Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood-derived CD34(+) cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34(+) cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.
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PMID:Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. 1528 94

Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34-, and CD45-) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce cerebral infarction volume and improve functional outcome.
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PMID:Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. 1673 Mar 52

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

The present study investigated effects of human umbilical cord blood derived CD34+ cells on sensorimotor, cognitive, and histological outcome in rats following focal cerebral ischemia. Halothane anesthetized adult male Wistar rats were subjected to transient or permanent occlusion of the middle cerebral artery (MCAO) followed by intravenous administration of CD34+ cells (5 x 10(5) or 2 x 10(6)) after 24 h recovery. The beam-walking and cylinder tests were used to assess sensorimotor function, and Morris water-maze examined cognitive performance during a 25 day follow-up period. Subsequently, rats were perfused for measurement of infarct volumes and detection of CD34' cells in the brain by immunohistochemistry (MAB1281). MCAO rats showed minor or no spontaneous recovery in sensorimotor function during the follow-up. The recovery profile was similar in MCAO controls and in MCAO rats that received CD34+ cells, although CD34+ cells seemed to improve the use of impaired forelimb. There was also a trend toward improved water-maze performance by CD34+ cells in transient MCAO rats. Infarct volumes assessed from Nissl-stained sections on postoperative day 25 did not differ between the experimental groups. MAB 1281-positive cells were not detected in the brain of MCAO rats that received CD34+ cells. The present study suggests that CD34+ cells might improve functional outcome in MCAO rats after systemic administration, but do not significantly provide neuroprotection.
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PMID:Human cord blood CD34+ cells and behavioral recovery following focal cerebral ischemia in rats. 1726 91

Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
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PMID:Human umbilical cord blood-derived CD34+ cells cause attenuation of multiorgan dysfunction during experimental heatstroke. 1750 7

The administration of CD34-positive cells after stroke has been shown to have a beneficial effect on functional recovery by accelerating angiogenesis and neurogenesis in rodent models. Granulocyte colony-stimulating factor (G-CSF) is known to mobilize CD34-positive cells from bone marrow and has displayed neuroprotective properties after transient ischemic stress. This led us to investigate the effects of G-CSF administration after stroke in mouse. We utilized permanent ligation of the M1 distal portion of the left middle cerebral artery to develop a reproducible focal cerebral ischemia model in CB-17 mice. Animals treated with G-CSF displayed cortical atrophy and impaired behavioral function compared with controls. The negative effect of G-CSF on outcome was associated with G-CSF induction of an exaggerated inflammatory response, based on infiltration of the peri-infarction area with CD11b-positive and F4/80-positive cells. Although clinical trials with G-CSF have been started for the treatment of myocardial and limb ischemia, our results indicate that caution should be exercised in applying these results to cerebral ischemia.
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PMID:Granulocyte colony-stimulating factor has a negative effect on stroke outcome in a murine model. 1761 44

Maintenance of uninterrupted cerebral circulation is critical for neural homeostasis. The level of circulating CD34-positive (CD34(+)) cells has been suggested as an index of cerebrovascular health, although its relationship with cognitive function has not yet been defined. In a group of individuals with cognitive impairment, the level of circulating CD34(+) cells was quantified and correlated with clinical diagnoses. Compared with normal subjects, a significant decrease in circulating CD34(+) cells was observed in patients with vascular-type cognitive impairment, although no significant change was observed in patients with Alzheimer's-type cognitive impairment who had no evidence of cerebral ischemia. The level of cognitive impairment was inversely correlated with numbers of circulating CD34(+) cells in patients with vascular-type cognitive impairment, but not Alzheimer's type. We propose that the level of circulating CD34(+) cells provides a marker of vascular risk associated with cognitive impairment, and that differences in the pathobiology of Alzheimer's- and vascular-type cognitive impairment may be mirrored in levels of circulating CD34(+) cells in these patient populations.
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PMID:Circulating CD34-positive cells provide a marker of vascular risk associated with cognitive impairment. 1768 16

The field of cell-based transplantation has expanded considerably and is poised to become an established cardiovascular therapy in the near future. In this review, we will focus on endothelial progenitor cells (EPCs), which are immature cells capable of differentiating into mature endothelial cells. EPCs share many surface marker antigens such as CD34, AC133, Flk-1, etc. with hematopoietic stem cells (HSCs) and the major source of EPCs as well as HSCs is the bone marrow (BM). BM-derived EPCs are mobilized into peripheral blood and recruited to the foci of pathophysiological neovascularization and reendothelialization, thereby contributing to vascular regeneration. Severe EPC dysfunction is an indicator of poor prognosis and severe endothelial dysfunction. Indeed, number of circulating EPCs and their migratory activity are reduced in patients with diabetes, coronary artery disease (CAD), or subjects with multiple coronary risk factors. Effective neovascularization induced by EPC transplantation for hindlimb, myocardial, and cerebral ischemia has been demonstrated in many preclinical studies, and early clinical trials of EPC transplantation in chronic and acute CAD indicate safety and feasibility of myocardial cell-based therapies. For therapeutic reendothelialization in patients undergoing percutaneous coronary intervention, CD34 antibody-coated stents have been used clinically to capture circulating EPCs at the injury sites and enhance reendothelialization and safety of stents. Further development in cell processing technology for efficient isolation, expansion, mobilization, recruitment, and transplantation of EPCs into target tissues are underway and expected to be tested in clinical trials in the near future.
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PMID:Role of progenitor endothelial cells in cardiovascular disease and upcoming therapies. 1789 61

We attempted to assess the prophylactic effect of human umbilical cord blood-derived CD34(+) cells in experimental heatstroke. Anesthetized rats, 1 day before heat stress, were divided into 2 major groups and given CD34(-) cells (defined by 1 x 10(6) human cord blood lymphocytes and monocytes that contained <0.2% CD34(+) cells) or CD34(+) cells (defined by 1 x 10(6) human cord blood lymphocytes and monocytes that contained >95% CD34(+) cells). They were exposed to ambient temperature of 43 degrees C for 70 min to induce heatstroke. When the CD34(-) cells-treated or untreated rats underwent heat stress, their survival time values were found to be 20-24 min. Pretreatment with CD34(+) cells significantly increased survival time (123-351 min). As compared with normothermic controls, all CD34(-) cells-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, these heatstroke reactions all were significantly suppressed by CD34(+) cells pretreatment. In addition, the levels of interleukin-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34(+) cell administration during heatstroke. Our data indicate that human umbilical cord-derived CD34(+) cells can be used as a prophylactic agent for experimental heatstroke.
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PMID:Human umbilical cord blood-derived CD34+ cells can be used as a prophylactic agent for experimental heatstroke. 1818 24

Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1 mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for beta-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia.
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PMID:Neuroprotective effects of mesenchymal stem cells derived from human embryonic stem cells in transient focal cerebral ischemia in rats. 1920 81


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