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Neuroprotection

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https://www.readbyqxmd.com/read/28651232/silymarin-prevents-nlrp3-inflammasome-activation-and-protects-against-intracerebral-hemorrhage
#1
Raorao Yuan, Hengyi Fan, Shiqi Cheng, WeiWei Gao, Xin Xu, Shigang Lv, Minhua Ye, Miaojing Wu, Xingen Zhu, Yan Zhang
Inflammatory response mediates secondary injury during intracerebral hemorrhage (ICH). In the present study, we determined oxidative stress and involvement of NLRP3 in ICH injury and analyzed whether silymarin might offer protective effect against ICH injury. Post 24h after ICH injury there was increased oxidative stress markers (reactive oxygen species (ROS) and lipid peroxides) compared to sham group. Silymarin (200mg/kg) treatment 30 mins post ICH injury prevented increase in oxidative stress markers and up-regulated antioxidant status...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28651064/progranulin-as-a-biomarker-and-potential-therapeutic-agent
#2
REVIEW
Vanessa Abella, Jesús Pino, Morena Scotece, Javier Conde, Francisca Lago, Miguel Angel Gonzalez-Gay, Antonio Mera, Rodolfo Gómez, Ali Mobasheri, Oreste Gualillo
Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration. In this review, we summarise the most recent research advances concerning the potential role of progranulin as a therapeutic target and biomarker in cancer, neurodegenerative and inflammatory diseases...
June 23, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28650631/effect-of-the-biphenyl-neolignan-honokiol-on-a%C3%AE-42-induced-toxicity-in-caenorhabditis-elegans-a%C3%AE-42-fibrillation-cholinesterase-activity-dpph-radicals-and-iron-ii-chelation
#3
Srinivas Kantham, Stephen Chan, Gawain McColl, Jared Miles, Suresh Kumar Veliyath, Girdhar Singh Deora, Satish N Dighe, Samira Khabbazi, Marie-Odile Parat, Benjamin P Ross
The biphenyl neolignan honokiol is a neuroprotectant which has been proposed as a treatment for central nervous system disorders such as Alzheimer's disease (AD). The death of cholinergic neurons in AD is attributed to multiple factors, including: accumulation and fibrillation of amyloid beta peptide (Aβ) within the brain; metal ion toxicity; and oxidative stress. In this study, we used a transgenic Caenorhabditis elegans model expressing full length Aβ42 as a convenient in vivo system for examining the effect of honokiol against Aβ-induced toxicity...
June 26, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28650361/pharmacological-thromboembolic-prophylaxis-in-traumatic-brain-injuries-low-molecular-weight-heparin-is-superior-to-unfractionated-heparin
#4
Elizabeth Benjamin, Gustavo Recinos, Alberto Aiolfi, Kenji Inaba, Demetrios Demetriades
OBJECTIVE: We hypothesized that low molecular weight heparin (LMWH) is superior to unfractionated heparin (UH) for venous thromboembolism (VTE) prophylaxis in patients with severe traumatic brain injuries (TBI). SUMMARY BACKGROUND DATA: Pharmacological VTE prophylaxis with LMWH or UH is the current standard of care in TBI. Clinical work suggests that LMWH may be more effective than UH for VTE prophylaxis in trauma patients. Experimental work shows that heparinoids may have neuroprotective properties...
June 22, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28650095/sex-differences-in-brain-mitochondrial-metabolism-influence-of-endogenous-steroids-and-stroke
#5
REVIEW
P Gaignard, M Fréchou, P Liere, P Thérond, M Schumacher, A Slama, R Guennoun
Steroids are neuroprotective and growing body of evidence indicates that mitochondria are a potential target of their effects. The mitochondria are the site of cellular energy synthesis, regulate oxidative stress and play a key role in cell death after brain injury and neurodegenerative diseases. After a summary of the literature on the general functions of mitochondria and the effects of sex steroid administrations on mitochondrial metabolism, we will summarize and discuss our recent findings concerning sex differences in brain mitochondrial function in physiological and pathological conditions...
June 26, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28649610/evaluation-of-the-safety-and-immunomodulatory-effects-of-sargramostim-in-a-randomized-double-blind-phase-1-clinical-parkinson-s-disease-trial
#6
Howard E Gendelman, Yuning Zhang, Pamela Santamaria, Katherine E Olson, Charles R Schutt, Danish Bhatti, Bhagya Laxmi Dyavar Shetty, Yaman Lu, Katherine A Estes, David G Standaert, Elizabeth Heinrichs-Graham, LuAnn Larson, Jane L Meza, Matthew Follett, Erica Forsberg, Gary Siuzdak, Tony W Wilson, Carolyn Peterson, R Lee Mosley
A potential therapeutic role for immune transformation in Parkinson's disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson's disease patients...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28649223/pretreatment-with-sodium-phenylbutyrate-alleviates-cerebral-ischemia-reperfusion-injury-by-upregulating-dj-1-protein
#7
Rui-Xin Yang, Jie Lei, Bo-Dong Wang, Da-Yun Feng, Lu Huang, Yu-Qian Li, Tao Li, Gang Zhu, Chen Li, Fang-Fang Lu, Tie-Jian Nie, Guo-Dong Gao, Li Gao
Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28649222/highly-selective-cyclooxygenase-1-inhibitors-p6-and-mofezolac-counteract-inflammatory-state-both-in-vitro-and-in-vivo-models-of-neuroinflammation
#8
Rosa Calvello, Dario Domenico Lofrumento, Maria Grazia Perrone, Antonia Cianciulli, Rosaria Salvatore, Paola Vitale, Francesco De Nuccio, Laura Giannotti, Giuseppe Nicolardi, Maria Antonietta Panaro, Antonio Scilimati
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28649199/glyx-13-a-nmda-receptor-glycine-site-functional-partial-agonist-attenuates-cerebral-ischemia-injury-in-vivo-and-vitro-by-differential-modulations-of-nmda-receptors-subunit-components-at-different-post-ischemia-stage-in-mice
#9
Chen Zheng, Zhi H Qiao, Meng Z Hou, Nan N Liu, Bin Fu, Ran Ding, Yuan Y Li, Liang P Wei, Ai L Liu, Hui Shen
Excessive activation of NMDA receptors (NMDARs) is implicated in pathological synaptic plasticity also known as post-ischemic long-term potentiation (i-LTP) which was produced by glutamate mediated excitotoxicity after stroke. In the past decades, many NMDARs inhibitors failed in clinical investigations due to severe psychotomimetic side effects. GLYX-13 is a NMDAR modulator with glycine site partial agonist properties and has potential protective effects on ischemic neuronal death. However, the underlying molecular mechanism of GLYX-13 attenuating the ischemic neuronal damage remains elusive...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28648945/phosphodiesterase-5-inhibition-as-a-therapeutic-target-for-ischemic-stroke-a-systematic-review-of-preclinical-studies
#10
Joakim N E Ölmestig, Ida R Marlet, Atticus H Hainsworth, Christina Kruuse
Phosphodiesterase 5 inhibitors (PDE5i), such as sildenafil (Viagra®) are widely used for erectile dysfunction and pulmonary hypertension. Preclinical studies suggest that PDE5i may improve functional outcome following ischemic stroke. In this systematic review we aimed to evaluate the effects of selective PDE5i in animal models of brain ischaemia. A systematic search in Medline, Embase, and The Cochrane Library was performed including studies in English assessing the effects of selective PDE5i. 32 publications were included describing outcome in 3646 animals...
June 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28648389/stress-primes-microglial-polarization-after-global-ischemia-therapeutic-potential-of-progesterone
#11
Claudia Espinosa-Garcia, Iqbal Sayeed, Seema Yousuf, Fahim Atif, Elena G Sergeeva, Gretchen N Neigh, Donald G Stein
Despite the fact stress is associated with increased risk of stroke and worsened outcome, most preclinical studies have ignored this comorbid factor, especially in the context of testing neuroprotective treatments. Preclinical research suggests that stress primes microglia, resulting in an enhanced reactivity to a subsequent insult and potentially increasing vulnerability to stroke. Ischemia-induced activated microglia can be polarized into a harmful phenotype, M1, which produces pro-inflammatory cytokines, or a protective phenotype, M2, which releases anti-inflammatory cytokines and neurotrophic factors...
June 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28647597/hypoxic-postconditioning-improves-behavioural-deficits-at-6-weeks-following-hypoxic-ischemic-brain-injury-in-neonatal-rats
#12
Jonathan D Teo, Margaret J Morris, Nicole M Jones
Hypoxic-ischemic (HI) brain injury in newborns is associated with high morbidity and mortality, with many babies suffering neurological deficits. Recently, we showed that hypoxic postconditioning (PostC) immediately post injury can protect against HI up to one week in neonatal rats. Here, we aimed to examine whether long term functional deficits were also improved by PostC. Sprague-Dawley rats were assigned to control (C) or HI group on postnatal day 7 (P7). The HI group underwent unilateral carotid artery occlusion followed by hypoxia (7% oxygen, 3h)...
June 21, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28647536/crhr1-exacerbates-the-glial-inflammatory-response-and-alters-bdnf-trkb-pcreb-signaling-in-a-rat-model-of-global-cerebral-ischemia-implications-for-neuroprotection-and-cognitive-recovery
#13
Patricia B de la Tremblaye, Simon M Benoit, Sarah Schock, Hélène Plamondon
This study examined the impact of corticotropin-releasing hormone type 1 receptor (CRHR1) blockade using Antalarmin (ANT) on the expression of markers of neuroplasticity and inflammation, as well as neuroprotection and behavioral recovery following global cerebral ischemia. Male Wistar rats (N=50) were treated with ANT (2μg/2μl; icv) or a vehicle solution prior to a sham or four vessel (4VO) occlusion. Seven days post ischemia, anxiety was assessed in the Elevated Plus Maze and Open Field tests, and fear and spatial learning in a Y-Maze Passive Avoidance Task and the Barnes Maze...
June 21, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28647405/docosahexaenoic-acid-promotes-oligodendrocyte-differentiation-via-ppar-%C3%AE-signalling-and-prevents-tumor-necrosis-factor-%C3%AE-dependent-maturational-arrest
#14
A Bernardo, M L Giammarco, C De Nuccio, M A Ajmone-Cat, S Visentin, R De Simone, L Minghetti
Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid known to be neuroprotective in several models of human diseases, including multiple sclerosis. The protective effects of DHA are largely attributed to its ability to interfere with the activity of transcription factors controlling immune and inflammatory responses, including the agonist-dependent transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). In this study, we used primary oligodendrocyte progenitor (OP) cultures from neonatal rat brain to investigate whether DHA could influence OP maturation and directly promote myelination, as previously reported for selective PPAR-γ agonists...
June 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28647375/type-i-interferon-signalling-through-ifnar1-plays-a-deleterious-role-in-the-outcome-after-stroke
#15
Moses Zhang, Catherine E Downes, Connie H Y Wong, Kate M Brody, Pedro L Guio-Agulair, Jodee Gould, Robert Ates, Paul J Hertzog, Juliet M Taylor, Peter J Crack
Neuroinflammation contributes significantly to the pathophysiology of stroke. Here we test the hypothesis that the type I interferon receptor (IFNAR1) plays a critical role in neural injury after stroke by regulating the resultant pro-inflammatory environment. Wild-type and IFNAR1(-/-) primary murine neurons and glia were exposed to oxygen glucose deprivation (OGD) and cell viability was assessed. Transient cerebral ischemia/reperfusion injury was induced by mid-cerebral artery occlusion (MCAO) in wild-type and IFNAR1(-/-) and IFNAR2(-/-) mice in vivo, and infarct size, and molecular parameters measured...
June 21, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28647363/cadps2-gene-expression-is-oppositely-regulated-by-lrrk2-and-alpha-synuclein
#16
Julia Obergasteiger, Christa Überbacher, Peter P Pramstaller, Andrew A Hicks, Corrado Corti, Mattia Volta
The Ca(2+)-dependent activator protein for secretion 2 (CADPS2) is a member of the CAPS/CADPS protein family that play crucial roles in synaptic vesicle dynamics. Genomic variability in the CADPS2 gene has been associated to autism spectrum disorders and Alzheimer's disease, both characterized by altered neurotransmission. Biological evidence also linked CADPS2 to Parkinson's disease (PD), as a disease-causing mutation in leucine-rich repeat kinase 2 (LRRK2) was reported to increase CADPS2 gene and protein expression...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28646880/6-shogaol-a-neuroactive-compound-of-ginger-jahe-gajah-induced-neuritogenic-activity-via-ngf-responsive-pathways-in-pc-12-cells
#17
Syntyche Ling Sing Seow, Sok Lai Hong, Guan Serm Lee, Sri Nurestri Abd Malek, Vikineswary Sabaratnam
BACKGROUND: Ginger is a popular spice and food preservative. The rhizomes of the common ginger have been used as traditional medicine to treat various ailments. 6-Shogaol, a pungent compound isolated from the rhizomes of jahe gajah (Zingiber officinale var officinale) has shown numerous pharmacological activities, including neuroprotective and anti-neuroinflammatory activities. The aim of this study was to investigate the potential of 6-shogaol to mimic the neuritogenic activity of nerve growth factor (NGF) in rat pheochromocytoma (PC-12) cells...
June 24, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28646450/microrna-changes-in-preconditioning-induced-neuroprotection
#18
REVIEW
Josh D Bell, Jang-Eun Cho, Rona G Giffard
Preconditioning is a paradigm in which sublethal stress-prior to a more injurious insult-induces protection against injury. In the central nervous system (CNS), preconditioning against ischemic stroke is induced by short durations of ischemia, brief seizures, exposure to anesthetics, and other stresses. Increasing evidence supports the contribution of microRNAs (miRNAs) to the pathogenesis of cerebral ischemia and ischemic tolerance induced by preconditioning. Studies investigating miRNA changes induced by preconditioning have to date identified 562 miRNAs that change expression levels after preconditioning, and 15% of these changes were reproduced in at least one additional study...
June 23, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28646409/neuroprotective-effects-of-g-csf-administration-in-microglia-mediated-reactive-t-cell-activation-in-vitro
#19
Wei Peng
G-CSF is a growth factor that has known neuroprotective effects in a variety of experimental brain injury models. As both antigen-presenting microglia and reactive T cells are key components in the development and progression of EAE, the aim of this study is to investigate the neuroprotective effects of recombinant human G-CSF, as administered in microglia-mediated reactive T cell assay in vitro. Our results indicate that G-CSF treatment has no apparent effect for the resting un-activated microglia. G-CSF pre-protection of microglia increased protective cytokine IL-4 production and effectively inhibited the productions of NO and other inflammatory mediators (IFN-γ, TNF-α, IL-1β, IL-17, and chemokine MCP-1) after LPS stimulation...
June 23, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28646259/chronic-administration-of-s-allylcysteine-activates-nrf2-factor-and-enhances-the-activity-of-antioxidant-enzymes-in-the-striatum-frontal-cortex-and-hippocampus
#20
Úrzula Franco-Enzástiga, Ricardo A Santana-Martínez, Carlos A Silva-Islas, Diana Barrera-Oviedo, María Elena Chánez-Cárdenas, Perla D Maldonado
Oxidative stress plays an important role in neurodegenerative diseases and aging. The cellular defense mechanisms to deal with oxidative damage involve the activation of transcription factor related to NF-E2 (Nrf2), which enhances the transcription of antioxidant and phase II enzyme genes. S-allylcysteine (SAC) is an antioxidant with neuroprotective properties, and the main organosulfur compound in aged garlic extract. The ability of SAC to activate the Nrf2 factor has been previously reported in hepatic cells; however this effect has not been studied in normal brain...
June 24, 2017: Neurochemical Research
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