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Neuroinflammation

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https://www.readbyqxmd.com/read/29040522/behavioral-and-transcriptomic-analysis-of-trem2-null-mice-not-all-knockout-mice-are-created-equal
#1
Silvia S Kang, Aishe Kurti, Kelsey E Baker, Chia-Chen Liu, Marco Colonna, Jason D Ulrich, David M Holtzman, Guojun Bu, John D Fryer
It is clear that innate immune system status is altered in numerous neurodegenerative diseases. Human genetic studies have demonstrated that Triggering Receptor Expressed in Myeloid cells 2 (TREM2) coding variants have a strong association with Alzheimer's disease (AD) and other neurodegenerative diseases. To more thoroughly understand the impact of TREM2 in vivo, we studied the behavioral and cognitive functions of wild-type (WT) and Trem2-/- (KO) mice during basal conditions and brain function in the context of innate immune stimulation with peripherally administered lipopolysaccharide (LPS)...
October 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040306/micheliolide-suppresses-lps-induced-neuroinflammatory-responses
#2
Zhaomeng Sun, Guodong Li, Tanjun Tong, Jun Chen
Microglia-involved neuroinflammation is thought to promote brain damage in various neurodegenerative disorders. Thus, inhibition of microglial over-activation may have a therapeutic benefit for the treatment of neurodegenerative disorders. Micheliolide (MCL) is a sesquiterpene lactone which inhibits various inflammatory response. However, whether MCL can inhibit neuroinflammation caused by LPS-activated BV2 microglia has not yet been explored. In this study, we demonstrated that treatment of BV2 cells with MCL significantly repressed LPS-stimulated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, as well as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) induction...
2017: PloS One
https://www.readbyqxmd.com/read/29036814/curcumin-ameliorates-neuroinflammation-neurodegeneration-and-memory-deficits-in-p25-transgenic-mouse-model-that-bears-hallmarks-of-alzheimer-s-disease
#3
Jeyapriya Raja Sundaram, Charlene Priscilla Poore, Noor Hazim Bin Sulaimee, Tej Pareek, Wei Fun Cheong, Markus R Wenk, Harish C Pant, Sally A Frautschy, Chian-Ming Low, Sashi Kesavapany
Several studies have indicated that neuroinflammation is indeed associated with neurodegenerative disease pathology. However, failures of recent clinical trials of anti-inflammatory agents in neurodegenerative disorders have emphasized the need to better understand the complexity of the neuroinflammatory process in order to unravel its link with neurodegeneration. Deregulation of Cyclin-dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's disease (AD)...
October 12, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29035306/platelet-endothelial-cell-adhesion-molecule-1-and-oligodendrogenesis-significance-in-alcohol-use-disorders
#4
REVIEW
Chitra D Mandyam, Emmanuel G Villalpando, Noah L Steiner, Leon W Quach, McKenzie J Fannon, Sucharita S Somkuwar
Alcoholism is a chronic relapsing disorder with few therapeutic strategies that address the core pathophysiology. Brain tissue loss and oxidative damage are key components of alcoholism, such that reversal of these phenomena may help break the addictive cycle in alcohol use disorder (AUD). The current review focuses on platelet endothelial cell adhesion molecule 1 (PECAM-1), a key modulator of the cerebral endothelial integrity and neuroinflammation, and a targetable transmembrane protein whose interaction within AUD has not been well explored...
October 16, 2017: Brain Sciences
https://www.readbyqxmd.com/read/29034508/ulk4-deficiency-leads-to-hypomyelination-in-mice
#5
Min Liu, Ping Xu, Zhenlong Guan, Xiaohong Qian, Peter Dockery, Una Fitzgerald, Timothy O'Brien, Sanbing Shen
Brain nerve fibers are insulated by myelin which is produced by oligodendrocytes. Defects in myelination are increasingly recognized as a common pathology underlying neuropsychiatric and neurodevelopmental disorders, which are associated with deletions of the Unc-51-like kinase 4 (ULK4) gene. Key transcription factors have been identified for oligodendrogenesis, but little is known about their associated regulators. Here we report that Ulk4 acts as a key regulator of myelination. Myelination is reduced by half in the Ulk4(tm1a/tm1a) hypomorph brain, whereas expression of axonal marker genes Tubb3, Nefh, Nefl and Nefm remains unaltered...
October 16, 2017: Glia
https://www.readbyqxmd.com/read/29034441/the-oral-pretreatment-of-glycyrrhizin-prevents-surgery-induced-cognitive-impairment-in-aged-mice-by-reducing-neuroinflammation-and-alzheimer-s-related-pathology-via-hmgb1-inhibition
#6
Zhong-Hong Kong, Xin Chen, Hui-Po Hua, Liang Liang, Long-Juan Liu
Neuroinflammation and Alzheimer's-related pathology play essential roles in postoperative cognitive dysfunction (POCD). High-mobility group box 1 (HMGB1) is well known as a pivotal mediator in neuroinflammation, and its associations with Alzheimer's-related pathology and POCD have been also revealed. Glycyrrhizin is a nature inhibitor of HMGB1 and is reported with neuroprotective effects through oral administration. Therefore, the present study aims to test the hypothesis that the oral pretreatment of glycyrrhizin prevents POCD by inhibiting HMGB1-induced neuroinflammation and Alzheimer's-related pathology in aged mice...
October 16, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29033949/microarray-analysis-identifies-the-potential-role-of-long-non-coding-rna-in-regulating-neuroinflammation-during-japanese-encephalitis-virus-infection
#7
Yunchuan Li, Hao Zhang, Bibo Zhu, Usama Ashraf, Zheng Chen, Qiuping Xu, Dengyuan Zhou, Bohan Zheng, Yunfeng Song, Huanchun Chen, Jing Ye, Shengbo Cao
Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. JEV-induced neuroinflammation is characterized by profound neuronal cells damage accompanied by activation of glial cells. Albeit long non-coding RNAs (lncRNAs) have been emerged as important regulatory RNAs with profound effects on various biological processes, it is unknown how lncRNAs regulate JEV-induced inflammation. Here, using microarray approach, we identified 618 lncRNAs and 1,007 mRNAs differentially expressed in JEV-infected mice brain...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29032033/effect-of-mofezolac-galactose-distance-in-conjugates-targeting-cyclooxygenase-cox-1-and-cns-glut-1-carrier
#8
Maria Grazia Perrone, Paola Vitale, Savina Ferorelli, Angelina Boccarelli, Mauro Coluccia, Alessandra Pannunzio, Federica Campanella, Giuseppe Di Mauro, Carmela Bonaccorso, Cosimo G Fortuna, Antonio Scilimati
Neuroinflammation is the earliest stage of several neurological and neurodegenerative diseases. In the case of neurodegenerative disorders, it takes place about 15-20 years before the appearance of specific neurodegenerative clinical symptoms. Constitutive microglial COX-1 is one of the pro-inflammatory players of the neuroinflammation. Novel compounds 3, 14 and 15 (Galmof0, Galmof5 and Galmof11, respectively) were projected, and their synthetic methodologies developed, by linking by an ester bond, directly or through a C5 or C11 unit linker the highly selective COX-1 inhibitor mofezolac (COXs selectivity index > 6000) to galactose in order to obtain substances capable to cross blood-brain barrier (BBB) and control the CNS inflammatory response...
September 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031614/high-mobility-group-box-1-is-a-novel-pathogenic-factor-and-a-mechanistic-biomarker-for-epilepsy
#9
Teresa Ravizza, Gaetano Terrone, Alessia Salamone, Federica Frigerio, Silvia Balosso, Daniel J Antoine, Annamaria Vezzani
Approximately 30% of epilepsy patients experience seizures that are not controlled by the available drugs. Moreover, these drugs provide mainly a symptomatic treatment since they do not interfere with the disease's mechanisms. A mechanistic approach to the discovery of key pathogenic brain modifications causing seizure onset, recurrence and progression is instrumental for designing novel and rationale therapeutic interventions that could modify the disease course or prevent its development. In this regard, increasing evidence shows that neuroinflammation is a pathogenic factor in drug-resistant epilepsies...
October 12, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29031551/neuroinflammation-and-neurosteroidogenesis-reciprocal-modulation-during-injury-to-the-adult-zebra-finch-brain
#10
Alyssa L Pedersen, Jenna L Brownrout, Colin J Saldanha
Estrogens like estradiol (E2) via its receptors are pluripotent steroid hormones that exert a profound influence on the developing and adult brain in many vertebrates. In songbirds and mammals, acute brain injury resulting from mechanical damage, anoxia and ischemia rapidly upregulates aromatase and E2 synthesis. Interestingly, this E2 provision occurs due to the induction of aromatase expression in reactive astrocytes in areas surrounding brain injury. The resultant increase in E2 is neuroprotective with established influences on apoptosis, gliosis, cytogenesis, neurogenesis and neuroinflammation...
October 12, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/29029824/increased-cerebrospinal-fluid-levels-of-cytokines-monocyte-chemoattractant-protein-1-mcp-1-and-macrophage-inflammatory-protein-1%C3%AE-mip-1%C3%AE-in-patients-with-amyotrophic-lateral-sclerosis
#11
H R Martínez, C E Escamilla-Ocañas, C R Camara-Lemarroy, M T González-Garza, J Moreno-Cuevas, M A García Sarreón
INTRODUCTION: Neuroinflammation has recently been described in amyotrophic lateral sclerosis (ALS). However, the precise role of such proinflammatory cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in ALS has not yet been determined. In this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1β levels and assessed their association with the duration and severity of ALS. METHODS: Concentrations of MCP-1 and MIP-1β were determined in the CSF of 77 patients diagnosed with ALS and 13 controls...
October 10, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29028353/activated-microglia-targeting-dendrimer-minocycline-conjugate-as-therapeutics-for-neuroinflammation
#12
Rishi Sharma, Soo-Young Kim, Anjali Sharma, Zhi Zhang, Siva Pramodh Kambhampati, Sujatha Kannan, Rangaramanujam M Kannan
Brain related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood brain barrier (BBB), and potency. Despite its potential in the clinic, and in preclinical models, the high doses needed to affect a positive therapeutic response has led to side effects...
October 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29027011/let-s-make-microglia-great-again-in-neurodegenerative-disorders
#13
REVIEW
Marie-Victoire Guillot-Sestier, Terrence Town
All of the common neurodegenerative disorders-Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion diseases-are characterized by accumulation of misfolded proteins that trigger activation of microglia; brain-resident mononuclear phagocytes. This chronic form of neuroinflammation is earmarked by increased release of myriad cytokines and chemokines in patient brains and biofluids. Microglial phagocytosis is compromised early in the disease process, obfuscating clearance of abnormal proteins...
October 12, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29026534/recent-advances-in-hepatic-encephalopathy
#14
REVIEW
Victoria Liere, Gurkarminder Sandhu, Sharon DeMorrow
Hepatic encephalopathy describes the array of neurological alterations that occur during acute liver failure or chronic liver injury. While key players in the pathogenesis of hepatic encephalopathy, such as increases in brain ammonia, alterations in neurosteroid levels, and neuroinflammation, have been identified, there is still a paucity in our knowledge of the precise pathogenic mechanism. This review gives a brief overview of our understanding of the pathogenesis of hepatic encephalopathy and then summarizes the significant recent advances made in clinical and basic research contributing to our understanding, diagnosis, and possible treatment of hepatic encephalopathy...
2017: F1000Research
https://www.readbyqxmd.com/read/29025435/withania-somnifera-as-a-potential-candidate-to-ameliorate-high%C3%A2-fat-diet-induced-anxiety-and-neuroinflammation
#15
Taranjeet Kaur, Gurcharan Kaur
BACKGROUND: The epidemic of obesity has reached alarming levels in both developing and developed nations. Excessive calorie intake and sedentary lifestyle due to technological advancements are the main causal factors for overweight and obesity among the human population. Obesity has been associated with a number of co-morbidities such as hypertension, type 2 diabetes mellitus, cardiovascular diseases, and neurodegeneration and dementia. The progression of neurological disorders in obese subjects has been mainly attributed to neuroinflammation...
October 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29025157/chronic-pain-after-traumatic-brain-injury-pathophysiology-and-pain-mechanisms
#16
Karen-Amanda Irvine, J David Clark
Background: Traumatic brain injury refers to a broad range of neurological, cognitive, and emotional factors that result from the application of an external force to the head. Individuals recovering from traumatic brain injury will frequently experience acute and chronic pain. Objective: The objective of this paper is to discuss the pathophysiological changes resulting from traumatic brain injury and how these may be involved in the development and persistence of pain after injury...
August 29, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29024008/immunization-with-%C3%AE-synuclein-grp94-reshapes-peripheral-immunity-and-suppresses-microgliosis-in-a-chronic-parkinsonism-model
#17
Javier Villadiego, Adahir Labrador-Garrido, Jaime M Franco, Magdalena Leal-Lasarte, Erwin J De Genst, Christopher M Dobson, David Pozo, Juan J Toledo-Aral, Cintia Roodveldt
Neuroinflammation mediated by chronically activated microglia, largely caused by abnormal accumulation of misfolded α-synuclein (αSyn) protein, is known to contribute to the pathophysiology of Parkinson's disease (PD). In this work, based on the immunomodulatory activities displayed by particular heat-shock proteins (HSPs), we tested a novel vaccination strategy that used a combination of αSyn and Grp94 (HSPC4 or Gp96) chaperone and a murine PD model. We used two different procedures, first, the adoptive transfer of splenocytes from αSyn/Grp94-immunized mice to recipient animals, and second, direct immunization with αSyn/Grp94, to study the effects in a chronic mouse MPTP-model of parkinsonism...
October 11, 2017: Glia
https://www.readbyqxmd.com/read/29021779/xenon-reduces-neuronal-hippocampal-damage-and-alters-the-pattern-of-microglial-activation-after-experimental-subarachnoid-hemorrhage-a-randomized-controlled-animal-trial
#18
Michael Veldeman, Mark Coburn, Rolf Rossaint, Hans Clusmann, Kay Nolte, Benedikt Kremer, Anke Höllig
OBJECTIVE: The neuroprotective properties of the noble gas xenon have already been demonstrated using a variety of injury models. Here, we examine for the first time xenon's possible effect in attenuating early brain injury (EBI) and its influence on posthemorrhagic microglial neuroinflammation in an in vivo rat model of subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats (n = 22) were randomly assigned to receive either Sham surgery (n = 9; divided into two groups) or SAH induction via endovascular perforation (n = 13, divided into two groups)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29019394/studies-on-16-17-pyrazoline-substituted-heterosteroids-as-anti-alzheimer-and-anti-parkinsonian-agents-using-lps-induced-neuroinflammation-models-of-mice-and-rats
#19
Ranjit Singh, Sridhar Thota, Ranju Bansal
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common forms of neurodegenerative disorders. Dehydroepiandrosterone (DHEA) has been reported as a neuroprotective steroid useful in the therapeutic management of neurodegenerative disorders such as AD and PD. Herein we report the synthesis and evaluation of a new series of 16,17-pyrazolinyl DHEA analogues 2-4a-d as neuroprotective agents using LPS-induced neuroinflammation animal models. Treatment with the pyrazoline substituted steroids considerably improved the LPS-induced learning, memory and movement deficits in animal models...
October 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29017971/induction-of-suppressor-of-cytokine-signaling-3-via-hsf-1-hsp70-tlr4-axis-attenuates-neuroinflammation-and-ameliorates-postoperative-pain
#20
Yi-Xin Fan, Cheng Qian, Bingqian Liu, Chaoyu Wang, Haijiao Liu, Xiuxiu Pan, Peng Teng, Liang Hu, Guangqin Zhang, Yuan Han, Mi Yang, Xue-Feng Wu, Wen-Tao Liu
Postoperative pain is a common form of acute pain that, if not managed effectively, can become chronic pain. Evidence has shown that glia, especially microglia, mediate neuroinflammation, which plays a vital role in pain sensitization. Moreover, toll-like receptor 4 (TLR4), the tumor necrosis factor receptor (TNF-R), the interleukin-1 receptor (IL-1R), and the interleukin-6 receptor (IL-6R) have been considered key components in central pain sensitization and neuroinflammation. Therefore, we hypothesized that activation of the body's endogenous "immune brakes" will inhibit these receptors and achieve inflammation tolerance as well as relieve postoperative pain...
October 7, 2017: Brain, Behavior, and Immunity
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