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Stroke reperfusion injury

Yanhua Qin, Weiming Hu, Yang Yang, Zhiying Hu, Weiyun Li, Marong Fang
Aberrant production of nitric oxide following inducible nitric oxide synthase (iNOS) expression has been implicated in cell death and contributes to ischemic brain injury. Tetrahydrobiopterin (BH4) is an essential cofactor of NOS activity. Herein, we evaluated antiapoptotic and anti-inflammatory effects of diamino-6-hydroxypyrimidine (DAHP), a guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1) inhibitor on focal cerebral ischemia-reperfusion injury by middle cerebral artery occlusion and reperfusion (MCAO) and investigated the underlying mechanism...
2018: Behavioural Neurology
John O Orgah, Jiahui Yu, Tiechan Zhao, Lingyan Wang, Mingzhu Yang, Yan Zhang, Guanwei Fan, Yan Zhu
Ischemic brain injury impacts cardiac dysfunction depending on the part of the brain affected, with a manifestation of irregular blood pressure, arrhythmia, and heart failure. Generally called brain-heart syndrome in traditional Chinese medicine, few mechanistic understanding and treatment options are available at present. We hypothesize that considering the established efficacy for both ischemic stroke and myocardial infarction (MI), Danhong injection (DHI), a multicomponent Chinese patent medicine, may have a dual pharmacological potential for treating the brain-heart syndrome caused by cerebral ischemic stroke through its multi-targeted mechanisms...
2018: Frontiers in Pharmacology
Anil Kumar Rana, Damanpreet Singh
Cerebral stroke is a leading cause of early death and physical disability in adults throughout the world. Oxidative stress and inflammation plays an important role in the pathological process associated with the stroke. The available reperfusion therapy itself enhances the oxidative stress by overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) from the neurons, as well as non-neuronal cells, thus further worsens the condition. Excessive ROS and RNS production contributes to the brain injury during or after the stroke by activating inflammatory processes...
July 6, 2018: Neuropharmacology
Nan Zhang, Hongyi Zhu, Song Han, Leiming Sui, Junfa Li
Conventional protein kinase C (cPKC)γ and synapsin Ia/b have been implicated in the development of ischemic stroke, but their relationships and functions are unclear. In the present study, the oxygen-glucose deprivation (OGD)-induced ischemic insult in primary cultured cortical neurons in vitro and middle cerebral artery occlusion (MCAO)-induced ischemic stroke model in vivo were used to elucidate the function of cPKCγ and its modulation on synapsin Ia/b phosphorylation in ischemic stroke. We found that cPKCγ knockout significantly increased the infarct volume of mice after 1 h MCAO/72 h reperfusion by using triphenyltetrazolium chloride (TTC) staining...
July 14, 2018: Brain Research Bulletin
Pengfei Xu, Qian Liu, Yi Xie, Xiaolei Shi, Yunzi Li, Mengna Peng, Hongquan Quo, Rui Sun, Juanji Li, Ye Hong, Xinfeng Liu, Gelin Xu
Cellular oxidative stress plays a vital role in the pathological process of neural damage in cerebral ischemia/reperfusion (I/R). The breast cancer susceptibility protein 1 (BRCA1), a tumor suppressor, can modulate cellular antioxidant response and DNA repair. Yet the role of BRCA1 in cerebral I/R injury has not been explored. In this study, we observed that BRCA1 was mainly expressed in neurons and was up-regulated in response to I/R insult. Overexpression of BRCA1 attenuated reactive oxygen species production and lipid peroxidation...
July 7, 2018: Redox Biology
Jun Yang, Jiagui Huang, Changbo Shen, Wei Cheng, Pingping Yu, Li Wang, Fanren Tang, Shuang Guo, Qin Yang, John Zhang
Recent studies have indicated that resveratrol has protective effects against cerebral ischemia/reperfusion injury. However, the best therapeutic time for resveratrol treatment after acute ischemic stroke remains unknown. We aim to investigate whether resveratrol, administrated at different times after neuronal oxygen and glucose deprivation/reoxygenation (OGD/R) reduced neuronal injury in vitro. There were six experimental groups: normal, model, resveratrol pretreatment, resveratrol post-treatment, resveratrol OGD-treatment, and resveratrol whole-processing group...
January 1, 2018: Cell Transplantation
Dan-Yang Liu, Tian-Yan Chi, Xue-Fei Ji, Peng Liu, Xiao-Xiao Qi, Lin Zhu, Zi-Qi Wang, Lin-Li, Ling Chen, Li-Bo Zou
Sigma-1 receptor (Sig-1R) activation has been shown to decrease infarct volume and enhance neuronal survival after brain ischemia-reperfusion (IR) in rodent models. The present study aims to investigate first the effect of Sig-1R activation on blood-brain barrier (BBB) disruption during experimental stroke. Male C57BL/6 mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 15 min, and the worst BBB leakage was observed on the 7th day after brain IR. To confirm the BBB protective role of Sig-1R, mice were divided into five groups (sham group, BCCAO group, PRE084 group, BD1047 group, PRE084 and BD1047 group; 29-35 mice for each group), and treated with agonist PRE084 (1 mg/kg) and/or antagonist BD1047 (1 mg/kg) for 7 days intraperitoneally once a day after BCCAO...
July 10, 2018: Experimental Neurology
Ji Man Hong, Mun Hee Choi, Sung-Il Sohn, Yang-Ha Hwang, Seong Hwan Ahn, Yeong-Bae Lee, Dong-Ick Shin, Ángel Chamorro, Dennis W Choi
BACKGROUND: The potential of neuroprotective agents should be revisited in the era of endovascular thrombectomy (EVT) for acute large-artery occlusion because their preclinical effects have been optimized for ischemia and reperfusion injury. Neu2000, a derivative of sulfasalazine, is a multi-target neuroprotectant. It selectively blocks N-methyl-D-aspartate receptors and scavenges for free radicals. This trial aimed to determine whether neuroprotectant administration before EVT is safe and leads to a more favorable outcome...
July 13, 2018: Trials
Maria Kovalska, Barbara Tothova, Libusa Kovalska, Zuzana Tatarkova, Dagmar Kalenska, Anna Tomascova, Marian Adamkov, Jan Lehotsky
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that results in massive hippocampal and neocortical neuronal loss leading to dementia and eventual death. The exact cause of Alzheimer's disease is not fully explored, although a number of risk factors have been recognized, including high plasma concentration of homocysteine (Hcy). Hyperhomocysteinemia (hHcy) is considered a strong, independent risk factor for stroke and dementia. However, the molecular background underlying these mechanisms linked with hHcy and ischemic stroke is not fully understood...
July 12, 2018: Neurochemical Research
Zengli Zhang, Pei Qin, Youliang Deng, Zhi Ma, Hang Guo, Haiyun Guo, Yushu Hou, Shiquan Wang, Wangyuan Zou, Yanyuan Sun, Yulong Ma, Wugang Hou
BACKGROUND: The steroid hormone estrogen (17-β-estradiol, E2) provides neuroprotection against cerebral ischemic injury by activating estrogen receptors. The novel estrogen receptor G protein-coupled receptor 30 (GPR30) is highly expressed in the brain and provides acute neuroprotection against stroke. However, the underlying mechanisms remain unclear. METHODS: In this study, ovariectomized female mice were subjected to middle cerebral artery occlusion (MCAO), and E2, G1, and ICI182780 were administered immediately upon reperfusion...
July 12, 2018: Journal of Neuroinflammation
Siu-Lung Chan, Nicole Bishop, Zhaojin Li, Marilyn J Cipolla
BACKGROUND AND PURPOSE: Aging and hypertension, comorbidities prevalent in the stroke population, are associated with poor collateral status and worsened stroke outcome. However, underlying mechanisms by which these conditions affect stroke outcome are not clear. We studied the role of PAI (plasminogen activator inhibitor)-1 that is increased in aging and hypertension on brain and vascular expression of inflammatory factors and perfusion that may contribute to worse stroke outcomes. METHODS: Aged (≈50 weeks) and young (≈18 weeks) spontaneously hypertensive rats (SHR) were subjected to ischemia by middle cerebral artery occlusion (2 hours) and reperfusion (2 hours) with or without treatment with the PAI-1 inhibitor TM5441...
July 10, 2018: Stroke; a Journal of Cerebral Circulation
Eva-Verena Griemert, Kirsten Recarte Pelz, Kristin Engelhard, Michael K Schäfer, Serge C Thal
After stroke, secondary brain damage is influenced by the extent of fibrin clot formation. This is counteracted by the endogenous fibrinolysis. Of major interest are the key players of the fibrinolytic plasminogen activator system including the urokinase plasminogen activator (uPA), the tissue-type plasminogen activator (tPA), and their endogenous inhibitors plasminogen activator inhibitor 1 (PAI-1) and PAI-2. The role of PAI-1 in brain injury is well established, whereas the importance of PAI-2 is unknown at present...
July 5, 2018: Translational Stroke Research
Di Ma, Liangshu Feng, Yingying Cheng, Meiying Xin, Jiulin You, Xiang Yin, Yulei Hao, Li Cui, Jiachun Feng
BACKGROUND: Stroke is the second leading cause of death worldwide and the most common cause of adult-acquired disability in many nations. Thus, attenuating the damage after ischemic injury and improving patient prognosis are of great importance. We have indicated that ischemic preconditioning (IP) can effectively reduce the damage of ischemia reperfusion and that inhibition of gap junctions may further reduce this damage. Although we confirmed that the function of gap junctions is closely associated with glutamate, we did not investigate the mechanism...
July 5, 2018: Journal of Neuroinflammation
Ruoxi Sun, Yichen Song, Shanshan Li, Zhanqiang Ma, Xueyang Deng, Qiang Fu, Rong Qu, Shiping Ma
Ischemic stroke is one of the most dangerous acute diseases which causes death or deformity. Apoptosis has been shown to play an important role in the development and pathogenesis of cerebral ischemia-reperfusion injury (I/R injury), but the related mechanism is unclear. Levo-tetrahydropalmatine (L-THP), a bioactive ingredient extracted from the Chinese herb Corydalis, can penetrate the blood-brain barrier and exert various pharmacological effects on neural tissues. The present study examined the neuroprotective effect of L-THP on neuronal apoptosis induced by cerebral I/R injury...
July 4, 2018: Journal of Molecular Neuroscience: MN
Robert J Henning, Marie Bourgeois, Raymond D Harbison
Poly(ADP-ribosyl)ation is an immediate cellular repair response to DNA damage and is catalyzed primarily by poly(ADP-ribose)polymerase-1 (PARP1), which is the most abundant of the 18 different PARP isoforms and accounts for more than 90% of the catalytic activity of PARP in the cell nucleus. Upon detection of a DNA strand break, PARP1 binds to the DNA, cleaves nicotinamide adenine dinucleotide between nicotinamide and ribose and then modifies the DNA nuclear acceptor proteins by formation of a bond between the protein and the ADP-ribose residue...
July 2, 2018: Cardiovascular Toxicology
Gilbert Aaron Lee, Teng-Nan Lin, Cheng-Yu Chen, Shin-Yi Mau, Wan-Zhen Huang, Yu-Chieh Kao, Ruo-Yu Ma, Nan-Shih Liao
Acute ischemic stroke is followed by a complex interplay between the brain and the immune system in which ischemia-reperfusion leads to a detrimental inflammatory response that causes brain injury. In the brain, IL-15 is expressed by astrocytes, neurons and microglia. Previous study showed that ischemia-reperfusion induces expression of IL-15 by astrocytes. Transgenic over-expression of IL-15 in astrocytes aggravates ischemia-reperfusion brain damage by increasing the levels and promoting the effector functions of CD8+ T and NK cells...
June 26, 2018: Brain, Behavior, and Immunity
Xinwei Wu, Xuemei Li, Yi Liu, Nannan Yuan, Chengwen Li, Zhimin Kang, Xinlei Zhang, Yuning Xia, Yimeng Hao, Yongxing Tan
Cerebral ischemia/reperfusion injury (IRI) is a serious complication during the treatment of stroke patients with very few effective clinical treatment. Hydrogen (H2) can protect mitochondria function and have favorable therapeutic effects on cerebral IRI. Mitophagy plays an important role in eliminating damaged or dysfunctional mitochondria and maintaining mitochondria homeostasis. However, whether the protection of H2 on cerebral IRI is via regulating mitophagy is still unknown. In this study, OGD/R damaged hippocampal neurons were used to mimic cerebral IRI in vivo and we detected the effect of H2, Rap(autophagy activator) and 3-MA(autophagy inhibitor) on OGD/R neurons...
June 26, 2018: Brain Research
Yun-Liang Xie, Bo Zhang, Ling Jing
OBJECTIVE:  To explore the potential effect of miR-125b on p53-mediated regulation of Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rats with cerebral ischemia-reperfusion (CIR) injury. METHODS:  Sprague-Dawley (SD) rats were used to conduct CIR injury and injected with miR-125b mimic/inhibitor or p53 inhibitor (Pifithrin-α, PFT-α). Dual-luciferase reporter gene assay was used to analyze the targeting relationship between miR-125b and p53. Longa scoring and Triphenyl tetrazolinm chloride (TTC) staining were used to test the neurologic function and determine infarct size, respectively...
June 29, 2018: Neurological Research
Nathanael Matei, Justin Camara, Devin McBride, Richard Camara, Ningbo Xu, Jiping Tang, John H Zhang
After ischemic stroke, apoptosis of neurons is a primary factor in determining outcome. Wnt3a is a naturally occurring protein that has been shown to have protective effects in the brain for traumatic brain injury. Although wnt3a has been investigated in the phenomena of neurogenesis, anti-apoptosis, and anti-inflammation, it has never been investigated as a therapy for stroke. We hypothesized that the potential neuroprotective agent wnt3a would reduce infarction and improve behavior following ischemic stroke by attenuating neuronal apoptosis and promoting cell survival through the Frizzled-1/PIWI1a/FOXM1 pathway in MCAO rats...
June 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
T F Pedersen, J Budtz-Lilly, C N Petersen, J Hyldgaard, J-O Schmidt, R Kroijer, M-L Grønholdt, N Eldrup
Background: Remote ischaemic preconditioning (RIPC) has been suggested as a means of protecting vital organs from reperfusion injury during major vascular surgery. This study was designed to determine whether RIPC could reduce the incidence of perioperative myocardial infarction (MI) during open surgery for ruptured abdominal aortic aneurysm (AAA). Secondary aims were to see if RIPC could reduce 30-day mortality, multiple organ failure, acute intestinal ischaemia, acute kidney injury and ischaemic stroke...
June 2018: BJS open
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