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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow stem cells are able to differentiate into nervous and endothelial cells. In our study, we found that administration of a bone marrow-stimulating factor (granulocyte colony-stimulating factor; G-CSF 50 microg/kg) decrease the brain infarct volume and enhance survival rate in a model of cerebral ischemia. Taken together, these data suggest a beneficial effect of a pharmacological endogenous bone marrow mobilization in the course of cerebral ischemia and open a new direction for cellular therapy strategy in stroke.
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PMID:Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia. 1250 90

Filgratism (granulocyte colony stimulating factor, G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) have replaced bone marrow (BM) as a preferred source of autologous stem cells, in light of the faster hematologic recovery and lesser supportive care requirement exhibited by PBPC transplants. Other hematopoietic stem cells, like the human umbilical cord blood-derived stem cells (hUCBs), and nonhematopoietic stem cells have been shown to improve motor function in rodent models of injury and degenerative disease. In the present study we transplanted either G-CSF-mobilized PBPCs or hUCBs in rats 24 h after permanent middle cerebral artery occlusion (MCAO), and assessed their behavioral abnormalities in spontaneous activity and spontaneous motor asymmetry. In both transplanted groups of rats we observed a significant reduction of the stroke-induced hyperactivity compared with nontransplanted, stroked animals. In addition, transplantation of G-CSF PBPC and hUCB cells prevented the development of extensive motor asymmetry. Our findings raise the possibility that PBPCs could provide a novel transplantation therapy to treat stroke.
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PMID:Mobilized peripheral blood cells administered intravenously produce functional recovery in stroke. 1291 Nov 32

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 anti-apoptotic 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.
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PMID:The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. 1600 67

G-CSF (Granulocyte-colony stimulating factor) is a hematopoietic growth factor that has been known for 20 years, and has been named for its role in the proliferation and differentiation of cells of the myeloic lineage. We have uncovered a novel spectrum of activities of G-CSF in the central nervous system. G-CSF and its receptor are expressed by neurons in many brain regions, and are upregulated upon experimental stroke. In neurons, G-CSF acts anti-apoptotically by activating several protective pathways. In vivo, G-CSF decreases infarct volumes in acute stroke models in rodents. Moreover, G-CSF stimulates neuronal differentiation of adult neural stem cells in the brain, and improves long-term recovery in more chronic stroke models. Thus, G-CSF is a novel neurotrophic factor, and a highly attractive candidate for the treatment of neurodegenerative conditions. Here we discuss this new property of G-CSF in contrast to its known functions in the hematopoietic system, summarize data from other groups on G-CSF's actions in cerebral ischemia, compare G-CSF to Erythropoietin (EPO) in the CNS, and highlight clinical implications.
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PMID:A role for G-CSF (granulocyte-colony stimulating factor) in the central nervous system. 1625 90

The hematopoietic and non-hematopoietic stem/progenitor cells harvested directly from the bone marrow (BM) or G-CSF mobilized peripheral blood were demonstrated to play an important role in regeneration of damaged organs (1, 2). Here, we asked if the stroke- or acute heart infarct-related stress triggers mobilization of stem/progenitor-enriched CD34(+)cells from the BM into the peripheral blood, which subsequently could contribute to regeneration of damaged tissues. To address this question the peripheral blood samples were harvested from patients with ischemic stroke during the first 24 h of manifestation of symptoms and on the second and sixth day afterwards or during the first 24 h of acute cardiac pain as well as on the second and sixth day of infarct. We measured in these patients (i) percentage of circulating hematopoietic stem/progenitor-enriched CD34(+) cells in peripheral blood by employing fluorescence activated cell sorter (FACS) and (ii) number of hematopoietic progenitor cells for the granulocyte-monocytic colony-forming unit (CFU-GM) and erythoid burst-forming unit (BFU-E) lineages circulating in peripheral blood. We concluded that stress related to ischemic stroke or acute myocardial infarction triggers the mobilization of hematopoietic stem/progenitor-enriched CD34(+) cells from the BM into peripheral blood. These circulating stem/progenitor-enriched CD34(+) cells may contribute to the regeneration of ischemic tissues, however, this possibility requires further studies.
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PMID:Human hematopoietic stem/progenitor-enriched CD34(+) cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction. 1631 57

Autologous hematopoietic stem cell transplantation (ASCT) has the potential to eliminate autoreactive lymphocytes and may represent a therapeutic option for patients with refractory autoimmune diseases. We describe a 19-year old woman with neuropsychiatric systemic lupus erythematodes (NPSLE) presenting with acute longitudinal myelitis and aseptic meningitis. Despite therapy with methylprednisolone and cyclophosphamide (CYC), recurrence of longitudinal myelitis and a disabling stroke-like relapse occurred. Hematopoietic stem cells were mobilized by CYC at 2 g/m2 and G-CSF. The patient was conditioned by CYC at 200 mg/kg and anti-thymocyte globulin and 3.6 x 10(6) CD34+ cells/kg were infused. Hematopoietic regeneration was observed on day 12 after ASCT. Currently, 18 months after ASCT, the patient is in clinical remission with no evidence for residual serological or neuroradiological activity of SLE. Although a longer follow-up will be needed to reliably assess the efficacy of ASCT in this patient, the present case demonstrates that ASCT may represent a therapeutic option for patients with severe NPSLE.
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PMID:Autologous blood stem cell transplantation in refractory systemic lupus erythematodes with recurrent longitudinal myelitis and cerebral infarction. 1668 65

Stroke is one of the leading causes of unnatural death and disability. No effective therapy is available. Recombinant human granulocyte colony-stimulating factor (rhG-CSF), as a mobilizing agent for bone marrow stem cells, can promote stem cell mobilization, homing to brain after cerebral ischemia. In the present study, the administration of G-CSF significantly increased number of CD34(+) cells in the marginal zone of the infarction. Rats receiving G-CSF had higher survival rate and lower infarction volume. Neurological behavior was improved, and the expression of fibronectin in the ischemic brain was increased, as compared to rats treated with vehicle. To mimic the ischemia-reperfusion injury in experimental animals, we employed hippocampal slice cultures that were first treated with oxygen and glucose deprivation (OGD) and then with oxygen-glucose resupply, finding that fibronectin significantly increased the neurite outgrowth of OGD hippocampal slices, upregulated the expression of Bcl-2 protein, and ameliorated the ultrastructure damage of OGD hippocampal slices.
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PMID:Fibronectin and neuroprotective effect of granulocyte colony-stimulating factor in focal cerebral ischemia. 1681 50

Increased vascular permeability causing vasogenic brain edema is characteristic for many acute neurological diseases such as stroke, brain trauma, and meningitis. Src family kinases, especially c-Src, play an important role in regulating blood-brain barrier permeability in response to VEGF, but also mediate leukocyte function and cytokine signalling. Here we demonstrate that pharmacological inhibition of Src or c-Src deficiency does not influence cerebrospinal fluid (CSF) pleocytosis, brain edema formation, and bacterial outgrowth during experimental pneumococcal meningitis despite the increased cerebral expression of inflammatory chemokines, such as IL-6, CCL-9, CXCL-1, CXCL-2 and G-CSF as determined by protein array analysis. In contrast, inhibition of Src significantly reduced brain edema formation, lesion volume, and clinical worsening in cold-induced brain injury without decreasing cytokine/chemokine expression. While brain trauma was associated with increased cerebral VEGF formation, VEGF levels significantly declined during pneumococcal meningitis. Therefore, we conclude that in brain trauma blood-brain barrier tightness is regulated by the VEGF/Src pathway whereas c-Src does not influence brain edema formation and leukocyte function during bacterial meningitis.
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PMID:Differential regulation of blood-brain barrier permeability in brain trauma and pneumococcal meningitis-role of Src kinases. 1701 Mar 40

In several experimental studies of cerebral ischaemia, G-CSF (granulocyte colony-stimulating factor) exerted neuroprotective effects through different mechanisms, including mobilization of haemopoietic stem cells, anti-apoptosis, neuronal differentiation, angiogenesis and anti-inflammation. Hence, G-CSF not only inhibits neuron death, but also generates 'new' neural tissue formation. A small pilot trial reports on the safety and feasibility of G-CSF therapy in stroke patients. According to this evidence, we can speculate that G-CSF, being used either alone or in combination with another agent, should have a dual activity beneficial both to acute neuronal protection and long-term plasticity after cerebral ischaemia, thus proposing that G-CSF is an ideal new drug for stroke and neurodegenerative diseases.
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PMID:G-CSF and neuroprotection: a therapeutic perspective in cerebral ischaemia. 1707 13

Stroke remains a leading cause of death and disability worldwide. An increasing number of animal studies and preclinical trials have, however, provided evidence that regenerative cell-based therapies can lead to functional recovery in stroke patients. Stem cells can differentiate into neural lineages to replace lost neurons. Moreover, they provide trophic support to tissue at risk in the penumbra surrounding the infarct area, enhance vasculogenesis, and help promote survival, migration, and differentiation of the endogenous precursor cells after stroke. Stem cells are highly migratory and seem to be attracted to areas of brain pathology such as ischemic regions. The pathotropism may follow the paradigm of stem cell homing to bone marrow and leukocytes migrating to inflammatory tissue. The molecular signaling therefore may involve various chemokines, cytokines, and integrins. Among these, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling is required for the interaction of stem cells and ischemia-damaged host tissues. SDF-1 is secreted primarily by bone marrow fibroblasts and is required for BMSC homing to bone marrow. Overexpression of SDF-1 in ischemic tissues has been found to enhance stem cell recruitment from peripheral blood and to induce neoangiogenesis. Furthermore, SDF-1 expression in the lesioned area peaked within 7 days postischemia, in concordance with the time window of G-CSF therapy for stroke. Recent data have shown that SDF-1 expression is directly proportional to reduced tissue oxygen tension. SDF-1 gene expression is regulated by hypoxic-inducible factor-1 (HIF-1), a hypoxia-dependent stabilization transcription factor. Thus, ischemic tissue may recruit circulating progenitors regulated by hypoxia through differential expression of HIF-lalpha and SDF-1. In addition to SDF-1, beta2-integrins also play a role in the homing of hematopoietic progenitor cells to sites of ischemia and are critical for their neovascularization capacity. In our recent report, increased expression of beta1-integrins apparently contributed to the local neovasculization of the ischemic brain as well as its functional recovery. Identification of the molecular pathways involved in stem cell homing into the ischemic areas could pave the way for the development of new treatment regimens, perhaps using small molecules, designed to enhance endogeneous mobilization of stem cells in various disease states, including chronic stroke and other neurodegenerative diseases. For maximal functional recovery, however, regenerative therapy may need to follow combinatorial approaches, which may include cell replacement, trophic support, protection from oxidative stress, and the neutralization of the growth-inhibitory components for endogenous neuronal stem cells.
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PMID:Regenerative therapy for stroke. 1747 98


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