Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND Hypoxic-ischemic brain injury in the perinatal period is a main cause of perinatal mortality and neurologic complications in neonates and children. Recent studies have focused on the neuroprotective effect of anesthetic drugs. The volatile anesthetic isoflurane has been shown to exert neuroprotective effects in cerebral ischemia. Mangiferin is a natural polyphenol with various pharmacological properties, including antioxidant and ant-tumor effects. This study aimed to determine whether mangiferin potentiates the neuroprotective effects of isoflurane and also if mangiferin when administered alone exerts neuroprotective effects following hypoxic-ischemic brain injury. MATERIAL AND METHODS Sprague-Dawley rats were subjected to cerebral hypoxic ischemia on postnatal day 10 (P10). Mangiferin (50, 100, or 200 mg/kg b.w.) was intragastrically administered from P3 to P12 and 1 h prior to insult on the day of ischemic induction. At 3 h after hypoxia-ischemia (HI) insult, separate groups of rat pups were exposed to isoflurane (1.5%) for 6 h. Following 48 h of HI, the rats were sacrificed and brain tissues were used for analysis. RESULTS Mangiferin treatment attenuated neuronal apoptosis and reduced cerebral infarct volume. The expression of cleaved caspase-3 and apoptotic cascade proteins were regulated. The levels of reactive oxygen species (ROS) and malondialdehyde were reduced by mangiferin and/or isoflurane exposure. The levels of antioxidant glutathione were considerably raised under HI injury, which was modulated by mangiferin and isoflurane exposure. The PI3K/Akt signaling pathway, which was downregulated following HI insult, was activated by mangiferin and/or isoflurane. CONCLUSIONS This study reveals the potent neuroprotective efficacy of mangiferin against HI-induced brain injury via effectively modulating apoptotic pathways, ROS levels, and PI3K/Akt cascades while potentiating protective effects of isoflurane.
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PMID:Mangiferin Potentiates Neuroprotection by Isoflurane in Neonatal Hypoxic Brain Injury by Reducing Oxidative Stress and Activation of Phosphatidylinositol-3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR) Signaling. 3033 64

Critical limb ischemia (CLI) is a common cause of high vascular morbidity and mortality. Monitoring the development and treatment response of hindlimb ischemia (HI) in an animal model enables a better understanding of the pathological mechanisms underlying CLI, and evaluation of the efficacy of novel therapeutic approaches. Matrix metalloproteinase (MMP) activity is essential for remodeling of ischemic tissue including extracellular matrix degradation and angiogenesis. Herein, a mouse HI model is established and subjected to noninvasive optical imaging with a novel and ultra-sensitive MMP activatable probe, termed MMP-P12, for analyzing the development and treatment response of HI. Our results show that angiogenesis development during HI was well correlated with MMP-2 activity alteration as examined by western blot, histological staining and MMP-P12 fluorescence signal recovery. Moreover, vascular endothelial growth factor (VEGF) mediated HI treatment was also monitored by MMP-P12. Up-regulated MMP-2 expression and an enhancement of angiogenesis were observed after VEGF treatment, which peaked at 7 days after the treatment. Overall, our results showed that MMP-2 plays an important role in the monitoring of angiogenesis during HI development and therapy. Application of MMP-P12 to visualize MMP-2 activity alteration can serve as a promising noninvasive optical imaging strategy to monitor angiogenesis and its response to therapy in CLI.
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PMID:Noninvasive monitoring of the development and treatment response of ischemic hindlimb by targeting matrix metalloproteinase-2 (MMP-2). 3148 34

Retinopathy of prematurity (ROP) is a disorder of the developing retina of preterm infants. ROP can lead to blindness because of abnormal angiogenesis that is the result of suspended vascular development and vaso-obliteration leading to severe retinal stress and hypoxia. We tested the hypothesis that the use of the human progenitor cell combination, bone marrow-derived CD34+ cells and vascular wall-derived endothelial colony-forming cells (ECFCs), would synergistically protect the developing retinal vasculature in a mouse model of ROP, called oxygen-induced retinopathy (OIR). CD34+ cells alone, ECFCs alone, or the combination thereof were injected intravitreally at either P5 or P12 and pups were euthanized at P17. Retinas from OIR mice injected with ECFCs or the combined treatment revealed formation of the deep vascular plexus (DVP) while still in hyperoxia, with normal-appearing connections between the superficial vascular plexus (SVP) and the DVP. In addition, the combination of cells completely prevented aberrant retinal neovascularization and was more effective anatomically and functionally at rescuing the ischemia phenotype than either cell type alone. We show that the beneficial effects of the cell combination are the result of their ability to orchestrate an acceleration of vascular development and more rapid ensheathment of pericytes on the developing vessels. Lastly, our proteomic and transcriptomic data sets reveal pathways altered by the dual cell therapy, including many involved in neuroretinal maintenance, and principal component analysis (PCA) showed that cell therapy restored OIR retinas to a state that was closely associated with age-matched normal retinas. Together, these data herein support the use of dual cell therapy as a promising preventive treatment for the development of ROP in premature infants.
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PMID:Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model. 3167 44

We have demonstrated previously that activation of either the ETA or ETB receptor can induce acute electrographic seizures following the intrahippocampal infusion of endothelin-1 (ET-1) in immature (P12) rats. We also demonstrated that activation of the ETA receptor is associated with marked focal ischemia, while activation of the ETB receptor is not. Exploring the mechanisms underlying seizures induced by these two ET-1 receptor interactions can potentially provide insight into how focal ischemia in immature animals produces seizures and whether ischemiarelated seizures differ from seizures not associated with ischemia. To explore these seizure mechanisms we used microdialysis to determine biomarkers associated with seizures in P12 rats following the intrahippocampal infusion of two different agents: (1) ET-1, which activates both the ETA and ETB receptors and causes focal ischemia and (2) Ala-ET-1, which selectively activates only the ETB receptor and does not cause ischemia. Our results show that seizures associated with combined ETA and ETB receptor activation (and ischemia) have a different temporal distribution and microdialysis profile from seizures associated with ETB activation alone (and without ischemia). Seizures with combined activation peak within the first hour after infusion and the microdialysis profile is characterized by a significant increase in the ratio of glutamic acid to GABA. By contrast, seizures with activation of only the ETB receptor peak in the second hour after infusion and microdialysis shows a significant increase in the ratio of leukotriene B4 to prostaglandin E2. These findings suggest that ischemia-related seizures in immature animals involve an imbalance of excitation and inhibition, while non-ischemiarelated seizures involve an inflammatory process resulting from an excess of leukotrienes.
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PMID:Electrographic seizures induced by activation of ETA and ETB receptors following intrahippocampal infusion of endothelin-1 in immature rats occur by different mechanisms. 3208 51


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