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Stroke neuroprotective

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https://www.readbyqxmd.com/read/28637049/protecting-oligodendrocytes-by-targeting-non-glutamate-receptors-as-a-new-therapeutic-strategy-for-ischemic-stroke
#1
Pan Luo, Dong Liu, Lianjun Guo
Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons...
June 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28636928/neurovascular-toxicity-of-n-methyl-d-aspartate-is-markedly-enhanced-in-the-developing-mouse-central-nervous-system
#2
Sudhakar Vadivelu, Kui Xu, Vanja Tolj, Rahul Rege, Lindsay Darkins, Karthik Vishwanath
Penumbral perfusion is critical to brain viability. Proximal arterial occlusion and deep brain stroke has variable effect on cortical dysfunction. Cortical microvessel collaterals may be recruited and at times sufficient for partial parenchymal perfusion. Postnatal neural and endothelial cells are markedly vulnerable to glutamate excitotoxicity. Early vascular cell stress may promote partial protective neural preconditioning though postnatally a developmental window of the cerebral microvasculature may be particularly vulnerable to injury...
June 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28634570/to-use-or-not-to-use-metformin-in-cerebral-ischemia-a-review-of-the-application-of-metformin-in-stroke-rodents
#3
REVIEW
Isaac Arbeláez-Quintero, Mauricio Palacios
Ischemic strokes are major causes of death and disability. Searching for potential therapeutic strategies to prevent and treat stroke is necessary, given the increase in overall life expectancy. Epidemiological reports indicate that metformin is an oral antidiabetic medication that can reduce the incidence of ischemic events in patients with diabetes mellitus. Its mechanism of action has not been elucidated, but metformin pleiotropic effects involve actions in addition to glycemic control. AMPK activation has been described as one of the pharmacological mechanisms that explain the action of metformin and that lead to neuroprotective effects...
2017: Stroke Research and Treatment
https://www.readbyqxmd.com/read/28631089/targeted-temperature-management-in-the-icu-guidelines-from-a-french-expert-panel
#4
REVIEW
Alain Cariou, Jean-François Payen, Karim Asehnoune, Gerard Audibert, Astrid Botte, Olivier Brissaud, Guillaume Debaty, Sandrine Deltour, Nicolas Deye, Nicolas Engrand, Gilles Francony, Stéphane Legriel, Bruno Levy, Philippe Meyer, Jean-Christophe Orban, Sylvain Renolleau, Bernard Vigue, Laure De Saint Blanquat, Cyrille Mathien, Lionel Velly
Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method...
December 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28629519/erythropoietin-endogenous-protection-of-ischemic-brain
#5
Robert T Mallet, Myoung-Gwi Ryou
The human brain requires uninterrupted delivery of blood-borne oxygen and nutrients to sustain its function. Focal ischemia, particularly, ischemic stroke, and global ischemia imposed by cardiac arrest disrupt the brain's fuel supply. The resultant ATP depletion initiates a complex injury cascade encompassing intracellular Ca(2+) overload, glutamate excitotoxicity, oxido-nitrosative stress, extracellular matrix degradation, and inflammation, culminating in neuronal and astroglial necrosis and apoptosis, neurocognitive deficits, and even death...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28628913/age-dependent-effects-of-alk5-inhibition-and-mechanism-of-neuroprotection-in-neonatal-hypoxic-ischemic-brain-injury
#6
Brian H Kim, Mariano Guardia Clausi, Michelle Frondelli, Israel C Nnah, Chaitali Saqcena, Radek Dobrowolski, Steven W Levison
Neonatal encephalopathy due to hypoxic-ischemic (HI) brain injury triggers a wave of neuroinflammatory events attributed to causing the progressive degeneration and functional deficits seen weeks after the initial insult. In a recent set of studies, we evaluated the therapeutic efficacy of a small molecule antagonist for ALK5 (activin-like kinase 5 ), TGF-β receptor in a rat model of moderate perinatal HI and found significant improvements in neurologic outcomes. Here, we have extended those studies to evaluate the efficacy of delayed TGF-β receptor antagonism on postnatal day (P) 6 and P9 HI rat pups with and without hypothermia...
June 20, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28628214/unconventional-role-of-voltage-gated-proton-channels-vsop-hv1-in-regulation-of-microglial-ros-production
#7
Takafumi Kawai, Yoshifumi Okochi, Tomohiko Ozaki, Yoshio Imura, Schuichi Koizumi, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Toshihide Yamashita, Yasushi Okamura
It has been established that voltage-gated proton channels (VSOP/Hv1), encoded by Hvcn1, support reactive oxygen species (ROS) production in phagocytic activities of neutrophils (El Chemaly et al. 2010) and antibody production in B lymphocytes (Capasso et al. 2010). VSOP/Hv1 is a potential therapeutic target for brain ischemia, since Hvcn1 deficiency reduces microglial ROS production and protects brain from neuronal damage (Wu et al. 2012). In the present study, we report that VSOP/Hv1 has paradoxical suppressive role in ROS production in microglia...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28625785/cerebral-ischemia-repefusion-injury-from-bench-space-to-bedside
#8
REVIEW
Z Nagy, S Nardai
While stroke research represents the primary interface between circulation and brain research, the hemostasis system also carries a pivotal role in the mechanism of vascular brain injury. The complex interrelated events triggered by the energy crisis have a specific spatial and temporal pattern arching from the initial damage to the final events of brain repair. The complexity of the pathophysiology make it difficult to model this disease, therefore it is challenging to find appropriate therapeutic targets...
June 15, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28624878/a-combination-of-three-repurposed-drugs-administered-at-reperfusion-as-a-promising-therapy-for-postischemic-brain-injury
#9
I-Chen Yu, Ping-Chang Kuo, Jui-Hung Yen, Hallel C Paraiso, Eric T Curfman, Benecia C Hong-Goka, Robert D Sweazey, Fen-Lei Chang
Cerebral ischemia leads to multifaceted injury to the brain. A polytherapeutic drug that can be administered immediately after reperfusion may increase protection to the brain by simultaneously targeting multiple deleterious cascades. This study evaluated efficacy of the combination of three clinically approved drugs: lamotrigine, minocycline, and lovastatin, using two mouse models: global and focal cerebral ischemia induced by transient occlusion of the common carotid arteries or the middle cerebral artery, respectively...
June 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28620235/a-non-ionotropic-activity-of-nmda-receptors-contributes-to-glycine-induced-neuroprotection-in-cerebral-ischemia-reperfusion-injury
#10
Juan Chen, Rong Hu, Huabao Liao, Ya Zhang, Ruixue Lei, Zhifeng Zhang, Yang Zhuang, Yu Wan, Ping Jin, Hua Feng, Qi Wan
NMDA receptor (NMDAR) is known for its ionotropic function. But recent evidence suggests that NMDAR also has a non-ionotropic property. To determine the role of non-ionotropic activity of NMDARs in clinical relevant conditions, we tested the effect of glycine, a co-agonist of NMDARs, in rat middle cerebral artery occlusion (MCAO), an animal model of cerebral ischemia-reperfusion injury after the animals were injected with the NMDAR channel blocker MK-801 and the glycine receptor antagonist strychnine. We show that glycine reduces the infarct volume in the brain of ischemic stroke animals pre-injected with MK-801 and strychnine...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617387/-pharmacological-neuroprotection-in-stroke-in-clinical-practice-new-perspectives
#11
D V Sergeev, M A Domashenko, M A Piradov
Despite recent advances in acute stroke care, clinical armamentarium against stroke remains limited. Furthermore, highly effective approaches to stroke treatment, such as systemic reperfusion and mechanical thrombectomy, cannot be performed in the majority of patients. Neuroprotective strategies, i.e. prevention of irreversible cell damage due to the ischemia, may improve stroke outcomes. However, only few pharmacological agents demonstrated clinical efficacy. Citicoline is an endogenous mononucleotide with neuroprotective effect and established clinical safety and tolerability, which effectiveness in acute stroke was studied in several large, well-controlled trials...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28617376/-postoperative-cerebral-dysfunction
#12
N V Tsygan, M M Odinak, G G Khubulava, V N Tsygan, A S Peleshok, R V Andreev, E S Kurasov, I V Litvinenko
AIM: To study the structure, risk factors and methods of prevention of postoperative brain dysfunction on the example of coronary artery bypass surgery with cardiopulmonary bypass. MATERIAL AND METHODS: The study included 77 patients who undergone elective coronary artery bypass surgery at the beating heart (22 patients) or with cardiopulmonary bypass (55 patients, including 24 patients, who received cerebroprotective treatment with cytoflavin in the preoperative period)...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28617078/interplay-between-notch-and-p53-promotes-neuronal-cell-death-in-ischemic-stroke
#13
Priyanka Balaganapathy, Sang-Ha Baik, Karthik Mallilankaraman, Christopher G Sobey, Dong-Gyu Jo, Thiruma V Arumugam
Stroke is the world's second leading cause of mortality, with a high incidence of morbidity. Numerous neuronal membrane receptors are activated by endogenous ligands and may contribute to infarct development. Notch is a well-characterized membrane receptor involved in cell differentiation and proliferation, and now shown to play a pivotal role in cell death during ischemic stroke. Blockade of Notch signaling by inhibition of γ-secretase, an enzyme that generates the active form of Notch, is neuroprotective following stroke...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28615451/molecular-mechanisms-of-signaling-via-the-docosanoid-neuroprotectin-d1-for-cellular-homeostasis-and-neuroprotection
#14
Aram Asatryan, Nicolas G Bazan
Docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member that is enriched in the nervous system, generates bioactive docosanoids that can counteract disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimers disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-kappaB subtype that, in turn, enhances expression of BIRC3 (baculoviral IAP repeat-containing protein 3, or cIAP2) in retinal cells...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28611572/4r-cembranoid-improves-outcomes-after-6-hydroxydopamine-challenge-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#15
Jing Hu, P A Ferchmin, Ann M Hemmerle, Kim B Seroogy, Vesna A Eterovic, Jiukuan Hao
(1S, 2E, 4R, 6R,-7E, 11E)-2, 7, 11-cembratriene-4, 6-diol (4R) is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA) and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP). Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD) and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA)-induced injury models...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28611085/ccr6-cc-chemokine-receptor-6-is-essential-for-the-migration-of-detrimental-natural-interleukin-17-producing-%C3%AE-%C3%AE-t-cells-in-stroke
#16
Priyadharshini Arunachalam, Peter Ludewig, Patrick Melich, Thiruma Valavan Arumugam, Christian Gerloff, Immo Prinz, Tim Magnus, Mathias Gelderblom
BACKGROUND AND PURPOSE: Immune-mediated tissue damage after stroke evolves within the first days, and lymphocytes contribute to the secondary injury. Our goal was to identify T-cell subpopulations, which trigger the immune response. METHODS: In a model of experimental stroke, we analyzed the immune phenotype of interleukin-17 (IL-17)-producing γδ T cells and explored the therapeutic potential of neutralizing anti-IL-17 antibodies in combination with mild therapeutic hypothermia...
June 13, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28609577/cerebrolysin-prevents-deficits-in-social-behavior-repetitive-conduct-and-synaptic-inhibition-in-a-rat-model-of-autism
#17
Roberto Cuevas-Olguin, Swagata Roychowdhury, Anwesha Banerjee, Francisco Garcia-Oscos, Eric Esquivel-Rendon, María Elena Bringas, Michael P Kilgard, Gonzalo Flores, Marco Atzori
Autism spectrum disorder (ASD) is a syndrome of diverse neuropsychiatric diseases of growing incidence characterized by repetitive conduct and impaired social behavior and communication for which effective pharmacological treatment is still unavailable. While the mechanisms and etiology of ASD are still unknown, a consensus is emerging about the synaptic nature of the syndrome, suggesting a possible avenue for pharmacological treatment with synaptogenic compounds. The peptidic mixture cerebrolysin (CBL) has been successfully used during the last three decades in the treatment of stroke and neurodegenerative disease...
June 13, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28608237/exogenous-adipokine-peptide-resistin-protects-against-focal-cerebral-ischemia-reperfusion-injury-in-mice
#18
Jiangtao Zhu, Di Wu, Chenyu Zhao, Man Luo, Ronald C Hamdy, Balvin H L Chua, Xingshun Xu, Zhigang Miao
Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28608001/anti-zn-2-toxicity-of-4-hydroxybenzyl-alcohol-in-astrocytes-and-neurons-contribute-to-a-robust-neuroprotective-effects-in-the-postischemic-brain
#19
Lidan Luo, Seung-Woo Kim, Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Ja-Kyeong Lee
4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn(2+) toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects...
June 12, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28607351/early-oxygen-therapy-does-not-protect-the-brain-from-vasogenic-edema-following-acute-ischemic-stroke-in-adult-male-rats
#20
Elmira Pasban, Hamdollah Panahpour, Akbar Vahdati
Brain edema aggravates primary brain injury and increases its mortality rate after ischemic stroke. It is believed that normobaric oxygen therapy (NBO) may produce neuroprotective effects against ischemic stroke; however, reports have been controversial, and its effects on vasogenic brain edema as a major complication of brain ischemia have not been clarified. The present study investigates the effects of NBO on cerebral edema and blood - brain barrier integrity using rat model of ischemic stroke. Transient focal cerebral ischemia was induced in adult male Sprague-Dawley rats by left middle cerebral artery occlusion (MCAO) for 90 min followed by 24 h reperfusion...
June 12, 2017: Scientific Reports
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