UMLS:C0917798 - FACTA Search

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Query: UMLS:C0917798 (cerebral ischemia)
17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroglobin (Ngb), a vertebrate globin expressed primarily in neurons, is induced by and protects against neuronal hypoxia and cerebral ischemia. To investigate the spectrum and mechanism of Ngb's neuroprotective action, we studied the effect of transgenic overexpression of Ngb on NMDA and beta-amyloid (Abeta) toxicity in murine cortical neuron cultures in vitro and on the phenotype of Alzheimer's disease (AD) transgenic (APP(Sw,Ind)) mice. Compared with cortical neuron cultures from wild-type mice, cultures from Ngb-overexpressing transgenic (Ngb-Tg mice) were resistant to the toxic effects of NMDA and Abeta(25-35), as measured by polarization of cell membrane lipid rafts, mitochondrial aggregation, lactate dehydrogenase release, and nuclear fragmentation. In addition, compared with APP(Sw,Ind) mice, double-transgenic (Ngb-Tg x APP(Sw,Ind)) mice showed reductions in thioflavin-S-stained extracellular Abeta deposits, decreased levels of Abeta(1-40) and Abeta(1-42), and improved behavioral performance in a Y-maze test of spontaneous alternations. These findings suggest that the spectrum of Ngb's neuroprotective action extends beyond hypoxic-ischemic insults. Ngb may protect neurons from NMDA and Abeta toxicity by inhibiting the formation of a death-signaling membrane complex, and interventions that increase Ngb expression could have therapeutic application in AD and other neurodegenerative disorders.
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PMID:Neuroglobin attenuates beta-amyloid neurotoxicity in vitro and transgenic Alzheimer phenotype in vivo. 1802 70

This study was to investigate the protective effects and possible mechanisms of total flavones of rhododendra (TFR) against cerebral ischemia reperfusion injury in rats and mice. Cerebral ischemia/reperfusion injury was induced by occluding the right middle cerebral artery (MCA). Infarct volume, neurological deficit, brain water content, levels of malondialdehyde (MDA), nitric oxide (NO) contents, lactate dehydrogenase (LDH) activity in plasma and brain, levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and mRNA expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in brain were evaluated 7 or 10 days after treatment. TFR significantly reduced infarct volume, ameliorated the neurological deficit and reduced the brain water content. The activities of SOD, LDH and GPX in brain were enhanced, while the activity of LDH in plasma and the contents of MDA and NO in plasma and brain were decreased. While, the expression of iNOS and nNOS mRNA in brain were down-regulated, the expression of eNOS mRNA in the brain was up-regulated. These results suggest that TFR has protective effects for cerebral injury in rats and mice, which might be associated with its antioxidant properties and ability to regulate the expression of NOS isoforms.
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PMID:Protective effects of total flavones of rhododendra on cerebral ischemia reperfusion injury. 1845 65

Cerebral ischemia/reperfusion involves inflammatory process and naloxone is able to reduce infarct volume and has been used as a therapeutic agent for brain injury. Hypoxia induces the immediate early genes (IEGs) rapidly and transiently that may initiate a cascade of cellular responses that are necessary for survival and normal function. However, the protective effect of naloxone on ischemic/hypoxic neuronal cells was only partly studied. Thus, the effects of naloxone on oxygen- and glucose-deprivation (OGD) and OGD followed by reoxygenation (OGD/R) on the expression of IEGs were examined in PC12 cells. The result showed that lactate dehydrogenase (LDH) released in the media was reduced by naloxone. The temporal response of IEG mRNA encoding c-fos, c-jun, nur77, and zif268 was induced with different degree of intensity following hypoxia, whereas the level of GAPDH mRNA was relatively constant. However, these signals of c-fos, c-jun, and nur77 by hypoxia were reduced significantly by naloxone. Treatment with OGD also activated mitogen-activated protein kinase (MAPK) pathway. The induction of c-fos, c-jun, nur77, and zif268 by hypoxia was inhibited by naloxone (0.1 microM) and MAPK inhibitors (10 microM of U0126, D98059, SB203580). However, naloxone increased the expression of ERK1/2 by OGD concomitantly diminished the LDH release. Thus, the present studies demonstrated that OGD induced IEGs including c-fos, c-jun, nur77, and zif268 and MAPK signaling pathways were regulated differently by naloxone.
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PMID:Effect of naloxone on the induction of immediately early genes following oxygen- and glucose-deprivation in PC12 cells. 1845 20

Antioxidants have been the focus of studies for developing neuroprotective agents to be used in the therapy for stroke, which is an acute and progressive neurodegenerative disorder and is the second leading cause of death throughout the world. In fact, many herbal antioxidants have been developed in in vitro and in vivo experiments and some of these have been tested in clinical studies of stroke. Embelia ribes have been reported to have antioxidant and antidiabetic effects. In addition to these effects, this study was designed to investigate the neuroprotective effect of ethanolic extract of E. ribes Burm fruits on middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Male Wistar albino rats were fed ethanolic E. ribes extract (100 and 200 mg/kg body weight; p.o.) for 30 days. After 30 days of feeding, all animals were anaesthetized with chloral hydrate (400 mg/kg, i.p.). The right middle cerebral artery was occluded with a 4-0 suture for 2 h. The suture was removed after 2 h to allow reperfusion injury. Ischemia followed by reperfusion in ischemic group rats significantly (P < 0.001) reduced the grip strength activity and non-enzymatic (reduced glutathione, GSH) and enzymatic [glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)] antioxidant levels in hippocampus and frontal cortex compared to sham-operated rats. Further, serum lactate dehydrogenase (LDH) and thiobarbituric acid reactive substance (TBARS) levels in hippocampus and frontal cortex were significantly increased in ischemic group compared to sham-operated rats. Furthermore, ethanolic E. ribes extracts pretreatment significantly (P < 0.001) increased the grip strength activity, and GSH, GPx, GR and GST levels in hippocampus and frontal cortex with significant decrease in LDH levels in serum and TBARS levels in hippocampus and frontal cortex compared to MCAO + vehicle group rats. The data from this study suggest that chronic treatment with ethanolic E. ribes extract enhances the antioxidant defense against MCAO- induced focal cerebral ischemia in rats and exhibits neuroprotective activity.
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PMID:Evaluation of antioxidant and neuroprotective effect of ethanolic extract of Embelia ribes Burm in focal cerebral ischemia/reperfusion-induced oxidative stress in rats. 1848 49

An increasing number of reports suggest the involvement of oxidative stress in neurodegenerative diseases where the increased formation of reactive oxygen species (ROS) leads to neuronal damage and cell death. Dopamine may contribute to neurodegenerative disorders such as Parkinson's disease and ischemia/reperfusion-induced damage. Monoamine oxidase (MAO) enzyme (particularly MAO-B) is responsible for metabolizing dopamine and plays an important role in oxidative stress through altering the redox state of neuronal and glial cells. MAO participates in the generation of hydroxyl radicals during ischemia/reperfusion. This suggests the possible use of MAO inhibitors as neuroprotective agents for treating ischemic injury. The protective effect of deprenyl (N-methyl-N-(1-methyl-2-phenyl-ethyl)-prop-2-yn-1-amine, CAS 14611-51-9) (2 and 10 mg/kg), a MAO-B inhibitor, and beta-carotene (10 and 20 mg/kg), a natural antioxidant, was examined in a rat model of cerebral ischemia. Ischemia was induced in rats by bilateral carotid artery occlusion for 1 h followed by declamping for another hour. The effect of the drugs on the brain activity of lactate dehydrogenase (LDH) and some of the oxidative stress biomarkers such as brain activity of superoxide dismutase (SOD) and catalase (CAT) enzymes and brain malondialdehyde (MDA) content was determined. In addition, the content of catecholamines such as noradrenaline (NA) and dopamine (DA) was determined. Deprenyl decreased the ischemia-induced elevation of LDH activity and MDA content and normalized the SOD activity. In addition, deprenyl increased the CAT activity back to normal, and increased the noradrenaline and dopamine content in the brain of rats. Beta-carotene administration ameliorated the effect of ischemia followed by reperfusion (I/R) demonstrated as decreasing the LDH activity and MDA content and by increasing the SOD activity. The drug also increased CAT activity in the brain of rats. However, beta-carotene did not alter the NA and DA content. These results indicate that deprenyl protected the rat brains against the ischemia-induced oxidative damage, an effect which might be explained through multiple mechanisms, possibly due to reduction of dopamine catabolism with a subsequent increased activity on dopaminergic D2 receptors and suppressing the action of ROS as well.
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PMID:Effect of MAO-B inhibition against ischemia-induced oxidative stress in the rat brain. Comparison with a rational antioxidant. 1854 Apr 77

Endogenic and transplanted neural progenitor cells (NPCs) can be activated by cerebral ischemia and take part in the regeneration of neural function. NF-kappaB was found activated in the same pathology procedure and was assumed to play a crucial role in regulating NPCs' physiology. But it is still not clear whether NF-kappaB is activated in NPCs in cerebral ischemia and what is the effect of NF-kappaB on NPCs when activated. Our previous work generated immortalized neural progenitor cells (INPCs) to provide simulation for NPCs. Then pcDNA3.1 transfected INPCs (INPCs/pcDNA3.1) and mutated IkappaBalpha gene transfected INPCs (INPCs/IkappaBalphaM) were generated. By western blotting and electrophoretic mobility shift assay mutated IkappaBalpha was found expressed in INPCs/IkappaBalphaM and repressed the activity of NF-kappaB in INPCs. No difference in the differentiation of INPCs/pcDNA3.1 and INPCs/IkappaBalphaM was found by western blotting and immunocytochemistry. Detected by MTT assay INPCs/IkappaBalphaM had a lower proliferation rate under normal conditions. The apoptosis rate and lactate dehydrogenase activity in the medium of INPCs/IkappaBalphaM were lower than INPCs/pcDNA3.1 after oxygen-glucose deprivation. Some NF-kappaB-driven cytokines were observed down-regulated in INPCs/IkappaBalphaM by real-time reverse transcription polymerase chain reaction. In our research NF-kappaB was found activated in INPCs after oxygen-glucose deprivation. NF-kappaB activity down-regulation represses proliferation of INPCs and improves their tolerance to oxygen-glucose deprivation.
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PMID:Mutated IkappaBalpha represses proliferation of immortalized neural progenitor cells and prevents their apoptosis after oxygen-glucose deprivation. 1877 81

Free radicals are known to cause secondary neuronal damage in cerebral ischemia/reperfusion (I/R). We investigated here the neuroprotective effect of resveratrol, a potent antioxidant present in grape seed, against cerebral I/R-induced mitochondrial dysfunctions in hippocampus. Transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia was used to induce brain infarction. Resveratrol (10(-7) g/kg) was given twice intravenously: 15 min pre-occlusion and at the time of reperfusion (2 h post-occlusion). Resveratrol significantly restored ATP content and the activity of mitochondrial respiratory complexes in resveratrol treated group which were severely altered in MCAO group. Western blot analysis showed a marked decrease in cytochrome c release as a result of resveratrol treatment. Electrophoretic migration of hippocampal genomic DNA showed a marked decrease in DNA fragmentation after resveratrol treatment. Notably, expression of Hsp70 and metallothionein (MT) was significantly higher in MCAO group but their expression was more significant in resveratrol treated group. The status of mitochondrial glutathione (GSH), glucose 6-phosphate dehydrogenase (G6-PD) and serum lactate dehydrogenase (LDH) was restored by resveratrol treatment with a significant decrease in mitochondrial lipid peroxidation (LPO), protein carbonyl and intracellular H(2)O(2) content. Resveratrol significantly improved neurological deficits assessed by different scoring methods. Also, the brain infarct volume and brain edema were significantly reduced. Histological analysis of CA1 hippocampal region revealed that resveratrol treatment diminished intercellular and pericellular edema and glial cell infiltration. The findings of this study highlight the ability of resveratrol in anatomical and functional preservation of ischemic neurovascular units and its relevance in the treatment of ischemic stroke.
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PMID:Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. 1902 23

Neurons depend for survival on local neurotrophic factors which act in an autocrine/paracrine manner. However, the effect of paracrine signaling of brain microvascular endothelial cells (BMECs) under pathological conditions on neuron survival is not fully understood. In this study we cultured rat BMECs and cortical neurons. BMECs were cultured in oxygen-glucose-deprived (OGD) conditions to mimic cerebral ischemia in vitro. The conditioned media of normal BMECs or OGD-injured BMECs were used to culture normal or injured neurons. Neuron activity, free Ca(2+) concentration, NMDA receptor status, mitochondrial membrane potential and cytochrome C release level were determined. The results showed: mitochondrial activity of injured neurons was significantly increased and lactate dehydrogenase (LDH) leakage was decreased (P<0.05) by grown in conditioned medium of normal BMECs. Inversely, mitochondrial activity of normal or injured neurons was decreased and LDH leakage was significantly increased (P<0.05) by grown in conditioned medium of injured BMECs. The changes in free Ca(2+) concentration, NMDA receptor status, mitochondrial membrane potential and cytochrome C release level were consistent with the changes in neuronal activity. These findings suggest that the conditioned medium of normal BMECs has a neuroprotective effect. However, this protective effect was lost after BMECs injury; in fact, the conditioned medium became neurotoxic. Therefore, it appears that early recovery of BMECs might be helpful for neuron survival.
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PMID:The impact of paracrine signaling in brain microvascular endothelial cells on the survival of neurons. 1955 12

Oestrogens are powerful endogenous and exogenous neuroprotective hormones in animal models of brain injury, including focal cerebral ischaemia. This protective effect has been demonstrated under a variety of different treatments and injury paradigms, such as in vivo and in vitro stroke conditions. Neuroprotection in the central nervous system by progesterone is less defined. In the present study, cultured cortical and midbrain mouse neurones and human neuroblastoma cells (SH-SY5Y) were exposed to combined glucose-serum deprivation (CGSD), which is regarded as a reliable model mimicking the effects of ischaemia in vitro. Cell viability was assayed using lactate dehydrogenase release and metabolic activity. Conditions for CGSD treatment were chosen to yield half-maximal cell death rates. The validity of CGSD in vitro was compared with permanent middle cerebral artery occlusion (MCAO) in vivo. CGSD for 4 h induced half-maximal neuronal cell death. MCAO in vivo for the same period resulted in significant neuronal loss, also suggesting the validity of CGSD as a suitable stroke-like in vitro model. Combined steroid treatment (17beta-oestradiol and progesterone) but not the application of single steroids abolished CGSD-induced cell death of cortical neurones in vitro. By contrast, no cell protection was found in midbrain neurones or neuroblastoma cells. The co-application of oestrogen (ICI 182,780) or progesterone (RU-486) receptor antagonists did not obviously counteract the protective steroid effects. This suggests the operation of nonclassical steroid mechanisms and their implication in mediation of hormonal effects. The surplus of combined protective hormonal effects might be a result of the observed influence of progesterone application on neuronal oestradiol synthesis. The data obtained in the present study clearly highlight the potential of a combined steroid treatment under toxic degenerative brain pathologies.
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PMID:Combined 17beta-oestradiol and progesterone treatment prevents neuronal cell injury in cortical but not midbrain neurones or neuroblastoma cells. 1968 48

The purpose of this research was to demonstrate the protective effects and possible mechanisms of total flavones of rhododendra (TFR) against global cerebral ischemia reperfusion injury in rats. Global cerebral ischemia/reperfusion injury was caused by four vessel occlusion (bilateral vertebral arteries and bilateral carotid arteries, 4-VO). The electroencephalographic (EEG) changes were recorded. The EEG, brain water content, levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) activity in plasma, aggregation of platelets induced by ADP, and the resting and CaCl(2)-induced increase of free intracellular calcium concentration ([Ca(2+)](i)), were also evaluated. TFR dramatically elevated EEG amplitude, reduced the brain water content and the resting cytoplasmic free calcium concentration, inhibited the increase of [Ca(2+)](i) induced by CaCl(2) and had an inhibitory effect on platelet aggregation. The LDH activity and the MDA content in plasma were also decreased. These results indicate that TFR has protective effects against cerebral injury in rats, which might be associated with its antioxidant properties, antiplatelet effects and possible inhibition of Cal(2+) influx to reduce [Ca(2+)](i).
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PMID:Protective effects of total flavones of rhododendra against global cerebral ischemia reperfusion injury. 1988 48

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