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Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
October 18, 2016: International Immunopharmacology
Yuji Kaneko, Colleen Pappas, Naoki Tajiri, Cesar V Borlongan
Oxytocin protects against ischemia-induced inflammation and oxidative stress, and is associated with GABA (γ-aminobutyric acid, an inhibitory neurotransmitter) signaling transduction in neurons. However, the molecular mechanism by which oxytocin affords neuroprotection, especially the interaction between oxytocin receptor and GABAA receptor (GABAAR), remains to be elucidated. Primary rat neural cells were exposed to oxytocin before induction of experimental acute stroke model via oxygen-glucose deprivation-reperfusion (OGD/R) injury...
October 21, 2016: Scientific Reports
Yang Li, Jian Li, Zhiwen Hou, Yang Yu, Bo Yu
The primary physiological function of Krüppel-like zinc-finger transcription factor (KLF5) is the regulation of cardiovascular remodeling. Vascular remodeling is closely related to the amelioration of various ischemic diseases. However, the underlying correlation of KLF5 and ischemia is not clear. In this study, we aim to investigate the role of KLF5 in myocardial ischemia reperfusion (IR) injury and the potential mechanisms involved. Cultured H9C2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/Rep) to mimic myocardial IR injury in vivo...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shuang Chen, Jie Yan, Hai-Xiao Deng, Ling-Ling Long, Yong-Jun Hu, Mi Wang, Lei Shang, Dan Chen, Ju-Fang Huang, Kun Xiong
The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Yong Li, Xu Wang, Jie Yang, Xilei Xie, Mengmeng Li, Jinye Niu, Lili Tong, Bo Tang
Carbon monoxide (CO), a crucial gas message molecule, plays an important role in the regulation of physiological and pathological process. Hypoxia-induced CO is involved in modulating various cellular activities, including signal transduction, proliferation, and apoptosis. However, tracking CO fluctuation in the hypoxic cells is still a challenge due to lack of straight forward, visualized and non-invasive tools. In this work, based on metal palladium-catalyzed reaction, we present the rational design, synthesis and biological utility of an azobenzene-cyclopalladium-based fluorescent probe, ACP-2, for CO monitoring...
October 17, 2016: Analytical Chemistry
D K Rieger, E Navarro, I Buendia, E Parada, L González-Lafuente, R Leon, A P Costa, I A Heinrich, K S Nascimento, B S Cavada, M G Lopez, J Egea, R B Leal
Lectins are proteins that bind cellular glycans and can modulate various neuronal functions. We have evaluated the neuroprotective effect of ConBr, a lectin purified from the seeds of Canavalia brasiliensis in a model of rat organotypic hippocampal cultures (OHCs) exposed to oxygen and glucose deprivation (OGD). OGD for 15 min followed by 24 h re-oxygenation significantly increased cell death, caused mitochondrial depolarization and increased reactive oxygen species (ROS) in CA1 region of OHCs. ConBr (0.1 μg/mL) added during the re-oxygenation period counteracted cell death, mitochondrial depolarization and overproduction of ROS induced by OGD...
October 17, 2016: Neurochemical Research
Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
Shyanne Page, Alli Munsell, Abraham J Al-Ahmad
BACKGROUND: Cerebral hypoxia/ischemia (H/I) is an important stress factor involved in the disruption of the blood-brain barrier (BBB) following stroke injury, yet the cellular and molecular mechanisms on how the human BBB responds to such injury remains unclear. In this study, we investigated the cellular response of the human BBB to chemical and environmental H/I in vitro. METHODS: In this study, we used immortalized hCMEC/D3 and IMR90 stem-cell derived human brain microvascular endothelial cell lines (IMR90-derived BMECs)...
October 11, 2016: Fluids and Barriers of the CNS
Jing Qiu, Zhongjun Yan, Kai Tao, Yansong Li, Yuqian Li, Jingchen Li, Yushu Dong, Dayun Feng, Huisheng Chen
BACKGROUND: Astrocyte-mediated neuroinflammation plays a critical role in ischemic stroke-induced secondary cerebral injury. Previous studies have suggested that the dopamine D2 receptor (DRD2) acts as a key target in regulating the neuroinflammatory response. However, the underlying molecular mechanisms are still unknown, and effective DRD2 agonists are lacking. In the present study, we examined the anti-inflammatory and neuroprotective effects of sinomenine (Sino), a monomeric compound with potential immunoregulatory properties in nervous system...
October 10, 2016: Journal of Neuroinflammation
Bin Zhang, Ning Yang, Shao-Peng Lin, Feng Zhang
Cerebral infarction (CI) is a common clinical cerebrovascular disease, and to explore the pathophysiological mechanisms and seek effective treatment means are the hotspot and difficult point in medical research nowadays. Numerous studies have confirmed that uric acid plays an important role in CI, but the mechanism has not yet been clarified. When treating HT22 and BV-2 cells with different concentrations of uric acid, uric acid below 450 μM does not have significant effect on cell viability, but uric acid more than 500 μM can significantly inhibit cell viability...
October 5, 2016: Cellular and Molecular Neurobiology
Li Su, Hongli Du, Xin Dong, Xiuhua Zhang, Ziyang Lou
Raf-1 kinase inhibitory protein (RKIP) is a critical molecule for cellular responses to stimuli. In this study, we investigated whether RKIP is responsible for neural cell apoptosis induced by oxygen-glucose deprivation (OGD) and explored the role of NF-κB and ERK pathways regulated by RKIP under OGD stimuli. RKIP was overexpressed or knocked down using lentivirus in PC12 cells, which were then challenged by OGD. RKIP overexpression significantly increased the cell viability of OGD cells, and attenuated apoptosis, cell cycle arrest, and reactive oxygen species generation...
September 2016: Journal of Clinical Biochemistry and Nutrition
Jing Yu Ng, Dedrick Kok Hong Chan, Ker Kan Tan
BACKGROUND: The use of fecal immunochemical test (FIT) in the screening for colorectal cancer is long established. However, more than 50 % of patients with positive FITs have a negative colonoscopy. The role of a subsequent oesophago-gastro-duodenoscopy (OGD) is debatable. The aim of this study is to evaluate the yield of OGD in patients with positive FITs. METHODOLOGY: A retrospective review of patients who underwent colonoscopy for a positive FIT between Jan...
September 30, 2016: International Journal of Colorectal Disease
Qin Wang, Jiangwen Yin, Sheng Wang, Di Cui, Hong Lin, Mingyue Ge, Zhigang Dai, Liping Xie, Junqiang Si, Ketao Ma, Li Li, Lei Zhao
BACKGROUND: Isoflurane postconditioning (ISPOC) plays a neuroprotection role in the brain. Previous studies confirmed that isoflurane postconditioning can provide better protection than preconditioning in acute hypoxic-ischemic brain damage, such as acute craniocerebral trauma and ischemic stroke. Numerous studies have reported that activin A can protect rat's brain from cell injury. However, whether activin A and its downstream ERK1/2 were involved in isoflurane postconditioning-induced neuroprotection is unknown...
September 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Akihiro Watanabe, Tsutomu Sasaki, Toshiro Yukami, Hideaki Kanki, Manabu Sakaguchi, Takemori Hiroshi, Kazuo Kitagawa, Hideki Mochizuki
There are no effective neuroprotectant drugs for acute cerebral ischemia. Serine racemase (SR) synthesizes d-serine, which is involved in N-methyl-d-aspartate (NMDA) receptor-induced neurotoxicity. Recently, SR deletion was reported to protect against focal cerebral ischemia. However, regulatory mechanisms controlling SR-activity in the neurovascular unit (NVU) during cerebral ischemia remain to be clarified. We investigated the effects of SR inhibition on neurovascular protection after ischemia. The SR inhibitor phenazine methosulfate (PMS) alleviated neuronal damage in an ex vivo ischemic model (oxygen glucose deprivation [OGD]) using primary neuronal cultures, and in an in vivo mouse model of ischemia (middle cerebral artery occlusion [MCAO])...
September 28, 2016: Neuroscience
Li Lv, Qian Lu, Fangyu Shao, Weiping Li, Qin Zhou, Jihong Wang, Qingwei Li
rLj-RGD3 is a 14.5 kDa recombinant protein with 3 RGD (Arg-Gly-Asp) motifs from the salivary gland secretions of Lampetra japonica, which is a histidine-rich and arginine-rich protein. Previous reports indicated that rLj-RGD3 has typical functions of RGD-toxin protein, such as platelet aggregation suppression tumour metastasis and angiogenesis inhibition. Because histidine and arginine have cerebral ischemia-reperfusion and neuroprotective functions, we investigated whether rLj-RGD3 has such activities and studied the mechanism...
2016: BioMed Research International
Hong-Wei Li, Bin Zhou, Hai-Hong Zhang
OBJECTIVE: To explore the molecular mechanism responsible for apoptosis of PC-12 neuronal cells induced by oxygen-glucose deprivation (OGD). METHODS: PC12 cells were exposed to OGD for 24 h to simulate ischemia-reperfusion injury. Flow cytometry was employed detect the cell apoptosis, and the expresions of TRPM8, UCP4, cAMP and PKA in the exposed cells were detected with RT-PCR and Western blotting. The changes in the expressions of Bax, Bcl-2, cAMP, PKA and UCP4 proteins were detected in the exposed cells in resposne to inhibition of TRPM8 and cAMP-PKA signal or over-expression of UCP4...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Hongqi Xin, Fengjie Wang, Yanfeng Li, Qing-E Lu, Wing Lee Cheung, Yi Zhang, Zheng Gang Zhang, Michael Chopp
We previously demonstrated that multipotent mesenchymal stromal cells (MSCs) with overexpressed microRNA 133b (miR-133b) significantly improve functional recovery in rats subjected to middle cerebral artery occlusion (MCAO) compared with naive MSCs, and that exosomes generated from naive MSCs mediate the therapeutic benefits of MSC therapy for stroke. Here, we investigated whether exosomes isolated from miR-133b(-)overexpressed MSCs (Ex-miR-133b(+)) exert amplified therapeutic effects. Rats subjected to 2 hours (h) of MCAO were intra-arterially injected with Ex-miR-133b(+), exosomes from MSCs infected by blank vector (Ex-Con), or phosphate-buffered solution (PBS), and were sacrificed 28 days post MCAO...
September 26, 2016: Cell Transplantation
Jue Wang, Dong Han, Miao Sun, Juan Feng
Cerebral ischemic postconditioning (IPOC) has been demonstrated to be neuroprotective against cerebral ischemia reperfusion injury. The present study aimed to determine whether IPOC could inhibit autophagy and high mobility group box 1 (HMGB1) release in a PC12 cell oxygen glucose deprivation/reperfusion (OGD/R) model. An 8 h OGD and 24 h reperfusion cellular model was developed to mimic cerebral ischemia reperfusion injury, with 3 cycles of 10 min OGD/5 min reperfusion treatment to imitate IPOC. Cell viability was determined to demonstrate the efficiency of OGD/R, IPOC and autophagy activator, rapamycin (RAP), treatment...
September 19, 2016: Molecular Medicine Reports
Wenjie Wei, Zhiyuan Yu, Minjie Xie, Wei Wang, Xiang Luo
Growing evidence has revealed that brain pericytes are multifunctional and contribute to the pathogenesis of a number of neurological disorders. However, the role of pericytes in cerebral ischemia, and especially the pathophysiological alterations in pericytes, remains unclear. In the present study, our aim was to determine whether the proliferation of pericytes is affected by cerebral ischemia and, if so, to identify the underlying mechanism(s). Cultured brain pericytes subjected to oxygen-glucose deprivation (OGD) were used as our model of cerebral ischemia; the protein expression levels of cyclin D1, cyclin E, cdk4, and cyclin B1 were determined by Western blot analysis, and cell cycle analysis was assessed by flow cytometry...
September 24, 2016: Journal of Molecular Neuroscience: MN
Hye-Seon Jung, Si-Yeon Jeong, Jiwon Yang, So-Dam Kim, Baojin Zhang, Hyun Seung Yoo, Sun U Song, Myung-Shin Jeon, Yun Seon Song
Bone marrow-derived mesenchymal stem cells (MSCs) are used in stroke treatment despite the poor understanding of its mode of action. The immune suppressive and anti-inflammatory properties of MSCs possibly play important roles in regulating neuroinflammation after stroke. We investigated whether MSCs reduce the inflammatory complement component 3 (C3) levels, thus, providing neuroprotection during stroke. Mice were subjected to transient focal cerebral ischemia (tFCI), after which MSCs were intravenously injected...
October 28, 2016: Neuroscience Letters
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