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X F Guo, Y N Zhao, J M Li, C X Chen, S X Li
Objective: To compare the changes in the expression of mTOR and beclin1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion, so as to explore the roles of mTOR/autophagy pathway in global cerebral ischemia/reperfusion injure aggravated by intermittent hypoxia. Methods: One hundred healthy male Wistar rats were randomly divided into: sham operation group(SO group, n=20), intermittent hypoxia group(IH group, n=20), merely ischemia/reperfusion group(I/R group, n=20), intermittent hypoxia ischemia/reperfusion group(IH+ I/R group, n=20), intermittent hypoxia ischemia/reperfusion+ mTOR inhibitor group(Inhibitor group, n=20)...
October 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Hamid Abbasi, Laura Bennet, Alistair J Gunn, Charles P Unsworth
Currently, there are no developed methods to detect sharp wave transients that exist in the latent phase after hypoxia-ischemia (HI) in the electroencephalogram (EEG) in order to determine if these micro-scale transients are potential biomarkers of HI. A major issue with sharp waves in the HI-EEG is that they possess a large variability in their sharp wave profile making it difficult to build a compact 'footprint of uncertainty' (FOU) required for ideal performance of a Type-2 fuzzy logic system (FLS) classifier...
August 18, 2016: International Journal of Neural Systems
Håvard Tetlie Garberg, Marianne U Huun, Lars O Baumbusch, Monica Åsegg-Atneosen, Rønnaug Solberg, Ola Didrik Saugstad
BACKGROUND: There is a lack of reliable biomarkers that can identify and grade acute hypoxic-ischemic encephalopathy in newborns. MicroRNAs (miRNA) are short, non-coding strands of RNA that are released into the circulation in response to tissue stress and injury. Some miRNAs are highly tissue specific and thus may potentially be non-invasive biomarkers of neonatal hypoxic-ischemic brain injury. OBJECTIVE: The aim of this study was to characterize the temporal expression of selected circulating miRNAs in a clinically relevant piglet model of neonatal hypoxia-ischemia (HI)...
October 18, 2016: Neonatology
Quratulane Gillani, Muhammad Ali, Furhan Iqbal
Interleukin (IL) 6 and 18 plays an important role in inflammatory response following hypoxia ischemia encephalopathy (HIE). Present study was designed to demonstrate the effect of two GABAB receptor antagonists (CGP 35348 and 55845), respectively, on the serum IL6 and IL 18 concentrations in albino mice. Albino mice pups (of both genders) were subjected to Murine model of hypoxia-ischemia encephalopathy on postnatal day 10 (right common carotid artery was ligated followed by 8% hypoxia for 25 minutes). After neonatal brain damage and following weaning, mice were divided in three groups, in gender specific manner, and fed on normal rodent diet till they were 13 week old...
September 2016: Pakistan Journal of Pharmaceutical Sciences
Sujuan Liu, Juan Mao, Tinghua Wang, Xuemei Fu
Aquaporin-4 (AQP4), a water-channel protein, controls water fluxes into and out of the brain parenchyma. The role of AQP4 in brain edema formation and resolution remains controversial. This study therefore determined the roles of AQP4 in brain edema and explored the underlying molecular mechanism. We established hypoxia-ischemia (HI) neonatal rat model in vivo and HI cell model in vitro, which were administrated with lentiviral or shRNA vector, respectively. We found that the neurologic deficit and motor dysfunction could be induced by HI with more serious brain damage after longer HI time, and swollen cells with enlarged surrounding space were observed after HI induction...
October 10, 2016: Molecular Neurobiology
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
Daniel Gruneberg, Felipe A Montellano, Konstanze Plaschke, Lexiao Li, Hugo H Marti, Reiner Kunze
Episodes of cerebral hypoxia/ischemia increase the risk of dementia, which is associated with impaired learning and memory. Previous studies in rodent models of dementia indicated a favorable effect of the hypoxia-inducible factor (HIF) targets VEGF (vascular endothelial growth factor) and erythropoietin (Epo). In the present study we thus investigated whether activation of the entire adaptive HIF pathway in neurons by cell-specific deletion of the HIF suppressor prolyl-4-hydroxylase 2 (PHD2) improves cognitive abilities in young (3months) and old (18-28months) mice suffering from chronic brain hypoperfusion...
October 5, 2016: Experimental Neurology
Penha Cristina Barradas, Tiago Savignon, Alex C Manhães, Frank Tenório, Alan P da Costa, Marta C Cunha-Rodrigues, Juliana Vaillant
Hypoxic-ischemic (HI) injury is an important cause of death and disabilities. Despite all improvements in neonatal care, the number of children who suffer some kind of injury during birth has remained stable in the last decade. A great number of studies have shown alterations in neural cells and many animal models have been proposed in the last 5 decades. Robinson et al. (2005) proposed an HI model in which the uterine arteries are temporarily clamped on the 18th gestation day. The findings were quite similar to the ones observed in postmortem studies...
2016: Advances in Experimental Medicine and Biology
Ursula I Tuor, Manasi Sule, Min Qiao
PURPOSE: To determine whether damage to neonatal brain is exacerbated with multiple mild cerebral insults as detected with MRI and corroborated using histology. MATERIALS AND METHODS: The combined brain injury produced by multiple procedures was compared in neonatal rats having: Sham surgery at P5, Sham surgery at P5 plus a diffuse mild transient unilateral cerebral hypoxia ischemia (HI) at P7, HI alone, and a minor photothrombotic (PT) stroke at P5 followed by HI...
October 1, 2016: Neuroscience Letters
Ryan J Felling, Matthew V Covey, Paul Wolujewicz, Mona Batish, Steven W Levison
Brain injuries, such as cerebral hypoxia-ischemia (H-I), induce a regenerative response from the neural stem/progenitors (NSPs) of the subventricular zone (SVZ); however, the mechanisms that regulate this expansion have not yet been fully elucidated. The Notch- Delta-Serrate-Lag2 (DSL) signaling pathway is considered essential for the maintenance of neural stem cells, but it is not known if it is necessary for the expansion of the NSPs subsequent to perinatal H-I injury. Therefore, the aim of this study was to investigate whether this pathway contributes to NSP expansion in the SVZ after H-I and, if so, to establish whether this pathway is directly induced by H-I or regulated by paracrine factors...
December 2016: Journal of Neuroscience Research
Fangfang Yan, Chao Jiang, Yan Meng, Huijuan Li, Lie Yu, Xiaojie Fu, Youcai Tang, Meimei Zhang
Erythropoietin (EPO) is important for angiogenesis after hypoxia/ischemia. In this study, we investigated whether recombinant human erythropoietin (rhEPO) can enhance angiogenesis, and promote cognitive function through vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway in a rat model of hypoxic-ischemic encephalopathy (HIE). RhEPO, selective VEGFR2 inhibitor (SU5416) or vehicle was administrated by intraperitoneal injection. The assessment for cognitive function begins on day 60 after anoxia...
September 19, 2016: Brain Research
Constantino Tomas-Sanchez, Victor Manuel Blanco-Alvarez, Juan Antonio Gonzalez-Barrios, Daniel Martinez-Fong, Guadalupe Garcia-Robles, Guadalupe Soto-Rodriguez, Eduardo Brambila, Maricela Torres-Soto, Alejandro Gonzalez-Vazquez, Ana Karina Aguilar-Peralta, José-Luis Garate-Morales, Luis-Angel Aguilar-Carrasco, Daniel I Limón, Jorge Cebada, Bertha Alicia Leon-Chavez
Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points...
2016: Journal of Immunology Research
Luca Braccioli, Cobi J Heijnen, Paul J Coffer, Cora H Nijboer
BACKGROUND: Hypoxic-ischemic (HI) encephalopathy causes mortality and severe morbidity in neonates. Treatments with a therapeutic window >6 h are currently not available. Here, we explored whether delayed transplantation of allogenic neural stem cells (NSCs) at 10 d after HI could be a tool to repair HI brain injury and improve behavioral impairments. METHODS: HI was induced in 9-d-old mice. Animals received NSCs or vehicle intracranially in the hippocampus at 10 d post-HI...
October 5, 2016: Pediatric Research
Binzhi Tang, Dejian Wang, Maojun Li, Qing Wu, Qian Yang, Wei Shi, Changhui Chen
BACKGROUND: Hypoxia/ischemia (HI) brain injury is a common central nervous system insult in newborns. Studies have demonstrated bioactivity of ginsenoside Rg1 in increasing neural viability and promoting angiogenesis. However, there are few reports on roles of Rg1 in brain repair of neonatal HI, and the mechanisms involved are unclear. METHODS: a neonatal HI model was established by a modified Rice-Vannucci model (RVM) and pups received ginsenoside Rg1 or monosialotetrahexosyl ganglioside (GM1) treatment...
October 5, 2016: Pediatric Research
Jennifer K Lee, Bing Wang, Michael Reyes, Jillian S Armstrong, Ewa Kulikowicz, Polan T Santos, Jeong-Hoo Lee, Raymond C Koehler, Lee J Martin
Therapeutic hypothermia provides incomplete neuroprotection after hypoxia-ischemia (HI)-induced brain injury in neonates. We previously showed that cortical neuron and white matter apoptosis are promoted by hypothermia and early rewarming in a piglet model of HI. The unfolded protein response (UPR) may be one of the potential mediators of this cell death. Here, neonatal piglets underwent HI or sham surgery followed by 29 h of normothermia, 2 h of normothermia + 27 h of hypothermia or 18 h of hypothermia + rewarming...
September 14, 2016: Developmental Neuroscience
S Wolf, N Hainz, A Beckmann, C Maack, M D Menger, T Tschernig, C Meier
Perinatal hypoxia is a critical complication during delivery and is mostly studied in animal models of postnatal hypoxic-ischemic brain injury. We here studied the effects of postnatal hypoxic-ischemic brain injury in two different sub-strains of C57BL/6 mice, i.e. C57BL/6J and C57BL/6N mice. These two sub-strains show different metabolic properties, for instance an impaired glucose tolerance in C57BL/6J mice. Genetically, this was linked to differences in their nicotinamide nucleotide transhydrogenase (Nnt) genes: In C57BL/6J mice, exons 7-11 of the Nnt gene are deleted, resulting in the absence of functional Nnt protein...
November 1, 2016: Brain Research
Mathilde Chevin, Clémence Guiraut, Caroline Maurice-Gelinas, Jessica Deslauriers, Sylvain Grignon, Guillaume Sébire
BACKGROUND: Despite the recent introduction of hypothermia as a mandatory standard of care, the incidence of neonatal encephalopathy in full-term newborns and its devastating neuro-behavioral outcomes continues to be a major individual, familial and social issue. Neonatal encephalopathy is mainly due to the compounding and interacting effects of hypoxia-ischemia and inflammation resulting from placental and other perinatal infections. It is unclear why hypothermia is effective in alleviating neonatal encephalopathy in some, but not all, full-term newborns...
September 9, 2016: International Journal of Developmental Neuroscience
Armin Yazdani, Zehra Khoja, Aaron Johnstone, Laura Dale, Emmanouil Rampakakis, Pia Wintermark
Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control...
September 10, 2016: Developmental Neuroscience
Hiroko Mori, Ken Momosaki, Jun Kido, Tetsuo Naramura, Kenichi Tanaka, Shirou Matsumoto, Kimitoshi Nakamura, Hiroshi Mitsubuchi, Fumio Endo, Masanori Iwai
BACKGROUND: Glycine protected adult brains against injury in an experimental model of stroke. However, because the ischemic response of neonatal brains differs from that of adult brains, we examined the neuroprotective efficacy of glycine and associated mechanisms in an experimental model of neonatal hypoxic-ischemic (HI) encephalopathy. METHODS: Neonatal (P7) Wister rats were randomly divided into an untreated group (non-HI) and two HI groups that were treated with left common carotid artery ligation and saline control or glycine...
September 10, 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
Peng Liu, Rui Yang, Zelan Zuo
BACKGROUND: A new rectal cooling device for therapeutic hypothermia (TH) therapy is designed and is applied in TH treatment of SD rats with ischemic-hypoxic brain damage. METHODS: Healthy adult SD rats (n = 45) were randomly assigned into four groups: the healthy control group (n = 5), the ischemia and hypoxia group (n = 10), the rectal TH cooling group (n = 18), and the ice blanket TH cooling group (n = 11). The rats in the rectal cooling and ice blanket TH groups received 12 h treatment after hypoxic-ischemic brain damage had been established, while those in the ischemia and hypoxia group did not...
2016: BMC Anesthesiology
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