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Cerebral hypoxia

Ekaterina Turlova, Zhong-Ping Feng, Hong-Shuo Sun
Stroke is one of the major causes of mortality and morbidity worldwide, yet novel therapeutic treatments for this condition are lacking. This review focuses on the roles of the transient receptor potential melastatin 2 (TRPM2) ion channels in cellular damage following hypoxia-ischemia and their potential as a future therapeutic target for stroke. Here, we highlight the complex molecular signaling that takes place in neurons, glial cells and the blood-brain barrier following ischemic insult. We also describe the evidence of TRPM2 involvement in these processes, as shown from numerous in vitro and in vivo studies that utilize genetic and pharmacological approaches...
March 15, 2018: Acta Pharmacologica Sinica
Vasilije Stambolija, Martina Miklić Bublić, Marin Lozić, Jakob Nemir, Miroslav Ščap
Background: Low brain tissue oxygen tension (PbtO2 ), or brain hypoxia, is an independent predictor of poor outcome. Increasing inspirational fraction of oxygen could have a significant influence on treating lower PbtO2 . Combined PbtO2 therapy, compared to the approach that focus only on regulation of cerebral perfusion pressure and intracranial pressure, shows better patient outcomes. Monitoring of PbtO2 could be helpful in individualizing treatment, preventing or limiting secondary brain injury, and maintaining better patient outcome...
2018: Surgical Neurology International
Xin-Rui Han, Xin Wen, Yong-Jian Wang, Shan Wang, Min Shen, Zi-Feng Zhang, Shao-Hua Fan, Qun Shan, Liang Wang, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
Hypoxia-ischaemia (HI) remains a major cause of foetal brain damage presented a scarcity of effective therapeutic approaches. Dexmedetomidine (DEX) and microRNA-140-5p (miR-140-5p) have been highlighted due to its potentially significant role in the treatment of cerebral ischaemia. This study was to investigate the role by which miR-140-5p provides cerebral protection using DEX to treat hypoxic-ischaemic brain damage (HIBD) in neonatal rats via the Wnt/β-catenin signalling pathway. The HIBD rat models were established and allocated into various groups with different treatment plans, and eight SD rats into sham group...
March 13, 2018: Journal of Cellular and Molecular Medicine
Ruiqing Ni, Markus Vaas, Wuwei Ren, Jan Klohs
Oxygen metabolism and matrix metalloproteinases (MMPs) play important roles in the pathophysiology of cerebral ischemia. Using multispectral optoacoustic tomography (MSOT) imaging, we visualized in vivo changes in cerebral tissue oxygenation during 1 h of transient middle cerebral artery occlusion (tMCAO) and at 48 h after reperfusion together with MMP activity using an MMP-activatable probe. The deoxyhemoglobin, oxyhemoglobin, and MMP signals were coregistered with structural magnetic resonance imaging data...
January 2018: Neurophotonics
Xinhua Zhan, Boryana Stamova, Frank R Sharp
This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer's disease (AD). This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex...
2018: Frontiers in Aging Neuroscience
Shih-Huang Tai, Wei-Ting Lee, Ai-Chiang Lee, Yu-Wen Lin, Hsin-Yi Hung, Sheng-Yang Huang, Tian-Shung Wu, E-Jian Lee
3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), has been demonstrated to inhibit platelet aggregation, vascular contraction and hypoxia‑inducible factor 1 activity in vitro and in vivo. The present study investigated the neuroprotective efficacy of YC‑1 in cultured neurons exposed to glutamate‑induced excitotoxicity and in an animal model of stroke. In a cortical neuronal culture model, YC‑1 demonstrated neurotoxicity at a concentration >100 µM, and YC‑1 (10‑30 µM) achieved potent cytoprotection against glutamate‑induced neuronal damage...
March 1, 2018: Molecular Medicine Reports
Shashikant L Sholapurkar
The survival of cardiotocography (CTG) as a tool for intrapartum fetal monitoring seems threatened somewhat unjustifiably and unwittingly despite the absence of better alternatives. Fetal heart rate (FHR) decelerations are center-stage (most important) in the interpretation of CTG with maximum impact on three-tier classification. The pattern-discrimination of FHR decelerations is inexorably linked to their nomenclature. Unscientific or flawed nomenclature of decelerations can explain the dysfunctional CTG interpretation leading to errors in detection of acidemic fetuses...
April 2018: Journal of Clinical Medicine Research
Tao Xiong, Yi Qu, Huiqin Wang, Hongju Chen, Jianghu Zhu, Fengyan Zhao, Rong Zou, Li Zhang, Dezhi Mu
Glycogen synthase kinase 3 beta (GSK-3β) plays an important role in neurological outcomes after brain injury. However, its roles and mechanisms in hypoxia-ischemia (HI) are unclear. Activation of mTOR complex 1 (mTORC1) has been proven to induce the synthesis of proteins associated with regeneration. We hypothesized that GSK-3β inhibition could activate the mTORC1 signaling pathway, which may reduce axonal injury and induce synaptic protein synthesis and functional recovery of synapses after HI. By analyzing a P7 rat model of cerebral HI and an in vitro ischemic (oxygen glucose deprivation) model, we found that GSK-3β inhibitors (GSK-3β siRNA or lithium chloride) activated mTORC1 signaling, leading to increased expression of synaptic proteins, including synapsin 1, PSD95, and GluR1, and the microtubule-associated protein Tau and decreased expression of the axonal injury-associated protein amyloid precursor protein...
February 28, 2018: Journal of Neuropathology and Experimental Neurology
Michael Furian, Sara E Hartmann, Tsogyal D Latshang, Deborah Flueck, Christian Murer, Philipp M Scheiwiller, Batyr Osmonov, Silvia Ulrich, Malcolm Kohler, Marc J Poulin, Konrad E Bloch
BACKGROUND: Effects of hypobaric hypoxia at altitude on exercise performance of lowlanders with chronic obstructive pulmonary disease (COPD) have not been studied in detail. OBJECTIVES: To quantify changes in exercise performance and associated physiologic responses in lowlanders with COPD travelling to moderate altitude. METHODS: A total of 31 COPD patients with a median age (quartiles) of 66 years (59; 69) and FEV1 of 56% predicted (49; 69) living below 800 m performed a constant-load bicycle exercise to exhaustion at 60% of the maximal work rate at 490 m (Zurich) and at an identical work rate at 2,590 m (Davos) in randomized order...
March 2, 2018: Respiration; International Review of Thoracic Diseases
Melanie E Fields, Kristin P Guilliams, Dustin K Ragan, Michael M Binkley, Cihat Eldeniz, Yasheng Chen, Monica L Hulbert, Robert C McKinstry, Joshua S Shimony, Katie D Vo, Allan Doctor, Hongyu An, Andria L Ford, Jin-Moo Lee
OBJECTIVE: To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2 ) in children with SCD. METHODS: Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2 . An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps...
March 2, 2018: Neurology
Maria J Perez-Alvarez, Mario Villa Gonzalez, Irene Benito-Cuesta, Francisco G Wandosell
Intense efforts are being undertaken to understand the pathophysiological mechanisms triggered after brain ischemia and to develop effective pharmacological treatments. However, the underlying molecular mechanisms are complex and not completely understood. One of the main problems is the fact that the ischemic damage is time-dependent and ranges from negligible to massive, involving different cell types such as neurons, astrocytes, microglia, endothelial cells, and some blood-derived cells (neutrophils, lymphocytes, etc...
2018: Frontiers in Neuroscience
Denis E Bragin, Gloria L Statom, Edwin M Nemoto
OBJECTIVE: In previous work we showed that high intracranial pressure (ICP) in the rat brain induces a transition from capillary (CAP) to pathological microvascular shunt (MVS) flow, resulting in brain hypoxia, edema, and blood-brain barrier (BBB) damage. This transition was correlated with a loss of cerebral blood flow (CBF) autoregulation undetected by static autoregulatory curves but identified by induced dynamic ICP (iPRx) and cerebrovascular (iCVRx) reactivity. We hypothesized that loss of CBF autoregulation as correlated with MVS flow would be identified by iPRx and iCVRx in traumatic brain injury (TBI) with elevated ICP...
2018: Acta Neurochirurgica. Supplement
Denis E Bragin, Olga A Bragina, Sean Hagberg, Edwin M Nemoto
OBJECTIVE: High-frequency pulsed electromagnetic field (PEMF) stimulation is an emerging noninvasive therapy that we have shown increases cerebral blood flow (CBF) and tissue oxygenation in the healthy rat brain. In this work, we tested the effect of PEMF on the brain at high intracranial pressure (ICP). We previously showed that high ICP in rats caused a transition from capillary (CAP) to non-nutritive microvascular shunt (MVS) flow, tissue hypoxia and increased blood brain barrier (BBB) permeability...
2018: Acta Neurochirurgica. Supplement
Namitha Mohandas, Sebastian Bass-Stringer, Jovana Maksimovic, Kylie Crompton, Yuk J Loke, Janet Walstab, Susan M Reid, David J Amor, Dinah Reddihough, Jeffrey M Craig
Background: Cerebral palsy (CP) is a clinical description for a group of motor disorders that are heterogeneous with respect to causes, symptoms and severity. A diagnosis of CP cannot usually be made at birth and in some cases may be delayed until 2-3 years of age. This limits opportunities for early intervention that could otherwise improve long-term outcomes. CP has been recorded in monozygotic twins discordant for the disorder, indicating a potential role of non-genetic factors such as intrauterine infection, hypoxia-ischaemia, haemorrhage and thrombosis...
2018: Clinical Epigenetics
Vida Motamedi, Rebekah Kanefsky, Panagiotis Matsangas, Sara Mithani, Andreas Jeromin, Matthew S Brock, Vincent Mysliwiec, Jessica Gill
Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas that result in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules and, along with amyloid beta (Aβ), is associated with neurodegenerative processes. We sought to determine if tau and other biomarkers of inflammation were related to OSA severity. Concentrations of tau, Aβ40, Aβ42, c-reactive protein (CRP), TNF-α, interleukin (IL)-6, and IL-10 were measured in blood and compared between participants with moderate-severe OSA (n = 28), those with mild OSA (n = 22), and healthy controls (n = 24)...
March 2018: Sleep Medicine
Jian Yang, Cuiying Liu, Xiangnan Du, Menglei Liu, Xunming Ji, Huishan Du, Heng Zhao
BACKGROUND: Limb remote ischemic preconditioning (RIPC) protects against brain injury induced by stroke, but the underlying protective mechanisms remain unknown. As hypoxia inducible factor 1α (HIF-1α) is neuroprotective in stroke and mediates neuroinflammation, we tested the hypothesis that HIF-1α is a key factor of RIPC against stroke by mediating inflammation. METHODS AND RESULTS: Stroke was induced by transient middle cerebral artery occlusion in rats, and RIPC was conducted in both hind limbs...
February 24, 2018: Journal of the American Heart Association
Xiaoying Wu, Shengqun Liu, Zhenhua Hu, Guosong Zhu, Gaifang Zheng, Guangzhi Wang
Enriched environment (EE) has been shown to promote neurogenesis and functional recovery after ischemic stroke. However, the underlying molecular mechanisms are not fully understood. In this study, C57BL/6 mice underwent middle cerebral artery occlusion (60 minutes) followed by reperfusion, after which mice were housed in either standard environment (SE) or EE and allowed to survive for 3, 4, 6 or 10 weeks. Ipsilateral subventricular zone (SVZ) or striatum cells were dissociated from ischemic hemispheric brains of enriched mice at 14 days post-ischemia (dpi) and cultured in vitro...
February 22, 2018: Brain Research Bulletin
Ernesto Solis, Anum Afzal, Eugene A Kiyatkin
Oxycodone is a semi-synthetic opioid drug that is used to alleviate acute and chronic pain. However, oxycodone is often abused and, when taken at high doses, can induce powerful CNS depression that manifests in respiratory abnormalities, hypotension, coma, and death. Here, we employed several measurement techniques to examine the effects of intravenous oxycodone at a wide range of doses on various metabolism-related parameters in awake, freely-moving rats. High-speed amperometry was used to assess how oxycodone affects oxygen and glucose levels in the nucleus accumbens (NAc)...
February 21, 2018: Neuropharmacology
Monique Sieber, Jan Dreßler, Heike Franke, Dirk Pohlers, Benjamin Ondruschka
PURPOSE: Traumatic brain injury (TBI) is a very common entity that leads to numerous fatalities all over the world. Therefore, forensic pathologists are in desperate need of supplemental methodological tools for the diagnosis of TBI in everyday practice besides the standard autopsy. The present study determined post-mortem neuron specific enolase (NSE) and S100 calcium-binding protein B (S100B) levels as biological markers of an underlying TBI in autopsy cases. METHODS: Paired serum and CSF samples of 92 fatalities were collected throughout routine autopsies...
February 14, 2018: Journal of Forensic and Legal Medicine
Jason A Justice, Russell M Sanchez
Hypoxic-ischemic encephalopathy (HIE) refers to acute brain injury that results from perinatal asphyxia. HIE is a major cause of neonatal seizures, and outcomes can range from apparent recovery to severe cognitive impairment, cerebral palsy, and epilepsy. Acute partial seizures frequently aid in indicating the severity and localization of brain injury. However, evidence also suggests that the occurrence of seizures further increases the likelihood of epilepsy in later life regardless of the severity of the initial injury...
2018: Methods in Molecular Biology
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