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https://www.readbyqxmd.com/read/28925896/allopurinol-old-drug-new-indication-in-neonates
#1
Kim V Annink, Axel R Franz, Jan B Derks, Mario Rüdiger, Frank van Bel, Manon J N L Benders
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is an important cause of neonatal mortality and neurological morbidity, even despite hypothermia treatment. Neuronal damage in these infants is partly caused by the production of superoxides via the xanthine-oxidase pathway and concomitant free radical formation. Allopurinol is a xanthine-oxidase inhibitor and can potentially reduce the formation of these superoxides that lead to brain damage in HIE. METHODS: The aim of this review is to provide an overview of the animal and clinical data about the neuroprotective effect of allopurinol in HIE and the relevant mechanisms leading to brain injury in HIE...
September 18, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28925083/selective-knockout-of-astrocytic-na-h-exchanger-isoform-1-reduces-astrogliosis-bbb-damage-infarction-and-improves-neurological-function-after-ischemic-stroke
#2
Gulnaz Begum, Shanshan Song, Shaoxia Wang, Hanshu Zhao, Mohammad Iqbal H Bhuiyan, Eric Li, Rachel Nepomuceno, Qing Ye, Ming Sun, Michael Joseph Calderon, Donna B Stolz, Claudette St Croix, Simon C Watkins, Yinhuai Chen, Pingnian He, Gary E Shull, Dandan Sun
Stimulation of Na(+) /H(+) exchanger isoform 1 (NHE1) in astrocytes causes ionic dysregulation under ischemic conditions. In this study, we created a Nhe1(flox/flox) (Nhe1(f/f) ) mouse line with exon 5 of Nhe1 flanked with two loxP sites and selective ablation of Nhe1 in astrocytes was achieved by crossing Nhe1(f/f) mice with Gfap-Cre(ERT2) Cre-recombinase mice. Gfap-Cre(ERT2+/-) ;Nhe1(f/f) mice at postnatal day 60-90 were treated with either corn oil or tamoxifen (Tam, 75 mg/kg/day, i.p.) for 5 days. After 30 days post-injection, mice underwent transient middle cerebral artery occlusion (tMCAO) to induce ischemic stroke...
September 19, 2017: Glia
https://www.readbyqxmd.com/read/28924549/potassium-2-1-hydroxypentyl-benzoate-attenuates-neuronal-apoptosis-in-neuron-astrocyte-co-culture-system-through-neurotrophy-and-neuroinflammation-pathway
#3
Dongmei Liu, Man Zhang, Xianfang Rong, Jiang Li, Xiaoliang Wang
Potassium 2-(1-hydroxypentyl)-benzoate (d,l-PHPB), a new drug candidate for ischemic stroke at the phase II clinic trial, has been shown to protect neurons by inhibiting oxidative injury and reducing neuron apoptosis in previous studies. But the mechanisms of d,l-PHPB remain to be studied. In this study, a neuron-astrocytes co-culture system was used to elucidate the roles of astrocytes in neuroprotection of d,l-PHPB under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. Our data showed that d,l-PHPB reduced neuronal apoptosis in mono-culture system and this effect was enhanced in neuron-astrocyte co-culture system under the OGD/R condition...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28924010/microrna-1906-a-novel-regulator-of-toll-like-receptor-4-ameliorates-ischemic-injury-after-experimental-stroke-in-mice
#4
Xiaomeng Xu, Zhuoyu Wen, Nan Zhao, Xiaohui Xu, Fang Wang, Jie Gao, Yongjun Jiang, Xinfeng Liu
Toll-like receptor 4 (TLR4) is a pro-inflammatory cascade initiator in post-stroke inflammation. In this study, miR-1906, a novel regulator of TLR4, was identified via in silico analysis and microRNA profiling in male adult mice, and its expression was then quantitated in the ischemic hemisphere. We found miR-1906 to be significantly brain-enriched in the ischemic hemisphere and even more drastically enriched in the peri-infarct regions. Furthermore, in vitro experiments demonstrated that during oxygen-glucose deprivation (OGD), miR-1906 expression was increased in glial cells but decreased in neurons...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923791/gja1-20k-arranges-actin-to-guide-cx43-delivery-to-cardiac-intercalated-discs
#5
Wassim A Basheer, Shaohua Xiao, Irina Epifantseva, Ying Fu, Andre G Kleber, TingTing Hong, Robin M Shaw
Rationale: Delivery of connexin 43 (Cx43) to the intercalated disc is a continuous and rapid process critical for intercellular coupling. By a pathway of targeted delivery involving microtubule highways, vesicles of Cx43 hemichannels are efficiently trafficked to adherens junctions at intercalated discs. It has also been identified that actin provides rest stops for Cx43 forward trafficking, and that Cx43 has a 20kDa internally translated small C-terminus isoform (GJA1-20k) which is required for full-length Cx43 trafficking, but by an unknown mechanism...
September 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28923648/octreotide-ameliorates-renal-ischemia-reperfusion-injury-via-antioxidation-and-anti-inflammation
#6
Z Xu, K Zhao, P Han, X Qi, W Zhang, T Niu
Oxidative stress, calcium overload, inflammation, cellular necrosis, and apoptosis are implicated in renal ischemic/reperfusion injury (RIRI). Because octreotide (OCT) is protective in retinal IRI, the effect of OCT on mouse RIRI and the mechanisms involved were investigated. The RIRI model was induced in male C57BL/6 mice, and the mice were then treated with saline or OCT. Serum and kidneys were subjected to periodic acid-Schiff staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28922144/short-term-hypoxia-and-vasa-recta-function-in-kidney-slices
#7
D Braun, S Dietze, T M J Pahlitzsch, I C Wennysia, P B Persson, M Ludwig, A Patzak
BACKGROUND: Vasa recta (VR) supply the inner part of outer renal medulla an area at risk for hypoxic damages. OBJECTIVE: We hypothesize increased vasoreactivity after hypoxia/re-oxygenation (H/R) in VR, which might contribute to the reduced medullary perfusion after an ischemic event. METHODS: Live kidney slices (200μm) from SD rats were used for functional experiments. TUNEL assay and H&E staining were used to estimate slice viability. Kidney slices were treated with carbogen or hypoxia (1% O2) for 60 or 90 min and vasoreactivity to Ang II (10-7 M) was recorded by DIC microscopy after re-oxygenation with carbogen...
September 11, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28920945/neutrophils-a-cornerstone-of-liver-ischemia-and-reperfusion-injury
#8
Thiago Henrique Caldeira de Oliveira, Pedro Elias Marques, Paul Proost, Mauro Martins M Teixeira
Ischemia-reperfusion injury (IRI) is the main cause of morbidity and mortality due to graft rejection after liver transplantation. During IRI, an intense inflammatory process occurs in the liver. This hepatic inflammation is initiated by the ischemic period but occurs mainly during the reperfusion phase, and is characterized by a large neutrophil recruitment to the liver. Production of cytokines, chemokines, and danger signals results in activation of resident hepatocytes, leukocytes, and Kupffer cells. The role of neutrophils as the main amplifiers of liver injury in IRI has been recognized in many publications...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28920462/involvement-of-atrial-natriuretic-peptide-in-abrogated-cardioprotective-effect-of-ischemic-preconditioning-in-ovariectomized-rat-heart
#9
V K Vishwakarma, A Goyal, J K Gupta, P K Upadhyay, H N Yadav
BACKGROUND: Nitric oxide (NO) is an effective mediator of ischemic preconditioning (IPC)-induced cardioprotection. Atrial natriuretic peptide (ANP) is downregulated after ovariectomy, which results in reduction in the level of NO. The present study deals with the investigation of the role of ANP in abrogated cardioprotective effect of IPC in the ovariectomized rat heart. METHODS: Heart was isolated from ovariectomized rat and mounted on Langendorff's apparatus, subjected to 30 min of ischemia and 120 min of reperfusion...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28920042/mitochondrial-atp-sensitive-potassium-channels-play-a-role-in-reducing-both-myocardial-infarction-and-reperfusion-arrhythmia-in-remote-ischemic-preconditioned-hearts
#10
Young-Ho Jang, June-Hong Kim, Yong-Cheol Lee
BACKGROUND: Mitochondrial ATP-sensitive potassium (mKATP) channels play a role in reperfusion arrhythmias (RAs) in ischemia-reperfusion (I/R) injury. Evidence suggests that remote ischemic preconditioning (RIPC) reduces RAs, however not much is known on the mechanistic role of mKATP in RIPC. We evaluated whether mKATP channels are associated with reducing arrhythmia and infarct size in RIPC. METHODS: Isolated rat hearts received 30 minutes of regional ischemia followed by 2 hours of reperfusion through the Langendorff perfusion system...
February 2017: Anesthesiology and Pain Medicine
https://www.readbyqxmd.com/read/28918255/microglia-mediated-baff-baffr-ligation-promotes-neuronal-survival-in-brain-ischemia-injury
#11
Kai Li, Wei Yu, Rangjuan Cao, Zhihua Zhu, Guoqing Zhao
The innate immune responses of brain to vascular occlusion are primarily orchestrated by activated microglia. However, the roles of microglia in inflammatory responses to brain ischemic injuries are controversial. Here, we report a new mechanism by which microglia confer protective effects on ischemic neuronal cells. We found that under ischemic condition, the B-cell activating factor (BAFF) was vastly upregulated in microglia and this upregulation could at least be attributed to JAK-STAT signaling pathway activated by IFN-γ and IL-10, which were spatio-temporally enriched in I/R injured brain as well...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28917976/low-molecular-weight-fucoidan-ameliorates-hindlimb-ischemic-injury-in-type-2-diabetic-rats
#12
Zhiqiang Wang, Tiantian Liu, Xiaoping Chen, Hongjie You, Quanbin Zhang, Jingyi Xue, Yuanyuan Zheng, Dali Luo
ETHNOPHARMACOLOGICAL RELEVANCE: Low molecular weight fucoidan (LMWF), extracted from Laminaria japonica Areschoug, is a traditional Chinese medicine, commonly used to alleviate edema, particularly for feet with numbness and pain. AIM OF THE STUDY: Diabetic mellitus (DM) patients are at high risk of developing peripheral arterial disease (PAD). Individuals with DM and PAD co-morbidity have a much higher risk of critical limb ischemia. LMWF showed several beneficial effects, such as anti-inflammation, anti-thrombosis, and enhancing revascularization...
September 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28916603/phase-2a-clinical-trial-of-mitochondrial-protection-elamipretide-during-stent-revascularization-in-patients-with-atherosclerotic-renal-artery-stenosis
#13
Ahmed Saad, Sandra M S Herrmann, Alfonso Eirin, Christopher M Ferguson, James F Glockner, Haraldur Bjarnason, Michael A McKusick, Sanjay Misra, Lilach O Lerman, Stephen C Textor
BACKGROUND: Atherosclerotic renal artery stenosis reduces renal blood flow (RBF) and amplifies stenotic kidney hypoxia. Revascularization with percutaneous transluminal renal angioplasty (PTRA) and stenting often fails to recover renal function, possibly because of ischemia/reperfusion injury developing after PTRA. Elamipretide is a mitochondrial-targeted peptide that binds to cardiolipin and stabilizes mitochondrial function. We tested the hypothesis that elamipretide plus PTRA would improve renal function, oxygenation, and RBF in patients with atherosclerotic renal artery stenosis undergoing PTRA...
September 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28916471/the-pyk2-mcu-pathway-in-the-rat-middle-cerebral-artery-occlusion-model-of-ischemic-stroke
#14
Kun Zhang, Jiajia Yan, Liang Wang, Xinying Tian, Tong Zhang, Li Guo, Bin Li, Wang Wang, Xiaoyun Liu
Mitochondrial dysfunction caused by Ca(2+) overload plays an important role in ischemia-induced brain damage. Mitochondrial calcium uniporter (MCU), located on the mitochondrial inner membrane, is the major channel responsible for mitochondrial Ca(2+) uptake. Activated proline-rich tyrosine kinase 2 (Pyk2) can directly phosphorylate MCU, which enhances mitochondrial Ca(2+) uptake in cardiomyocytes. It has been suggested that the Pyk2/MCU pathway may be a novel therapeutic target in stress-induced cellular apoptosis...
September 12, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28915969/hyperglycemia-in-acute-ischemic-stroke-is-it-time-to-re-evaluate-our-understanding
#15
Rwoof Reshi, Chris Streib, Mustapha Ezzeddine, Michelle Biros, Benjamin Miller, Kamakshi Lakshminarayan, David Anderson, Agnieszka Ardelt
Among 700,000 new and recurrent ischemic stroke patients per year, forty percent are hyperglycemic on admission. In-vitro, hyperglycemia is toxic to neurons. Acute ischemic stroke patients who are hyperglycemic on admission experience higher morbidity and mortality. Results of multiple trials have provided no evidence supporting benefit in achieving normoglycemia. On the contrary, there is some evidence that tight glycemic control in acute brain injury is associated with poor outcome. Current consensus derived guidelines from the American Heart Association/American Stroke Association recommend an upper limit of blood glucose of 140-180mg/dl, as there is no evidence to support strict control...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28915329/mitophagy-as-a-protective-mechanism-against-myocardial-stress
#16
Jihoon Nah, Shigeki Miyamoto, Junichi Sadoshima
Mitochondria are dynamic organelles that can undergo fusion, fission, biogenesis, and autophagic elimination to maintain mitochondrial quality control. Since the heart is in constant need of high amounts of energy, mitochondria, as a central energy supply source, play a crucial role in maintaining optimal cardiac performance. Therefore, it is reasonable to assume that mitochondrial dysfunction is associated with the pathophysiology of heart diseases. In non-dividing, post-mitotic cells such as cardiomyocytes, elimination of dysfunctional organelles is essential to maintaining cellular function because non-dividing cells cannot dilute dysfunctional organelles through cell division...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28914418/spermidine-rescues-proximal-tubular-cells-from-oxidative-stress-and-necrosis-after-ischemic-acute-kidney-injury
#17
Jinu Kim
Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality rate, which is attributed to tubular oxidative stress and necrosis; however, an effective approach to limit IRI remains elusive. Spermidine, a naturally occurring polyamine, protects yeast cells against aging through the inhibition of oxidative stress and necrosis. In the present study, spermidine supplementation markedly attenuated increases in plasma creatinine concentration and tubular injury score after IRI. In addition, exogenous spermidine potently inhibited oxidative stress, especially lipid peroxidation after IRI in kidneys and exposure to hydrogen peroxide in kidney proximal tubular cells, suppressing plasma membrane disruption and necrosis...
September 15, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28914132/reverse-electron-transfer-results-in-a-loss-of-flavin-from-mitochondrial-complex-i-potential-mechanism-for-brain-ischemia-reperfusion-injury
#18
Anna Stepanova, Anja Kahl, Csaba Konrad, Vadim Ten, Anatoly S Starkov, Alexander Galkin
Ischemic stroke is one of the most prevalent sources of disability in the world. The major brain tissue damage takes place upon the reperfusion of ischemic tissue. Energy failure due to alterations in mitochondrial metabolism and elevated production of reactive oxygen species (ROS) is one of the main causes of brain ischemia-reperfusion (IR) damage. Ischemia resulted in the accumulation of succinate in tissues, which favors the process of reverse electron transfer (RET) when a fraction of electrons derived from succinate is directed to mitochondrial complex I for the reduction of matrix NAD(+)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28914129/maternal-high-fat-diet-programs-cerebrovascular-remodeling-in-adult-rat-offspring
#19
ChengCheng Lin, XiaoYun Wu, YuLei Zhou, Bei Shao, XiaoTing Niu, WanLi Zhang, YuanShao Lin
Maternal environmental factors such as diet have consequences on later health of the offspring. We found that maternal high-fat diet (HFD) exposure renders adult offspring brain more susceptible to ischemic injury. The present study was further to investigate whether HFD consumption during rat pregnancy and lactation influences the cerebral vasculature in adult male offspring. Besides the endothelial damage observed in the transmission electron microscopy, the MCAs of offspring from fat-fed dams fed with control diet (HFD/C) also displayed increased wall thickness and media/lumen ratio, suggesting that cerebrovascular hypertrophy or hyperplasia occurs...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28913846/cardioprotective-effects-of-pomegranate-punica-granatum-juice-in-patients-with-ischemic-heart-disease
#20
Zahra Razani, Mostafa Dastani, Hamid Reza Kazerani
Ischemic heart disease is the leading cause of mortality worldwide. The purpose of this study was to evaluate the cardioprotective effects of pomegranate juice in patients with ischemic heart disease. One hundred patients, diagnosed with unstable angina or myocardial infarction, were randomly assigned to the test and the control groups (n = 50, each). During 5 days of hospitalization, in addition to the conventional medical therapies, the test groups received 220 mL pomegranate juice, daily. During the hospitalization period, the blood pressure, heart rate, as well as the intensity, occurrence, and duration of the angina were evaluated on a regular basis...
September 15, 2017: Phytotherapy Research: PTR
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