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https://www.readbyqxmd.com/read/28535416/the-role-of-timing-in-the-treatment-of-spinal-cord-injury
#1
REVIEW
Amene Saghazadeh, Nima Rezaei
Regeneration failure after primary spinal cord injury (SCI) leads to diverse clinical complications in a severity- and level of SCI-dependent manner. The cost of treating both of them (initial regeneration failure and following complications) would be prohibitive, particularly in less developed nations. The well-recognized circumstances arose from primary SCI include excitotoxicity and inflammation. SCI increases concentrations of extracellular amino acids (EAAs) in the severity-dependent manner and the maximum level of EAAs at the injury site will be reduced by distance from the injury site...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28534662/neuroprotection-of-brain-permeable-iron-chelator-vk-28-against-intracerebral-hemorrhage-in-mice
#2
Qian Li, Jieru Wan, Xi Lan, Xiaoning Han, Zhongyu Wang, Jian Wang
Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28533375/keap1-modifying-small-molecule-reveals-muted-nrf2-signaling-responses-in-neural-stem-cells-from-huntington-s-disease-patients
#3
Luisa Quinti, Sharadha Dayalan Naidu, Ulrike Träger, Xiqun Chen, Kimberly Kegel-Gleason, David Llères, Colúm Connolly, Vanita Chopra, Cho Low, Sébastien Moniot, Ellen Sapp, Adelaide R Tousley, Petr Vodicka, Michael J Van Kanegan, Linda S Kaltenbach, Lisa A Crawford, Matthew Fuszard, Maureen Higgins, James R C Miller, Ruth E Farmer, Vijay Potluri, Susanta Samajdar, Lisa Meisel, Ningzhe Zhang, Andrew Snyder, Ross Stein, Steven M Hersch, Lisa M Ellerby, Eranthie Weerapana, Michael A Schwarzschild, Clemens Steegborn, Blair R Leavitt, Alexei Degterev, Sarah J Tabrizi, Donald C Lo, Marian DiFiglia, Leslie M Thompson, Albena T Dinkova-Kostova, Aleksey G Kazantsev
The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28527714/investigation-of-left-and-right-lateral-fluid-percussion-injury-in-c57bl6-j-mice-in-vivo-functional-consequences
#4
Lesley D Schurman, Terry L Smith, Anthony J Morales, Nancy N Lee, Thomas M Reeves, Linda L Phillips, Aron H Lichtman
Although rodent models of traumatic brain injury (TBI) reliably produce cognitive and motor disturbances, behavioral characterization resulting from left and right hemisphere injuries remains unexplored. Here we examined the functional consequences of targeting the left versus right parietal cortex in lateral fluid percussion injury, on Morris water maze (MWM) spatial memory tasks (fixed platform and reversal) and neurological motor deficits (neurological severity score and rotarod). In the MWM fixed platform task, right lateral injury produced a small delay in acquisition rate compared to left...
May 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28526411/jnj10181457-a-histamine-h3-receptor-inverse-agonist-regulates-in-vivo-microglial-functions-and-improves-depression-like-behaviours-in-mice
#5
Tomomitsu Iida, Takeo Yoshikawa, Anikó Kárpáti, Takuro Matsuzawa, Haruna Kitano, Asuka Mogi, Ryuichi Harada, Fumito Naganuma, Tadaho Nakamura, Kazuhiko Yanai
Brain histamine acts as a neurotransmitter and regulates various physiological functions, such as learning and memory, sleep-wake cycles, and appetite regulation. We have recently shown that histamine H3 receptor (H3R) is expressed in primary mouse microglia and has a strong influence on critical functions in microglia, including chemotaxis, phagocytosis, and cytokine secretion in vitro. However, the importance of H3R in microglial activity in vivo remains unknown. Here, we examined the effects of JNJ10181457 (JNJ), a selective and potent H3R inverse agonist, on microglial functions ex vivo and in vivo...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28524175/modulators-of-microglial-activation-and-polarization-after-intracerebral-haemorrhage
#6
REVIEW
Xi Lan, Xiaoning Han, Qian Li, Qing-Wu Yang, Jian Wang
Intracerebral haemorrhage (ICH) is the most lethal subtype of stroke but currently lacks effective treatment. Microglia are among the first non-neuronal cells on the scene during the innate immune response to ICH. Microglia respond to acute brain injury by becoming activated and developing classic M1-like (proinflammatory) or alternative M2-like (anti-inflammatory) phenotypes. This polarization implies as yet unrecognized actions of microglia in ICH pathology and recovery, perhaps involving microglial production of proinflammatory or anti-inflammatory cytokines and chemokines...
May 19, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28523372/dietary-eicosapentaenoic-acid-normalizes-hippocampal-omega-3-and-6-polyunsaturated-fatty-acid-profile-attenuates-glial-activation-and-regulates-bdnf-function-in-a-rodent-model-of-neuroinflammation-induced-by-central-interleukin-1%C3%AE-administration
#7
Yilong Dong, Min Xu, Allan V Kalueff, Cai Song
PURPOSE: Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer's disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear...
May 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28523230/targeting-resolution-of-neuroinflammation-after-ischemic-stroke-with-a-lipoxin-a4-analog-protective-mechanisms-and-long-term-effects-on-neurological-recovery
#8
Kimberly E Hawkins, Kelly M DeMars, Jon C Alexander, Lauren G de Leon, Sean C Pacheco, Christina Graves, Changjun Yang, Austin O McCrea, Jan C Frankowski, Timothy J Garrett, Marcelo Febo, Eduardo Candelario-Jalil
BACKGROUND: Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti-inflammatory, pro-resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML-111. We hypothesized that post-ischemic, intravenous treatment with BML-111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats...
May 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28522972/recent-advances-in-the-study-of-bipolar-rod-shaped-microglia-and-their-roles-in-neurodegeneration
#9
Ngan Pan Bennett Au, Chi Him Eddie Ma
Microglia are the resident immune cells of the central nervous system (CNS) and they contribute to primary inflammatory responses following CNS injuries. The morphology of microglia is closely associated with their functional activities. Most previous research efforts have attempted to delineate the role of ramified and amoeboid microglia in the pathogenesis of neurodegenerative diseases. In addition to ramified and amoeboid microglia, bipolar/rod-shaped microglia were first described by Franz Nissl in 1899 and their presence in the brain was closely associated with the pathology of infectious diseases and sleeping disorders...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28521131/diverse-requirements-for-microglial-survival-specification-and-function-revealed-by-defined-medium-cultures
#10
Christopher J Bohlen, F Chris Bennett, Andrew F Tucker, Hannah Y Collins, Sara B Mulinyawe, Ben A Barres
Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28519900/type-i-interferon-pathway-in-cns-homeostasis-and-neurological-disorders
#11
REVIEW
Thomas Blank, Marco Prinz
Type I interferons (IFNs), IFN-α and IFN-β, represent the major effector cytokines of the host immune response against viruses and other intracellular pathogens. These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll-like receptor signaling network, retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS)...
May 18, 2017: Glia
https://www.readbyqxmd.com/read/28516431/a-comparison-of-neuroimaging-abnormalities-in-multiple-sclerosis-major-depression-and-chronic-fatigue-syndrome-myalgic-encephalomyelitis-is-there-a-common-cause
#12
REVIEW
Gerwyn Morris, Michael Berk, Basant K Puri
There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28514764/trim32-affects-the-recovery-of-motor-function-following-spinal-cord-injury-through-regulating-proliferation-of-glia
#13
Qiang Fu, Ming-Ming Zou, Jian-Wei Zhu, Yan Zhang, Wen-Jin Chen, Mei Cheng, Chun-Feng Liu, Quan-Hong Ma, Ru-Xiang Xu
Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit the axonal regeneration after spinal cord injury (SCI). However, the underlying molecular mechanisms remain unclear. In the present study, we identify tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in glial cells in the normal uninjured spinal cord, exhibits strong expression in both astrocytes and microglia following SCI. We further observe that deficiency of TRIM32 results in increased numbers of astrocytes and microglia, which is accompanied by enhanced proliferation of both cells and increased secretion of interleukin (IL)-1 and IL-10...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28510630/local-and-systemic-inflammatory-biomarkers-of-diabetic-retinopathy-an-integrative-approach
#14
Stela Vujosevic, Rafael Simó
Purpose: To review the usefulness of local and systemic inflammatory biomarkers of diabetic retinopathy (DR) to implement a more personalized treatment. Methods: An integrated research (from ophthalmologist and diabetologist point of view) of most significant literature on serum, vitreous, and aqueous humor (AH) biochemical biomarkers related to inflammation at early and advanced stages of DR (including diabetic macular edema [DME] and proliferative DR) was performed...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28508449/satellite-glial-cells-in-human-trigeminal-ganglia-have-a-broad-expression-of-functional-toll-like-receptors
#15
Johanna G Mitterreiter, Werner J D Ouwendijk, Monique van Velzen, Gijsbert P van Nierop, Albert D M E Osterhaus, Georges M G M Verjans
Toll-like receptors (TLRs) orchestrate immune responses to a wide variety of danger- and pathogen-associated molecular patterns. Compared to the central nervous system (CNS), expression profile and function of TLRs in the human peripheral nervous system (PNS) are ill-defined. We analyzed TLR expression of satellite glial cells (SGCs) and microglia, glial cells predominantly involved in local immune responses in ganglia of the human PNS and normal-appearing white matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed that both SGCs and microglia expressed TLR1-5, TLR7 and TLR9, although expression levels varied between these cell types...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28508368/de-novo-and-uninterrupted-silac-labeling-of-primary-microglia
#16
Ping Zhang, Ashley Culver-Cochran, Stanley M Stevens, Bin Liu
Microglia have increasingly been recognized as playing a wide spectrum of roles in various physiological and pathological processes in the central nervous system. Studies in the past have mostly associated individual microglial enzymes or soluble factors such as cytokines with specific functions of microglia. Stable isotope labeling with amino acids in cell culture (SILAC)-based proteomic analysis enables an unbiased, simultaneous, and global-scale analysis of the expression of thousands of proteins involved in key cellular pathways that regulate microglial activities...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28508173/neuroprotective-effects-of-lycium-barbarum-polysaccharide-on-focal-cerebral-ischemic-injury-in-mice
#17
Peng Zhao, Ru Zhou, Xiao-Yun Zhu, Gang Liu, Yu-Ping Zhao, Peng-Sheng Ma, Wei Wu, Yang Niu, Tao Sun, Yu-Xiang Li, Jian-Qiang Yu, Zhong-Ming Qian
Increasing evidence demonstrates inflammation contributes to neuronal death following cerebral ischemia. Lycium barbarum polysaccharide (LBP) has been reported to prevent scopolamine-induced cognitive and memory deficits. We recently indicated that LBP exerts neuroprotective effect against focal cerebral ischemic injury in mice via attenuating the mitochondrial apoptosis pathway. The aim of this study was to investigate the neuroprotective effects of LBP against the behavioral dysfunction induced by focal cerebral ischemia injury in mice...
May 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28503634/an-acute-mouse-spinal-cord-slice-preparation-for-studying-glial-activation-ex-vivo
#18
Juan Mauricio Garré, Guang Yang, Feliksas F Bukauskas, Michael V L Bennett
Pathological conditions such as amyotrophic lateral sclerosis, spinal cord injury and chronic pain are characterized by activation of astrocytes and microglia in spinal cord and have been modeled in rodents. In vivo imaging at cellular level in these animal models is limited due to the spinal cord's highly myelinated funiculi. The preparation of acute slices may offer an alternative and valuable strategy to collect structural and functional information in vitro from dorsal, lateral and ventral regions of spinal cord...
January 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28501776/inhibition-of-senp3-by-urb597-ameliorates-neurovascular-unit-dysfunction-in-rats-with-chronic-cerebral-hypoperfusion
#19
Da-Peng Wang, Ke-Jia Liu, Graham Kasper, Qi Lin, Jian Hai
Disruption of the neurovascular unit (NVU), induced by chronic cerebral hypoperfusion (CCH), has been broadly found in various neurological disorders. SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and microglia, and regulates a variety of cell events. However, whether SENP3 is involved in neurovascular injury under the condition of CCH is still elusive. To address this issue, we investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as the underling mechanisms...
May 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28499970/chitinase1-contributed-to-a-potential-protection-via-microglia-polarization-and-a%C3%AE-oligomer-reduction-in-d-galactose-and-aluminum-induced-rat-model-with-cognitive-impairments
#20
Qian Xiao, Weihua Yu, Qi Tian, Xue Fu, Xia Wang, Min Gu, Yang Lü
Chitinase activity is increased in Alzheimer's disease (AD). However, the role of chitinase1 in AD is unknown. We investigated the effects of chitinase1 on Alzheimer's pathology and microglia function. Artificial chitinase1 and chitinase inhibitor (chitinase-IN-2) were used to determine the effects of chitinase1 on inflammatory factors and β-amyloid (Aβ) oligomers deposition in D-galactose/AlCl3-induced rat model with cognitive impairments. Aβ-treated N9 microglia cells were analyzed to further verify whether the changes in inflammatory factors following chitinase1 treatment were associated with microglia alternative activation...
May 10, 2017: Neuroscience
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