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)

Aurintricarboxylic acid (ATA) has been reported to protect PC12 cells and cultured neuronal cells from serum starvation-induced cell death, and hippocampal neurons from N-methyl D-aspartate- or ischemia-induced cell death in vivo. We have found that ATA activated tyrosine phosphorylation cascade in PC12 cells as growth factors. Here, we report that ATA prevents cell death under serum starvation and induces tyrosine phosphorylation also in human neuroblastoma SH-SY5Y cells. Furthermore, it was found that erbB4, a member of epidermal growth factor receptor family, is tyrosine-phosphorylated in response to ATA. Both, erbB4 and its ligand, neu differentiation factor (NDF)/ heregulin family, have been reported to be expressed abundantly in nervous system. Thus, tyrosine phosphorylation of erbB4 might explain the neuro-protective activity of ATA.
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PMID:Tyrosine phosphorylation of ErbB4 is stimulated by aurintricarboxylic acid in human neuroblastoma SH-SY5Y cells. 901 63

Neuregulin-1 (NRG-1) is expressed throughout the immature and adult central nervous system and it has been demonstrated to influence the migration of a variety of cell types in developing brain. Elevated levels of NRG-1 transcript are found in the adult brain after injury, leading to the suggestion that NRG-1 is involved in the physiological response to neuronal injury. Here, we report our findings that rats pre-treated with NRG-1 protein, undergoing cerebral ischemia 30 min later, had increased motor performance and less cerebral infarction than untreated rats. In the cortex of NRG-1 treated rats, ischemia induced a decrease in caspase-3 immunoreactivity and a reduction in the density of cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end-labeling. Improvement in behavioral assays was also found in animals treated with NRG-1. Pre-treatment with NRG-1 did not alter cerebral blood flow or other physiological parameters. NRG-1 reduced ischemia/reperfusion injury, indicating that it may act as an endogenous neuroprotective factor against stroke. Therefore, NRG-1 may represent a target for the development of new treatments for stroke.
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PMID:Neuregulin-1 reduces ischemia-induced brain damage in rats. 1521 47

Recent work from our laboratory demonstrated that the expression neuregulin-1 in neurons was induced in the ischemic penumbra by focal stroke in the rat. Here, we show that a single intravascular injection of neuregulin-1beta (approximately 2.5 ng/kg) reduced cortical infarct volume by >98% when given immediately before middle cereral artery occlusion. Subcortical infarct volume was reduced by approximately 40%. Analysis of DNA fragmentation in brain tissues indicated that neuregulin-1 blocked apoptosis in cortical neurons in the penumbra. Neuregulin-1 prevented macrophage/microglial infiltration and astrocytic activation following focal ischemia. The neuroprotective effect of neuregulin-1 was also associated with a suppression of interleukin-1beta mRNA levels. These data suggest that neuregulin-1 protects neurons from delayed, ischemia-induced apoptotic cell death in the cortex by inhibiting pro-inflammatory responses. Neuregulins represent a novel, potent neuroprotective strategy that has potential therapeutic value in treating individuals after acute ischemic stroke.
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PMID:Neuregulin-1 is neuroprotective and attenuates inflammatory responses induced by ischemic stroke. 1532 49

We have previously demonstrated that neuregulin-1 (NRG-1) is upregulated and is neuroprotective in ischemic brain injury, however the expression and localization of its receptors during ischemia has not been investigated. Therefore, we used a rat middle cerebral artery occlusion (MCAO) model to examine the distribution of erbB receptors following ischemic stroke. Like neuregulin-1, we observed a dramatic induction of erbB4 in the peri-infarct regions of the ipsilateral cortex 24 h following MCAO. Using Fluoro-Jade B (FJB) staining as a marker of neurodegeneration, erbB4 was upregulated in FJB-positive cells, suggesting that erbB receptors are induced in injured neurons. The increase in erbB receptors was seen in neurons and a subpopulation of macrophages/microglia. There was no erbB co-localization with GFAP-positive astrocytes. These results demonstrate that erbB receptors are upregulated in neurons and macrophages/microglia following ischemic stroke and may be involved in neuroprotection and repair.
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PMID:Upregulation of erbB receptors in rat brain after middle cerebral arterial occlusion. 1569 57

Neuregulins are a family of growth factors with potent neuroprotective properties. We recently demonstrated that neuregulin-1 blocked delayed neuronal death following focal ischemic stroke in the rat. Focal ischemia results in the release of pro-inflammatory cytokines that produce profound changes in gene expression and contribute to cell death associated with stroke. Inflammatory and stress mediators are involved in the pathogenesis of focal ischemic brain damage. We examined whether neuregulin-1 can influence inflammatory and stress gene expression in the rat brain following transient middle cerebral artery occlusion (MCAO). In this study, we compared gene expression profiles in animals treated with neuregulin-1beta (NRG-1) or vehicle followed by MCAO. We used the Affymetrix GeneChip system to analyze gene expression in focal ischemia of the rat brain. Several inflammatory and stress genes were significantly induced following MCAO compared to sham controls including heat shock protein-70 (HSP70), interleukin-1beta, and macrophage chemotattractant protein-1 (JE/MCP-1). Treatment with NRG-1 attenuated the expression of many of these genes by 50% or more. In vitro studies demonstrated that NRG-1 suppressed inflammatory gene expression in activated macrophages. NRG-1 also prevented neuronal death induced by oxygen-glucose deprivation in a rat neuroblastoma cell line, suggesting that NRG-1 may have both direct and indirect neuroprotective capacity. These results demonstrate that NRG-1 can regulate inflammatory and stress gene expression and may give new insight to the molecular mechanisms involved in the neuroprotective role of neuregulins in stroke.
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PMID:Neuroprotection by neuregulin-1 following focal stroke is associated with the attenuation of ischemia-induced pro-inflammatory and stress gene expression. 1602 88

Epidemiologic studies demonstrate significant environmental impact of maternal viral infection and obstetric complications on the risk of schizophrenia and indicate their detrimental influences on brain development in this disorder. Based on these findings, animal models for schizophrenia have been established using double stranded RNA, bacterial lipopolysaccharides, hippocampal lesion, or prenatal/perinatal ischemia. Key molecules regulating such immune/inflammatory reactions are cytokines, which are also involved in brain development, regulating dopaminergic and GABAergic differentiation, and synaptic maturation. Specific members of the cytokine family, such as interleukin-1, epidermal growth factor, and neuregulin-1, are induced after infection and brain injury; therefore, certain cytokines are postulated to have a central role in the neurodevelopmental defects of schizophrenia. Recently, to test this hypothesis, a variety of cytokines were administered to rodent pups. Cytokines administered in the periphery penetrated the immature blood-brain barrier and perturbed phenotypic neural development. Among the many cytokines examined, epidermal growth factor (or potentially other ErbB1 ligands) and interleukin-1 specifically induced the most severe and persistent behavioral and cognitive abnormalities, most of which were ameliorated by antipsychotics. These animal experiments illustrate that, during early development, these cytokine activities in the periphery perturbs normal brain development and impairs later psychobehavioral and/or cognitive traits. The neurodevelopmental and behavioral consequences of prenatal/perinatal cytokine activity are compared with those of other schizophrenia models and cytokine interactions with genes are also discussed in this review.
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PMID:Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines. 1683 94

Neuregulin-1 (NRG-1) is a growth factor with potent neuroprotective capacity in ischemic stroke. We recently showed that NRG-1 reduced neuronal death following transient middle cerebral artery occlusion (tMCAO) by up to 90% with an extended therapeutic window. Here, we examined the neuroprotective potential of NRG-1 using a permanent MCAO ischemia (pMCAO) rat model. NRG-1 reduced infarction in pMCAO by 50% when administered prior to ischemia. We previously demonstrated using gene expression profiling that pMCAO was associated with an exaggerated excitotoxicity response compared to tMCAO. Therefore, we examined whether co-treatment with an inhibitor of excitotoxicity would augment the effect of NRG-1 following pMCAO. Both NRG-1 and the N-methyl-D-aspartate (NMDA) antagonist MK-801 similarly reduced infarct size following pMCAO. However, combination treatment with both NRG-1 and MK-801 resulted in greater neuroprotection than either compound alone, including a 75% reduction in cortical infarction compared to control. Consistent with these findings, NRG-1 reduced neuronal death using an in vitro ischemia model and this effect was augmented by MK-801. These results demonstrate the efficacy of NRG-1 in pMCAO rat focal ischemia model. Our findings further indicate the potential clinically relevance of NRG-1 alone or as a combination strategy for treating ischemic stroke.
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PMID:Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia. 1796 19

We previously showed that neuregulin-1 (NRG-1) protected neurons from death in vivo following focal ischemia. The goal of this study was to develop an in vitro rat ischemia model to examine the cellular and molecular mechanisms involved in the neuroprotective effects of NRG-1 on ischemia-induced neuronal death. Rat B-35 neuroblastoma cells differentiated by serum withdrawal, developed enhanced neuronal characteristics including, neurite extension and upregulation of neuronal markers of differentiation. When B35 neurons were subjected to oxygen glucose deprivation (OGD)/reoxygenation or glutamate, widespread neuronal death was seen after both treatments. Treatment with NRG-1 immediately after OGD significantly increased neuronal survival. NRG-1 administration also resulted in a significant decrease in annexin V, an early marker of apoptosis. However, the neurotoxic actions of glutamate were unaffected by NRG-1. The neuroprotective effects of NRG-1 were prevented by an inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. These results provide a new model to gain insight into the mechanisms employed by NRG-1 to protect neurons from ischemic brain injury.
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PMID:Neuroprotective effects of neuregulin-1 on B35 neuronal cells following ischemia. 1841 Sep 12

The aim is to investigate the effect of neuregulin-1beta (NRG-1beta) on the neuronal apoptosis and the expressions of signal transducer and activator of transcription (STAT3) and glial fibrillary acidic protein (GFAP) in rats following cerebral ischemia/reperfusion. The animal models of middle cerebral artery occlusion/reperfusion (MCAO/R) were established by an intraluminal filament method from left external-internal carotid artery in 100 cases of adult healthy male Wister rats. NRG-1beta was administered from the internal carotid artery (ICA) into MCA in the treatment group. The neuronal apoptosis was detected by terminal deoxynucleotidyl transference-mediated biotinylated deoxyuridine triphosphate nick-end labeling technique. The expression alternations of STAT3 and GFAP proteins were determined by fluorescent labeling analysis and Western blotting assay. Ischemic cerebral injury could induce neuronal apoptosis. Furthermore, with the duration of ischemia, the amount of apoptotic cells increased in the control group. These apoptotic cells distributed in various brain regions, especially the cortex, striatum, and hippocampus, while only a small amount of apoptotic cells could be observed in the treatment group, and there were significant differences compared with that in the control group (P < 0.01). The expressions of STAT3 and GFAP proteins in brain tissue gradually increased in the control group with the duration of ischemia. And NRG-1beta could elevate the expressional level of STAT3 and GFAP proteins in contrast to the control group (P < 0.05). NRG-1beta may play a neuroprotective role in cerebral ischemic insult by activating JAK/STAT signal transduction pathway, promoting the astrocyte gumnosis and regulating the anti-apoptosis mechanism in neurocytes.
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PMID:Effect of neuregulin on apoptosis and expressions of STAT3 and GFAP in rats following cerebral ischemic reperfusion. 1863 37

It has been demonstrated that neuregulin-1beta (NRG-1beta) plays a neuroprotective role in cerebral ischemic injury, however, its defined mechanisms and the perfect treatment window are still elusive. Therefore, we established the animal model of MCAO/R to evaluate cerebral damage. As a result, neurological deficit scores were increased, and a small infarction focus could be seen in ischemic cortex in the control group at ischemic 0.5h/reperfusion 24h. With the duration of ischemia time, deficit scores and infarction sizes obviously elevated in the control group. A large number of positive-apoptotic cells were widespread in the ischemic cortex. Simultaneously, the expression of AQP-4 mRNA and its protein increased. NRG-1beta significantly improved neurological function, decreased the infarction volume, and elevated the expression levels of AQP-4 compared with that in the control group. The therapeutic effect of NRG-1beta was notable, especially at the ischemic 1.0h. These results demonstrate that NRG-1beta might play a neuroprotective effect on cerebral ischemia and reperfusion by inhibiting mitochondrial apoptosis pathway and regulating the activation of AQP-4. The perfect treatment window is at ischemic 1.0h after MCAO.
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PMID:Neuregulin attenuated cerebral ischemia-Creperfusion injury via inhibiting apoptosis and upregulating aquaporin-4. 1868 Jul 85


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