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)

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

The pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) remains unknown. Besides vasospasm, microthrombosis might have an important function. As in patients with thrombotic thrombocytopenic purpura an A Disintegrin And Metalloprotease with ThromboSpondin repeats-13 (ADAMTS13) deficiency leads to higher concentrations of large von Willebrand factor (vWF) multimers resulting in microthrombosis, our purpose was to compare ADAMTS13 and vWF in patients with and without DCI after aneurysmal SAH. We measured ADAMTS13 activity, vWF antigen, vWF propeptide, and vWF ristocetin cofactor activity in plasma at standard intervals. Thirty-one patients were included. Eleven patients (35%) developed DCI. No differences were observed in baseline characteristics between patients with and without DCI. Patients with DCI had a stronger decrease in ADAMTS13 activity, and a more profound increase in vWF antigen, vWF propeptide, and vWF activity in the first few days after the hemorrhage (P-values for difference in polynomial time trend 0.0001, 0.020, 0.004, and 0.188, respectively). No indication of correlation between vWF antigen and ADAMTS13 was found (r=-0.027, P=0.736). Our results suggest that microthrombosis has a role in the pathogenesis of DCI, as a result of decreased ADAMTS13 activity and endothelium dysfunction.
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PMID:Reduced ADAMTS13 activity in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. 1958 92

The present study examined the effects of human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs) delivered through the basilar artery in a canine thromboembolic brain ischemia model. Cerebral ischemia was induced through occlusion of the middle cerebral artery by injecting thrombus emboli into 10 beagles. In the HUCBC group (n = 5), 1 x 10(6) HUCB-derived MSCs were transplanted through the basilar artery 1 day after ischemic induction using an endovascular interventional approach. In the control group (n = 5), phosphate-buffered saline (PBS) was injected in the same manner in as the HUCBC group. Upon neurobehavioral examination, earlier recovery was observed in the HUCBC group. The HUCBC group showed a decrease in the infarction volume at 1 week after cerebral ischemic induction, whereas the control group showed an increase in the infarction volume at 1 week, by magnetic resonance image analysis. Transplanted cells had differentiated into neurons and astrocytes and were observed in and around endothelial cells that were positive for von Willebrand factor (vWF). HUCB-derived MSCs expressed neuroprotective factors, such as brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), at 4 weeks after the transplantation. The transplanted cells demonstrated their efficacy by reducing the infarction lesion volume and through earlier recovery from the neurological deficit. These results suggest that intraarterial transplantation of HUCB-derived MSCs could be useful in clinical treatment of cerebral ischemia.
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PMID:Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia. 1964 3

Stroke is a leading cause of death and disability. The only therapy available is recombinant tissue plasminogen activator, but side effects limit its use. Platelets play a crucial role during stroke, and the inflammatory reaction promotes neurodegeneration. von Willebrand factor (VWF), an adhesion molecule for platelets, is elevated in patients with acute stroke. The activity of VWF is modulated by ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) that cleaves VWF to smaller less-active forms. We recently documented that ADAMTS13 negatively regulates both thrombosis and inflammation. We report that deficiency or reduction of VWF reduces infarct volume up to 2-fold after focal cerebral ischemia in mice, thus showing the importance of VWF in stroke injury. In contrast, ADAMTS13 deficiency results in larger infarctions, but only in mice that have VWF. Importantly, infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Furthermore, recombinant ADAMTS13 did not enhance bleeding in a hemorrhagic stroke model. Our findings show the importance of VWF in regulating infarction and suggest that recombinant ADAMTS13 could be considered as a new therapeutic agent for prevention and/or treatment of stroke.
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PMID:von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. 1968 10

We evaluated the effects of intranasal vascular endothelial growth factor VEGF on neurological function and angiogenesis in ischemic boundary following cerebral ischemia. Sprague-Dawley rats were randomized into sham operation group (n = 9), VEGF group (n = 18), and control group (n = 18). The VEGF and control rats were intranasally administered (IN) with VEGF or saline, starting three days after middle cerebral artery occlusion (MCAO) and daily. Neurological scores were obtained at 1, 7, and 14 days after MCAO. Rats were sacrificed at 14 days, the von Willebrand factor (vWF) immunoreactive, BrdU(+)/vWF(+) cells, and microvessels were evaluated respectively. Compared to the control rats, intranasal administration of VEGF improved behavioral recovery, and increased the number of vWF(+), BrdU(+)/vWF(+) cells, and FITC-dextran perfused microvessels in ischemic boundary (p < .01). Our data suggest that intranasal administration of VEGF may induce angiogenesis in ischemic boundary and improve behavioral recovery following cerebral ischemia in rats, which may provide a powerful strategy for stroke.
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PMID:VEGF promotes angiogenesis and functional recovery in stroke rats. 2059 Mar 86

Neurogenesis and angiogenesis are two important processes that may contribute to the repair of brain injury after stroke. This study was designed to investigate whether transplantation of human embryonic neural stem cells (NSCs) into cortical peri-infarction 24h after ischemia effects cell proliferation in the subventricular zone (SVZ) and angiogenesis in the peri-infarct zone. NSCs were prepared from embryonic human brains at 8 weeks gestation. Focal cerebral ischemia was induced by permanent occlusion of the middle cerebral artery of adult rats. Animals were randomly divided into two groups (n=30, each) at 24h after ischemia: NSC-grafted and medium-grafted groups. Toluidine blue staining and 5'-bromo-2'-deoxyuridine (BrdU) or von Willebrand factor (vWF) immunohistochemistry were performed at 7, 14 and 28 days after transplantation. NSC transplantation increased the number of BrdU-positive cells in the ischemic ipsilateral SVZ compared with the medium control at 7 days (P<0.01). This difference in SVZ cell proliferation persisted at 14 days (P<0.01), but was not significant at 28 days (P>0.05). In addition, angiogenesis, as indicated by BrdU and vWF staining in cortical peri-infarct regions, was augmented by 46% and 65% in NSC-grafted rats versus medium-grafted rats at 7 and 14 days, respectively (P<0.05). However, this increase became non-significant at 28 days (P>0.05). Our results indicate that NSC transplantation enhances endogenous cell proliferation in the SVZ and promotes angiogenesis in the peri-infarct zone, even if it is performed in the acute phase of ischemic injury.
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PMID:Human embryonic neural stem cell transplantation increases subventricular zone cell proliferation and promotes peri-infarct angiogenesis after focal cerebral ischemia. 2117 62

Thrombus formation is of paramount importance in the pathophysiology of acute ischemic stroke. Current antithrombotics used to treat or prevent cerebral ischemia are only moderately effective or bear an increased risk of severe bleeding. von Willebrand factor (VWF) has long been known to be a key player in thrombus formation at sites of vascular damage. While the association between VWF and coronary heart disease has been well studied, knowledge about the role of VWF in stroke is much more limited. However, in recent years, an increasing amount of clinical and preclinical evidence has revealed the critical involvement of VWF in stroke development. This review summarizes the latest insights into the pathophysiologic role of VWF-related processes in ischemic brain injury under experimental conditions and in humans. Potential clinical merits of novel inhibitors of VWF-mediated platelet adhesion and activation as powerful and safe tools to combat thromboembolic disorders including ischemic stroke are discussed. Preclinical and clinical evidence illustrates an important role of VWF in ischemic stroke, suggesting that VWF could become a promising target in stroke therapy.
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PMID:von Willebrand factor: an emerging target in stroke therapy. 2218 Feb 50

Stroke is caused by vascular dysfunction and currently there are no effective therapeutics to stroke induced brain damage. In contrast to an intense emphasis on neuroprotection, relatively few studies have addressed means of vascular protection in cerebral ischemia. Here we discovered that the ligand to immidazolin receptor, 2-BFI, not only provided potent neuroprotection during middle cerebral artery occlusion in rat, which confirmed our previous reports, but also protected the integrity of the cerebral vasculature. Treatment with 2-BFI twice daily after the occlusion of the middle cerebral artery for 14 d significantly improved the neurological deficits, reduced brain infarction, and importantly, protected the cerebral vasculature as evidenced by the increased expression of an endothelial marker, von Willebrand factor, and better preservation of the cerebral vasculature, as viewed under a confocal microscope on rat brain perfused with FITC-labeled dextran. These results indicated that 2-BFI contributes to protection of neurovasculature. Understanding the molecular mechanisms could eventually lead to development of more effective therapies for stroke.
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PMID:Neurovascular protection conferred by 2-BFI treatment during rat cerebral ischemia. 2277 26

Long-chain n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), have been shown to reduce ischemic neuronal injury. We investigated the effects of ethyl-EPA (EPA-E) on ischemic brain damage using a rat transient focal cerebral ischemia model. Male Sprague-Dawley rats (n=105) were subjected to 90 min of focal cerebral ischemia. EPA-E (100mg/kg/day) or vehicle was administered once a day for 3, 5 or 7 days prior to ischemia. Different withdrawal intervals of 3, 5, and 7 days prior to ischemia following 7-day pretreatment with EPA-E or vehicle were also examined. In addition, post-ischemic administration of EPA-E was investigated. Pretreatment with EPA-E for 7 and 5 days, but not 3 days, showed significant infarct volume reduction and neurological improvements when compared with vehicle pretreatment. In addition, withdrawal of EPA-E administration for 3 days, but not 5 and 7 days, also demonstrated significant infarct volume reduction and neurological improvements when compared with vehicle treatment. Post-ischemic treatment of EPA-E did not show any neuroprotection. Immunohistochemistry revealed that 7-day pretreatment with EPA-E significantly reduced cortical expression of 8-hydroxydeoxyguanosine (maker for oxidative DNA damage), 4-hydroxy-2-nonenal (maker for lipid peroxidation), phosphorylated adducin (marker for Rho-kinase activation) and von Willebrand factor (endothelial marker) when compared with vehicle pretreatment. In addition, phosphorylated adducin expression co-localized with von Willebrand factor immunoreactivity. The present study established the neuroprotective effect of EPA-E on ischemic brain damage following transient focal cerebral ischemia in rats, which may be involved in the suppression of oxidative stress and endothelial Rho-kinase activation.
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PMID:Therapeutic impact of eicosapentaenoic acid on ischemic brain damage following transient focal cerebral ischemia in rats. 2364 59

Persimmon leaf flavonoid has been shown to enhance brain ischemic tolerance in mice, but its mechanism of action remains unclear. The bilateral common carotid arteries were occluded using a micro clip to block blood flow for 10 minutes. After 10 minutes of ischemic preconditioning, 200, 100, and 50 mg/kg persimmon leaf flavonoid or 20 mg/kg ginaton was intragastrically administered per day for 5 days. At 1 hour after the final administration, ischemia/reperfusion models were estab-lished by blocking the middle cerebral artery for 2 hours. At 24 hours after model establishment, compared with cerebral ischemic rats without ischemic preconditioning or drug intervention, plasma endothelin, thrombomodulin and von Willebrand factor levels significantly decreased and intercel-lular adhesion molecule-1 expression markedly reduced in brain tissue from rats with ischemic pre-conditioning. Simultaneously, brain tissue injury reduced. Ischemic preconditioning combined with drug exposure noticeably improved the effects of the above-mentioned indices, and the effects of 200 mg/kg persimmon leaf flavonoid were similar to 20 mg/kg ginaton treatment. These results indicate that ischemic preconditioning produces tolerance to recurrent severe cerebral ischemia. However, persimmon leaf flavonoid can elevate ischemic tolerance by reducing inflammatory reactions and vascular endothelial injury. High-dose persimmon leaf flavonoid showed an identical effect to ginaton.
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PMID:Persimmon leaf flavonoid promotes brain ischemic tolerance. 2520 73


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