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Neuroinflammation

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https://www.readbyqxmd.com/read/28728000/tailor-made-purified-human-platelet-lysate-concentrated-in-neurotrophins-for-treatment-of-parkinson-s-disease
#1
Ming-Li Chou, Joe-Wei Wu, Flore Gouel, Aurélie Jonneaux, Kelly Tillerman, Ting-Yi Renn, Charlotte Laloux, Hung-Ming Chang, Liang-Tzung Lin, Jean-Christophe Devedjian, David Devos, Thierry Burnouf
Human platelet lysates (PLs), which contain multiple neurotrophins, have been proposed for treating neurodegenerative disorders, including Parkinson's disease (PD). However, current PLs suspended in plasma have high protein content and contain fibrinogen/fibrin and, following activation, also proteolytic and thrombogenic enzymes. Upon brain administration, such PLs may saturate the cerebrospinal fluid and exert neurotoxicity. We assessed whether purified PLs, concentrated in neurotrophins, protected dopaminergic neurons in PD models...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28725183/bile-acid-mediated-sphingosine-1-phosphate-receptor-2-signaling-promotes-neuroinflammation-during-hepatic-encephalopathy-in-mice
#2
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Shamyal Khan, Juan Diocares, Anca Petrescu, Amy Wyatt, Jessica Kain, Brandi Jefferson, Sharon DeMorrow
Hepatic encephalopathy (HE) is a neuropsychiatric complication that occurs due to deteriorating hepatic function and this syndrome influences patient quality of life, clinical management strategies and survival. During acute liver failure, circulating bile acids increase due to a disruption of the enterohepatic circulation. We previously identified that bile acid-mediated signaling occurs in the brain during HE and contributes to cognitive impairment. However, the influences of bile acids and their downstream signaling pathways on HE-induced neuroinflammation have not been assessed...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28724796/host-interleukin-6-production-regulates-inflammation-but-not-tryptophan-metabolism-in-the-brain-during-murine-gvhd
#3
Ludovic Belle, Vivian Zhou, Kara L Stuhr, Margaret Beatka, Emily M Siebers, Jennifer M Knight, Michael W Lawlor, Casey Weaver, Misato Hashizume, Cecilia J Hillard, William R Drobyski
Graft-versus-host disease (GVHD) induces pathological damage in peripheral target organs leading to well-characterized, organ-specific clinical manifestations. Patients with GVHD, however, can also have behavioral alterations that affect overall cognitive function, but the extent to which GVHD alters inflammatory and biochemical pathways in the brain remain poorly understood. In the current study, we employed complementary murine GVHD models to demonstrate that alloreactive donor T cells accumulate in the brain and affect a proinflammatory cytokine milieu that is associated with specific behavioral abnormalities...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724546/high-protein-diet-promotes-sensitivity-to-cholecystokinin-and-shifts-the-cecal-microbiome-without-altering-brain-inflammation-in-diet-induced-obesity-in-rats
#4
Lixin Wang, Jonathan P Jacobs, Venu Lagishetty, Pu-Qing Yuan, Shuping Vincent Wu, Mulugeta Million, Joseph R Reeve, Joseph R Pisegna, Yvette Taché
High protein diet (HPD) curtails obesity and/or fat mass but it is unknown whether it reverses neuroinflammation, altered glucose levels, cholecystokinin (CCK) sensitivity and gut microbiome in rats fed a Western diet (WD)-induced obesity (DIO). Male rats fed a WD (high fat and sugar) for 12 weeks were switched to a HPD for 6 weeks. Body composition, food intake, meal pattern, sensitivity to intraperitoneal CCK-8S, blood glucose, brain signaling, and cecal microbiota were assessed. Compared to normal diet, WD increased body weight (9...
July 19, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28724382/activation-of-cannabinoid-receptor-type-2-attenuates-surgery-induced-cognitive-impairment-in-mice-through-anti-inflammatory-activity
#5
Lingling Sun, Rui Dong, Xin Xu, Xi Yang, Mian Peng
BACKGROUND: Neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD). Accumulated evidence indicates that cannabinoid receptor type 2 (CB2R) can mediate anti-inflammatory and immunomodulatory effects in part by controlling microglial activity. However, the impact of CB2R on postoperative cognition has not been investigated. We hypothesized that CB2R is involved in surgery-induced cognitive impairment in adult mice. METHODS: Adult C57BL/6 mice were subjected to intramedullary fixation surgery for tibial fracture under isoflurane anesthesia and CB2R agonist (JWH133) or CB2R antagonist (AM630) treatment...
July 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28723598/effects-of-tumor-necrosis-factor-blocker-on-salicylate-induced-tinnitus-in-mice
#6
Juen-Haur Hwang, David Chang-Wei Huang, Yin-Chang Lu, Wei-Shiung Yang, Tien-Chen Liu
OBJECTIVE: Neuroinflammation is considered a novel mechanism for acute tinnitus. Here, we investigated the effects of a tumor necrosis factor (TNF) blocker on the gene expression of inflammatory-cytokine in the cochlea in a tinnitus animal model. METHODS: Enbrel® (30 mg/kg, intraperitoneally (i.p.)) were administrated to the mice with the salicylate induced tinnitus for 3 days. Tinnitus score and mRNA expression levels of TNFR1, TNFR2, and N-methyl-d-aspartate receptor subunit 2B (NR2B) and its downstream regulatory element antagonist modulator (DREAM) in the cochlea of mice were measured and compared to the control...
June 1, 2017: International Tinnitus Journal
https://www.readbyqxmd.com/read/28720484/long-term-enzyme-replacement-therapy-improves-neurocognitive-functioning-and-hippocampal-synaptic-plasticity-in-immune-tolerant-alpha-mannosidosis-mice
#7
Stijn Stroobants, Markus Damme, Ann Van der Jeugd, Ben Vermaercke, Claes Andersson, Jens Fogh, Paul Saftig, Judith Blanz, Rudi D'Hooge
Alpha-mannosidosis is a glycoproteinosis caused by deficiency of lysosomal acid alpha-mannosidase (LAMAN), which markedly affects neurons of the central nervous system (CNS), and causes pathognomonic intellectual dysfunction in the clinical condition. Cognitive improvement consequently remains a major therapeutic objective in research on this devastating genetic error. Immune-tolerant LAMAN knockout mice were developed to evaluate the effects of enzyme replacement therapy (ERT) by prolonged administration of recombinant human enzyme...
July 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28720379/inhibition-of-12-15-lox-ameliorates-cognitive-and-cholinergic-dysfunction-in-mouse-model-of-hypobaric-hypoxia-via-attenuation-of-oxidative-nitrosative-stress
#8
Richa Choudhary, Udayabanu Malairaman, Anju Katyal
12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia induced memory impairment and cholinergic deficits. Male Balb/c mice subjected to simulated hypobaric hypoxia/reoxygenation condition for 3 days showed marked working memory impairment concomitant with hippocampal neuronal damage and malondialdehyde production which were significantly attenuated by baicalein, a specific inhibitor of 12/15LOX...
July 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28720149/heparanase-promotes-neuroinflammatory-response-during-subarachnoid-hemorrhage-in-rats
#9
Benjarat Changyaleket, Zhao Zhong Chong, Randal O Dull, Danop Nanegrungsunk, Haoliang Xu
BACKGROUND: Heparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between heparanase expression and neuroinflammation during subarachnoid hemorrhage. METHODS: Rats were subjected to SAH by endovascular perforation, and the expression of heparanase was determined by Western blot analysis and immunofluorescence in the ipsilateral brain cortex at 24 h post-SAH...
July 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28720101/drug-candidates-in-clinical-trials-for-alzheimer-s-disease
#10
REVIEW
Shih-Ya Hung, Wen-Mei Fu
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation...
July 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28719855/high-fat-diet-and-aging-interact-to-produce-neuroinflammation-and-impair-hippocampal-and-amygdalar-dependent-memory
#11
Sarah J Spencer, Heather D'Angelo, Alita Soch, Linda R Watkins, Steven F Maier, Ruth M Barrientos
More Americans are consuming diets higher in saturated fats and refined sugars than ever before, and based on increasing obesity rates, this is a growing trend among older adults as well. While high saturated fat diet (HFD) consumption has been shown to sensitize the inflammatory response to a subsequent immune challenge in young adult rats, the inflammatory effect of HFD in the already-vulnerable aging brain has not yet been assessed. Here, we explored whether short-term (3 days) consumption of HFD would serve as a neuroinflammatory trigger in aging animals, leading to cognitive deficits...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28719178/the-therapeutic-role-and-drug-delivery-potential-of-neuroinflammation-as-a-target-in-neurodegenerative-disorders
#12
Abhijeet Singh, Ankit Chokriwal, Madan Mohan Sharma, Devendra Jain, Juhi Saxena, Bjorn John Stephen
Neuroinflammation, the condition associated with the hyper activity of immune cells within the CNS (central nervous system) has recently been linked to a host range of neurodegenerative disorders. Targeting neuroinflammation could be of prime importance as recent research highlights the beneficial aspects associated with modulating the inflammatory mediators associated with the CNS. One of the main obstructions in neuroinflammatory treatments is the hindrance posed by the Blood Brain Barrier for the delivery of drugs...
July 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28716963/chemokine-ccl2-ccr2-signaling-induces-neuronal-cell-death-via-stat3-activation-and-il-1%C3%AE-production-after-status-epilepticus
#13
Dai-Shi Tian, Jiyun Peng, Madhuvika Murugan, Lijie Feng, Jun-Li Liu, Ukpong B Eyo, Li-Jun Zhou, Rochelle Mogilevsky, Wei Wang, Long-Jun Wu
Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1(GFP/+):CCR2(RFP/+) double transgenic mice, we demonstrated that CCL2-CCR2 signaling participated in resident microglial activation and blood-derived monocyte infiltration...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28716552/is-heterotopic-ossification-getting-nervous-the-role-of-the-peripheral-nervous-system-in-heterotopic-ossification
#14
Eleanor L Davis, Alan R Davis, Zbigniew Gugala, Elizabeth A Olmsted-Davis
Heterotopic ossification (HO), or de novo bone formation in soft tissue, is often observed following traumatic injury. Recent studies suggest that peripheral nerves may play a key functional role in this process. The results supporting a neurological basis for HO are examined in this article. Evidence supports the fact that BMPs released from bone matrix possess the capacity to induce HO. However, the process cannot be recapitulated using recombinant proteins without extremely high doses suggesting other components are required for this process...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#15
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28715117/differential-activation-of-neuronal-and-glial-stat3-in-the-spinal-cord-of-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#16
Tomohiro Ohgomori, Ryo Yamasaki, Hideyuki Takeuchi, Kenji Kadomatsu, Jun-Ichi Kira, Shozo Jinno
Signal transducer and activator of transcription (STAT) proteins are activated by phosphorylation in the spinal cord of patients suffering from amyotrophic lateral sclerosis (ALS). The major scope of our study is a comprehensive histological characterization of the mechanisms underlying neuronal and glial STAT3 activation in the pathogenesis of ALS using SOD1(G93A) mice. We calculated the fold changes (FCs, ratios vs. appropriate controls) of the numerical densities of the following phosphorylated STAT3-positive (pSTAT3)(+) cells: choline acetyltransferase (ChAT)(+) α-motoneurons, ionized calcium-binding adapter molecule 1 (Iba1)(+) microglia, and S100β(+) astrocytes in SOD1(G93A) mice...
July 17, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28714865/microglia-in-prion-diseases
#17
Adriano Aguzzi, Caihong Zhu
Prion diseases are a group of progressive and fatal neurodegenerative disorders characterized by deposition of scrapie prion protein (PrPSc) in the CNS. This deposition is accompanied by neuronal loss, spongiform change, astrogliosis, and conspicuous microglial activation. Here, we argue that microglia play an overall neuroprotective role in prion pathogenesis. Several microglia-related molecules, such as Toll-like receptors (TLRs), the complement system, cytokines, chemokines, inflammatory regulators, and phagocytosis mediators, are involved in prion pathogenesis...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28714753/pediatric-acute-onset-neuropsychiatric-syndrome-response-to-oral-corticosteroid-bursts-an-observational-study-of-patients-in-an-academic-community-based-pans-clinic
#18
Kayla Brown, Cristan Farmer, Bahare Farhadian, Joseph Hernandez, Margo Thienemann, Jennifer Frankovich
BACKGROUND: Sudden-onset severe obsessive-compulsive symptoms and/or severely restrictive food intake with at least two coinciding, similarly debilitating neuropsychiatric symptoms define Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). When associated with Group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). An abnormal immune response to infection and subsequent neuroinflammation is postulated to play an etiologic role...
July 17, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28714415/aquaporin-4-in-astrocytes-is-a-target-for-therapy-in-alzheimer-s-disease
#19
Yu-Long Lan, Jian-Jiao Chen, Gang Hu, Jun Xu, Ming Xiao, Shao Li
Current experimental evidence points to the conclusion that aquaporin 4 (AQP4), which is an important water-channel membrane protein found in the brain, could play major roles in various brain conditions pathologically including pathogenesis of Alzheimer's disease (AD). In this paper, we review how AQP4 and altered astrocyte functions interact in AD, and provide experimental evidence highlighting the importance of this topic for the future investigations. The interactions of AQP4 are as follows: (i) AQP4 could influence astrocytic calcium signaling and potassium homeostasis...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28713239/increased-white-matter-inflammation-in-aging-and-alzheimer-s-disease-brain
#20
Divya Raj, Zhuoran Yin, Marjolein Breur, Janine Doorduin, Inge R Holtman, Marta Olah, Ietje J Mantingh-Otter, Debby Van Dam, Peter P De Deyn, Wilfred den Dunnen, Bart J L Eggen, Sandra Amor, Erik Boddeke
Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis...
2017: Frontiers in Molecular Neuroscience
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