共查询到20条相似文献,搜索用时 15 毫秒
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Changlian Zhu Zhiheng Huang Jianfeng Gao Yu Zhang Xiaoyang Wang Niklas Karlsson Qian Li Birgitta Lannering Thomas Björk‐Eriksson H. Georg Kuhn Klas Blomgren 《Journal of neurochemistry》2009,111(6):1447-1456
Cranial radiotherapy is common in pediatric oncology. Our purpose was to investigate if irradiation (IR) to the immature brain would increase the susceptibility to hypoxic‐ischemic injury in adulthood. The left hemisphere of postnatal day 10 (P10) mice was irradiated with 8 Gy and subjected to hypoxia‐ischemia (HI) on P60. Brain injury, neurogenesis and inflammation were evaluated 30 days after HI. IR alone caused significant hemispheric tissue loss, or lack of growth (2.8 ± 0.42 mm3, p < 0.001). Tissue loss after HI (18.2 ± 5.8 mm3, p < 0.05) was synergistically increased if preceded by IR (32.0 ± 3.5 mm3, p < 0.05). Infarct volume (5.1 ± 1.6 mm3) nearly doubled if HI was preceded by IR (9.8 ± 1.2 mm3, p < 0.05). Pathological scoring revealed that IR aggravated hippocampal, cortical and striatal, but not thalamic, injury. Hippocampal neurogenesis decreased > 50% after IR but was unchanged by HI alone. The number of newly formed microglia was three times higher after IR + HI than after HI alone. In summary, IR to the immature brain produced long‐lasting changes, including decreased hippocampal neurogenesis, subsequently rendering the adult brain more susceptible to HI, resulting in larger infarcts, increased hemispheric tissue loss and more inflammation than in non‐irradiated brains. 相似文献
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Thi Thuy Hong Duong Belal Chami Aisling C. McMahon Genevieve M. Fong Joanne M. Dennis Saul B. Freedman Paul K. Witting 《Journal of neurochemistry》2014,130(6):733-747
Treatments to inhibit or repair neuronal cell damage sustained during focal ischemia/reperfusion injury in stroke are largely unavailable. We demonstrate that dietary supplementation with the antioxidant di‐tert‐butyl‐bisphenol (BP) before injury decreases infarction and vascular complications in experimental stroke in an animal model. We confirm that BP, a synthetic polyphenol with superior radical‐scavenging activity than vitamin E, crosses the blood–brain barrier and accumulates in rat brain. Supplementation with BP did not affect blood pressure or endogenous vitamin E levels in plasma or cerebral tissue. Pre‐treatment with BP significantly lowered lipid, protein and thiol oxidation and decreased infarct size in animals subjected to middle cerebral artery occlusion (2 h) and reperfusion (24 h) injury. This neuroprotective action was accompanied by down‐regulation of hypoxia inducible factor‐1α and glucose transporter‐1 mRNA levels, maintenance of neuronal tissue ATP concentration and inhibition of pro‐apoptotic factors that together enhanced cerebral tissue viability after injury. That pre‐treatment with BP ameliorates oxidative damage and preserves cerebral tissue during focal ischemic insult indicates that oxidative stress plays at least some causal role in promoting tissue damage in experimental stroke. The data strongly suggest that inhibition of oxidative stress through BP scavenging free radicals in vivo contributes significantly to neuroprotection.
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Platelet‐activating factor (PAF) is an important mediator of anaphylaxis and is therefore an anti‐anaphylactic drug target. We recently reported that synthetic N‐terminally biotinylated peptides (BP4‐BP29) inhibit PAF by directly interacting with PAF and its metabolite/precursor lyso‐PAF. In this study, we investigated whether the biotinylated peptides can inhibit anaphylactic reactions in vivo. In mouse models of anaphylaxis, one of the peptides, BP21, markedly and dose‐dependently inhibited hypothermia with a maximum dose–response within 30 min after administration, even at doses 20 times lesser than doses of the known PAF antagonist CV‐3988. In contrast, the anti‐hypothermic effect of BGP21, in which the Tyr‐Lys‐Asp‐Gly sequence in BP21 was modified to a Gly‐Gly‐Gly‐Gly sequence, was less than that of BP21. The alanine scanning and shuffling the amino acid residues of BP4 (Tyr‐Lys‐Asp‐Gly) demonstrated that the Tyr‐Lys‐Asp‐Gly consensus sequence is important for the inhibitory effect of the peptide on hypothermia. BP21 also suppressed vascular permeability during anaphylaxis with a maximum dose–response within 30 min of administration. In a rat model of hind paw oedema, BP21 significantly inhibited the oedema induced by PAF but not that induced by the other pro‐inflammatory mediators, such as histamine, serotonin, and bradykinin. Tryptophan fluorescence measurements showed that BP21 interacted with PAF, but not with histamine, serotonin, or bradykinin. In contrast, BGP21 did not interact with PAF. These results suggest that biotinylated peptides, especially BP21, can specifically and markedly inhibit anaphylactic reactions in vivo and that this involves direct interaction of its Tyr‐Lys‐Asp‐Gly region with PAF. Therefore, a biotinylated peptide, BP21, can be used as novel potential anti‐anaphylactic drugs targeting PAF. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
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Cortical spreading depression preconditioning mediates neuroprotection against ischemic stroke by inducing AMP‐activated protein kinase‐dependent autophagy in a rat cerebral ischemic/reperfusion injury model 下载免费PDF全文
Pingping Shen Shuai Hou Mingqin Zhu Mingming Zhao Yibing Ouyang Jiachun Feng 《Journal of neurochemistry》2017,140(5):799-813
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Effects of ischemic post‐conditioning on neuronal VEGF regulation and microglial polarization in a rat model of focal cerebral ischemia 下载免费PDF全文
Elga Esposito Kazuhide Hayakawa Bum Ju Ahn Su Jing Chan Changhong Xing Anna C. Liang Kyu‐Won Kim Ken Arai Eng H. Lo 《Journal of neurochemistry》2018,146(2):160-172
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Shibani S. Mukerji Riley N. Rainey Jamie L. Rhodes Alison K. Hall 《Journal of neurochemistry》2009,111(5):1138-1148
Focal cerebral ischemia and reperfusion initiates complex cellular and molecular interactions that lead to either cell repair or destruction. In earlier work, we found that activin A is an early gene response to cerebral ischemia and supports cortical neuron survival in vitro. In this study, the ability of exogenous activin A to attenuate injury from transient middle cerebral artery occlusion was tested in adult mice. Intracerebroventricular administration of activin A prior to middle cerebral artery occlusion reduced infarct volume apparent 1 day after experimental stroke. A single activin A administration at 6 h following ischemia/reperfusion reduced lesion volumes at 1 and 3 days and led to improved neurobehavior. Moreover, activin A treatment spared neurons within the ischemic hemisphere and led to a concomitant reduction in microglial activation. Activation of the stress-responsive kinases p38 and c- jun N-terminal kinase implicated in neuronal apoptosis after stroke was reduced following activin A treatment. Together these findings suggest that activin A promotes tissue survival after focal cerebral ischemia/reperfusion with an extended therapeutic window. 相似文献
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miR‐210 mediates vagus nerve stimulation‐induced antioxidant stress and anti‐apoptosis reactions following cerebral ischemia/reperfusion injury in rats 下载免费PDF全文
Ying Jiang Longling Li Xiaodan Tan Bin Liu Yanhong Zhang Changqing Li 《Journal of neurochemistry》2015,134(1):173-181
Vagus nerve stimulation (VNS) exerts neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury and modulates redox status, potentially through the activity of miR‐210, an important microRNA that is regulated by hypoxia‐inducible factor and Akt‐dependent pathways. The aim of this study was to determine the mechanisms of VNS‐ and miR‐210‐mediated hypoxic tolerance. Male Sprague–Dawley rats were preconditioned with a miR‐210 antagomir (A) or with an antagomir control (AC), followed by middle cerebral artery occlusion and VNS treatment. The animals were divided into eight groups: sham I/R, I/R, I/R+AC, I/R+A, sham I/R+VNS, I/R+VNS, I/R+VNS+AC, and I/R+VNS+A. Activation of the endogenous cholinergic a7 nicotinic acetylcholine receptor (a7nAchR) pathway was identified using double immunofluorescence staining. miR‐210 expression was measured by PCR. Behavioral outcomes, infarct volume, and neuronal apoptosis were observed at 24 h following reperfusion. Markers of oxidative stress were detected using ELISA. Rats treated with VNS showed increased miR‐210 expression as well as decreased apoptosis and antioxidant stress responses compared with the I/R group; these rats also showed increased p‐Akt protein expression and significantly decreased levels of cleaved caspase 3 in the ischemic penumbra, as measured by western blot and immunofluorescence analyses, respectively. Strikingly, the beneficial effects of VNS were attenuated following miR‐210 knockdown. In conclusion, our results indicate that miR‐210 is a potential mediator of VNS‐induced neuroprotection against I/R injury. Our study highlights the neuroprotective potential of VNS, which, to date, has been largely unexplored.
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MXRA5 is a TGF‐β1‐regulated human protein with anti‐inflammatory and anti‐fibrotic properties 下载免费PDF全文
Jonay Poveda Ana B. Sanz Beatriz Fernandez‐Fernandez Susana Carrasco Marta Ruiz‐Ortega Pablo Cannata‐Ortiz Alberto Ortiz Maria D. Sanchez‐Niño 《Journal of cellular and molecular medicine》2017,21(1):154-164
Current therapy for chronic kidney disease (CKD) is unsatisfactory because of an insufficient understanding of its pathogenesis. Matrix remodelling‐associated protein 5 (MXRA5, adlican) is a human protein of unknown function with high kidney tissue expression, not present in rodents. Given the increased expression of MXRA5 in injured tissues, including the kidneys, we have suggested that MXRA5 may modulate kidney injury. MXRA5 immunoreactivity was observed in tubular cells in human renal biopsies and in urine from CKD patients. We then explored factors regulating MXRA5 expression and MXRA5 function in cultured human proximal tubular epithelial cells and explored MXRA5 expression in kidney cancer cells and kidney tissue. The fibrogenic cytokine transforming growth factor‐β1 (TGFβ1) up‐regulated MXRA5 mRNA and protein expression. TGFβ1‐induced MXRA5 up‐regulation was prevented by either interference with TGFβ1 activation of the TGFβ receptor 1 (TGFBR1, ALK5) or by the vitamin D receptor agonist paricalcitol. By contrast, the pro‐inflammatory cytokine TWEAK did not modulate MXRA5 expression. MXRA5 siRNA‐induced down‐regulation of constitutive MXRA5 expression resulted in higher TWEAK‐induced expression of chemokines. In addition, MXRA5 down‐regulation resulted in a magnified expression of genes encoding extracellular matrix proteins in response to TGFβ1. Furthermore, in clear cell renal cancer, von Hippel–Lindau (VHL) regulated MXRA5 expression. In conclusion, MXRA5 is a TGFβ1‐ and VHL‐regulated protein and, for the first time, we identify MXRA5 functions as an anti‐inflammatory and anti‐fibrotic molecule. This information may yield clues to design novel therapeutic strategies in diseases characterized by inflammation and fibrosis. 相似文献
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The non‐peptidic δ‐opioid receptor agonist Tan‐67 mediates neuroprotection post‐ischemically and is associated with altered amyloid precursor protein expression,maturation and processing in mice 下载免费PDF全文
Jia‐Wei Min Yanying Liu David Wang Fangfang Qiao Hongmin Wang 《Journal of neurochemistry》2018,144(3):336-347
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Jae‐Hyun Lee Jung‐Ho Sohn Su Yeon Ryu Chein‐Soo Hong Jung‐Won Park 《Journal of cellular and molecular medicine》2013,17(10):1271-1281
Asthma is a chronic inflammatory disease induced by Type 2 helper T cells and eosinophils. Vascular cell adhesion molecule‐1 (VCAM‐1) has been implicated in recruiting eosinophils and lymphocytes to pathological sites in asthma as a regulatory receptor. Accordingly, monoclonal antibody (mAb) against VCAM‐1 may attenuate allergic inflammation and pathophysiological features of asthma. We attempted to evaluate whether a recently developed human anti‐VCAM‐1 mAb can inhibit the pathophysiological features of asthma in a murine asthma model induced by ovalbumin (OVA). Leucocyte adhesion inhibition assay was performed to evaluate the in vitro blocking activity of human anti‐VCAM‐1 mAb. OVA‐sensitized BALB/c mice were treated with human anti‐VCAM‐1 mAb or isotype control Ab before intranasal OVA challenge. We evaluated airway hyperresponsiveness (AHR) and bronchoalveolar lavage fluid analysis, measured inflammatory cytokines and examined histopathological features. The human anti‐VCAM‐1 mAb bound to human and mouse VCAM‐1 molecules and inhibited adhesion of human leucocytes in vitro. AHR and inflammatory cell counts in bronchoalveolar lavage fluid were reduced in mice treated with human anti‐VCAM‐1 mAb as compared with a control Ab. The levels of interleukin (IL)‐5 and IL‐13, as well as transforming growth factor‐β, in lung tissue were decreased in treated mice. Human anti‐VCAM‐1 mAb reduced goblet cell hyperplasia and peribronchial fibrosis. In vivo VCAM‐1 expression decreased in the treated group. In conclusion, human anti‐VCAM‐1 mAb attenuated allergic inflammation and the pathophysiological features of asthma in OVA‐induced murine asthma model. The results suggested that human anti‐VCAM‐1 mAb could potentially be used as an additional anti‐asthma therapeutic medicine. 相似文献
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Baicalin effects on rats with spinal cord injury by anti‐inflammatory and regulating the serum metabolic disorder 下载免费PDF全文
Shufeng Kang Shizhao Liu Hongzhu Li Dapeng Wang Xiangbei Qi 《Journal of cellular biochemistry》2018,119(9):7767-7779
Baicalin had neuroprotective effects on inhibiting neuronal cell apoptosis induced by spinal cord ischemic injury. This study aimed to explore the protective effects of Baicalin on rats with spinal cord injury (SCI) and its mechanism of action. The recovery of spinal cord nerve function in rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) score and the combine behavioral score (CBS). The expressions of cytokines tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 were detected by the enzyme‐linked immunosorbent assay method. Expressions of inflammation‐related proteins were detected by Western blot. Multivariate statistical analysis was performed for serum metabolites. The BBB and CBS score results showed that Baicalin had a certain improvement on rats with SCI. SCI symptoms were significantly improved in low‐dose and high‐dose groups. The levels of TNF‐α, IL‐1β, and IL‐6 in the SCI group were significantly increased. The expressions of NF‐κB p65, NF‐κB p50, p‐IκBα, and IKKα in the SCI group showed the opposite trend compared with the low‐dose and high‐dose groups. Compared with the sham group, glutamine, levels of 3‐OH‐butyrate, N‐acetylaspartate, and glutathione were significantly reduced, and the levels of glutamate and betaine were significantly increased in the SCI group. When Baicalin was administered, the contents of glutamine synthase (GS) and glutaminase (GLS) were significantly reduced, indicating that Baicalin had the effect of improving GS and GLS. Baicalin has protective effects on improving SCI and lower extremity motor function, has a significant anti‐inflammatory effect, and regulates the serum metabolic disorder caused by SCI in rats. 相似文献
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P. Hemachandra Reddy Maria Manczak Wei Zhao Kazuhiro Nakamura Christopher Bebbington Geoffrey Yarranton Peizhong Mao 《Journal of neurochemistry》2009,111(6):1514-1528
The objective of our study was to determine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) activity in the brain following GM‐CSF induction. We injected recombinant mouse GM‐CSF into the brains of 8‐month‐old C57BL6 mice via intracerebroventricular injections and studied the activities of microglia, astrocytes, and neurons. We also sought to determine whether an anti‐GM‐CSF antibody could suppress endogenous microglial activity in the C57BL6 mice and could also suppress microglial activity induced by the recombinant mouse GM‐CSF in another group of C57BL6 mice. Using quantitative real‐time RT‐PCR, we assessed microglial, astrocytic, and neuronal activity by measuring mRNA expression of pro‐inflammatory cytokines, GFAP, and the neuronal marker NeuN in the cerebral cortex tissues from C57BL6 mice. We performed immunoblotting and immunohistochemistry of activated microglia in different regions of the brains from control (phosphate‐buffered saline‐injected C57BL6 mice) and experimental mice (recombinant GM‐CSF‐injected C57BL6 mice, GM‐CSF antibody‐injected C57BL6 mice, and recombinant mouse GM‐CSF plus anti‐GM‐CSF antibody‐injected C57BL6 mice). We found increased mRNA expression of CD40 (9.75‐fold), tumor necrosis factor‐alpha (2.1‐fold), CD45 (1.73‐fold), and CD11c (1.70‐fold) in the cerebral cortex of C57BL6 mice that were induced with recombinant GM‐CSF, compared with control mice. Further, the anti‐GM‐CSF antibody suppressed microglia in mice that were induced with recombinant GM‐CSF. Our immunoblotting and immunohistochemistry findings of GM‐CSF‐associated cytokines in C57BL6 mice induced with recombinant GM‐CSF, in C57BL6 mice injected with the anti‐GM‐CSF antibody, and in C57BL6 mice injected with recombinant mouse GM‐CSF plus anti‐GM‐CSF antibody concurred with our real‐time RT‐PCR findings. These findings suggest that GM‐CSF is critical for microglial activation and that anti‐GM‐CSF antibody suppresses microglial activity in the CNS. The findings from this study may have implications for anti‐inflammatory effects of Alzheimer’s disease and experimental autoimmune encephalomyelitis mice (a multiple sclerosis mouse model). 相似文献
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Conventional protein kinase Cβ‐mediated phosphorylation inhibits collapsin response‐mediated protein 2 proteolysis and alleviates ischemic injury in cultured cortical neurons and ischemic stroke‐induced mice 下载免费PDF全文
Xuan Yang Xinxin Zhang Yun Li Song Han David W. Howells Shujuan Li Junfa Li 《Journal of neurochemistry》2016,137(3):446-459