the BBB score and gridwalk analysis. We show that G-CSF improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. We conclude that G-CSF constitutes a promising and feasible new therapy option for SCI
    Type of Publication: Journal article published
    PubMed ID: 20202082
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...