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Brain And Inflammation

E Martianova, V A Aniol, A O Manolova, A A Kvichansky, N V Gulyaeva
Lentiviral transduction is a powerful tool and widely used in neuroscience research to manipulate gene expression of cells. However, the injection of lentiviral vectors in the brain is not totally benign, it potentially induces focal neuroinflammation. Upon inflammation, microglial cells get activated and can induce major changes in tissue environment, which may interfere with experimental results. In the current study, two weeks after the injection of control viral construction in the dentate gyrus (DG) of rats, an activation of microglia was detected...
February 13, 2019: Acta Histochemica
Richard Voldřich, Martin Májovský, Martin Chovanec, David Netuka
BACKGROUND: Pneumocephalus is commonly associated with cranial trauma including surgical interventions. Spontaneous pneumocephalus on the other hand is a rare diagnosis. Reported cases were predominantly unilateral. We report unique case of a bilateral spontaneous pneumocephalus probably related to bilateral tegmen defect related to repeated Politzer maneuvers. CASE DESCRIPTION: A 78-year-old man suffered from vertigo, tinnitus, instability and mild expressive aphasia...
February 13, 2019: World Neurosurgery
Tiyasha Sarkar, Nisha Patro, Ishan K Patro
Early life Stress is a worldwide concern linked with development of later life neurological disorder. Early developmental age is sensitive to many prominent environmental insults like malnourishment, immune inflammation, abuse, maternal separation, alcohol and drugs. Hence, an individual during an early age encounters more than one simultaneous stressor that leads to impairment of cognitive and behavioral abilities, a symptom common to most of the neurological disorders. Stressors like malnourishment and immune inflammation are common and encountered by a huge number of populations, contributing enormously to a damaged CNS and in most of the cases they act synergistically in dependency to each other, giving rise to the concept of multi-hit...
February 13, 2019: Brain Research Bulletin
Aidan C Smith, Ryan C Holden, Sherry M Rasmussen, Michael R Hoane, Michael J Hylin
Age is a consistent predictor of outcome following traumatic brain injury (TBI). Although children and adolescents have the highest rate of hospitalizations and long-term disabilities, few preclinical studies have attempted to model and treat TBI in this population. Studies using nicotinamide (NAM), a soluble B-group vitamin, in older animals (3-6 months) have shown improved functional recovery in experimental models of TBI. The purpose of this study was two-fold: to examine the preclinical efficacy of NAM at different doses on behavioral outcomes in juvenile rats and examine the microglial response over time...
February 13, 2019: Behavioural Brain Research
Kunal Dhiman, Kaj Blennow, Henrik Zetterberg, Ralph N Martins, Veer Bala Gupta
Alzheimer's disease (AD) is a multifactorial age-related brain disease. Numerous pathological events run forth in the brain leading to AD. There is an initial long, dormant phase before the clinical symptoms become evident. There is a need to diagnose the disease at the preclinical stage since therapeutic interventions are most likely to be effective if initiated early. Undoubtedly, the core cerebrospinal fluid (CSF) biomarkers have a good diagnostic accuracy and have been used in clinical trials as end point measures...
February 15, 2019: Cellular and Molecular Life Sciences: CMLS
T Yang, G Xu, P T Newton, A S Chagin, S Mkrtchian, M Carlström, X-M Zhang, R A Harris, M Cooter, M Berger, K R Maddipati, K Akassoglou, N Terrando
BACKGROUND: Resolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects of MaR1 on postoperative neuroinflammation, macrophage activity, and cognitive function in mice. METHODS: Adult male C57BL/6 (n=111) and Ccr2RFP/+ Cx3cr1GFP/+ (n=54) mice were treated with MaR1 before undergoing anaesthesia and orthopaedic surgery...
March 2019: British Journal of Anaesthesia
Roohi Mirza, Bhupesh Sharma
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with two major behavioral symptoms i.e. repetitive behavior and social-communication impairment. The unknown etiology of ASD is responsible for the difficulty in identifying the possible therapeutic modulators for ASD. Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy. Therefore, prenatal exposure of VPA induced autism spectrum disorder like phenotypes in both human and rodents. Peroxisome proliferator-activated receptor-alpha (PPAR-α) is widely localized in the brain...
February 12, 2019: Brain Research Bulletin
Q Raas, C Gondcaille, Y Hamon, V Leoni, C Caccia, F Ménétrier, G Lizard, D Trompier, S Savary
X-linked adrenoleukodystrophy (X-ALD), the most frequent peroxisomal disorder, is associated with mutation in the ABCD1 gene which encodes a peroxisomal ATP-binding cassette transporter for very long-chain fatty acids (VLCFA). The biochemical hallmark of the disease is the accumulation of VLCFA. Peroxisomal defect in microglia being now considered a priming event in the pathology, we have therefore generated murine microglial cells mutated in the Abcd1 gene and its closest homolog, the Abcd2 gene. Using CRISPR/Cas9 gene editing strategy, we obtained 3 cell clones with a single or double deficiency...
February 12, 2019: Biochimica et biophysica acta. Molecular and cell biology of lipids
QianQian Han, QianQian Liu, Hui Zhang, Meili Lu, Hongxin Wang, Futian Tang, Yingjie Zhang
BACKGROUND Simvastatin, an HMG-CoA reductase inhibitor, has been reported to exert multiple protective effects on the cardiovascular system. However, the molecular mechanism remains to be examined. The present study was designed to study the effects of simvastatin on cardiac hypertrophy in diabetic rats and to explore its potential mechanism. MATERIAL AND METHODS Sprague-Dawley rats were assigned into a control (Con) group, a streptozotocin (STZ) group, and a STZ+simvastatin (STZ+SIM) group. The level of reactive oxygen species (ROS) was measured by using dihydroethidium (DHE) staining...
February 15, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Joanna Jaworska, Teresa Zalewska, Joanna Sypecka, Malgorzata Ziemka-Nalecz
Neonatal hypoxic-ischemic (HI) brain injury likely represents the major cause of long-term neurodevelopmental disabilities in surviving babies. Despite significant investigations, there is not yet any known reliable treatment to reduce brain damage in suffering infants. Our recent studies in an animal model of HI revealed the therapeutic potential of a histone deacetylase inhibitor (HDACi). The neuroprotective action was connected with the stimulation of neurogenesis in the dentate gyrus subgranular zone. In the current study, we investigated whether HDACi-sodium butyrate (SB)-would also lead to neurogenesis in the subventricular zone (SVZ)...
February 14, 2019: Molecular Neurobiology
Rose Mary Ferreira Lisboa Da Silva, Cláudia Madeira Miranda, Tong Liu, Gary Tse, Leonardo Roever
Atrial fibrillation (AF) is one of the cardiovascular risk factors for dementia. Several longitudinal studies have reported an association between AF and dementia independently of stroke history. Although the mechanisms underlying this association are not fully understood, proposed mechanisms include cerebral hypoperfusion, inflammation, genetic factors, cerebral microbleeds, and recurrent silent cerebral ischemia. Oral anticoagulation can be used to minimize risk of cognitive decline and dementia, given that brain insults can be caused by chronic microemboli or microbleeds...
2019: Frontiers in Neuroscience
Qing Zhu, Yong-Yi Zhu, Wei-Ning Wang
High fat diet (HFD)-induced obesity is associated with insulin resistance (IR) and other chronic, diet associated illnesses, including neuroinflammation and brain injury. However, the involvement of inflammatory response in HFD-elicited central nerve injury has yet to be fully determined. Recent studies have indicated that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS), also known as TRPC4AP, plays an essential role in regulating inflammation via the meditation of NF-κB signaling...
February 11, 2019: Biochemical and Biophysical Research Communications
Christine Silwedel, Axel Haarmann, Markus Fehrholz, Heike Claus, Christian P Speer, Kirsten Glaser
BACKGROUND: Ureaplasma species (spp.) are commonly regarded as low-virulent commensals but may cause invasive diseases in immunocompromised adults and in neonates, including neonatal meningitis. The interactions of Ureaplasma spp. with host defense mechanisms are poorly understood. This study addressed Ureaplasma-driven cell death, concentrating on apoptosis as well as inflammatory cell death. METHODS: Human brain microvascular endothelial cells (HBMEC) were exposed to Ureaplasma (U...
February 14, 2019: Journal of Neuroinflammation
Devon Watts, Bianca Pfaffenseller, Bianca Wollenhaupt-Aguiar, Luiza Paul Géa, Taiane de Azevedo Cardoso, Flavio Kapczinski
Present antidepressant treatments are only helpful in a quarter of patients with bipolar depression, and new strategies are warranted. Increasing evidence suggests that accelerated polyamine metabolism is associated with the pathophysiology of depression. Polyamines regulate stress responses, inflammation, and neuronal signaling in the central and enteric nervous system. Agmatine is a promising target of altered polyamine metabolism considering its unique ability to regulate intracellular polyamine content and neuroprotective effects...
February 15, 2019: Expert Opinion on Therapeutic Targets
J Key, A K Mueller, S Gispert, L Matschke, I Wittig, O Corti, C Münch, N Decher, G Auburger
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder in the old population. Among its monogenic variants, a frequent cause is a mutation in the Parkin gene (Prkn). Deficient function of Parkin triggers ubiquitous mitochondrial dysfunction and inflammation in the brain, but it remains unclear how selective neural circuits become vulnerable and finally undergo atrophy. We attempted to go beyond previous work mostly done in peripheral tumor cells, which identified protein targets of Parkin activity, an ubiquitin E3 ligase...
February 11, 2019: Neurobiology of Disease
Jianxiong Jiang, Ying Yu, Erika Kinjo, Yifeng Du, Hoang Nguyen, Ray Dingledine
Glutamate receptor-mediated excitotoxicity is a common pathogenic process in many neurological conditions including epilepsy. Prolonged seizures induce elevations in extracellular glutamate that contribute to excitotoxic damage, which in turn can trigger chronic neuroinflammatory reactions, leading to secondary damage to the brain. Blocking key inflammatory pathways could prevent such secondary brain injury following the initial excitotoxic insults. Prostaglandin E2 (PGE2 ) has emerged as an important mediator of neuroinflammation-associated injury, in large part via activating its EP2 receptor subtype...
February 11, 2019: Neuropharmacology
Mengmeng Li, Dongmei Zhang, Xin Ge, Xiangyang Zhu, Yong Zhou, Yi Zhang, Xiao Peng, Aiguo Shen
Activating transcription factor 2 (ATF2), a member of the alkaline-leucine zipper family, is widely expressed in various tissues, and reportedly involved in inflammatory responses to various irritates, but its role in the central nervous system (CNS) remains unclear. This study aimed to investigate the expression and biological function of ATF2 in CNS inflammation. Utilizing the LPS-induced neuroinflammation model on mice, we first found ATF2 up-regulation and its co-localization with microglia in inflamed mice brain...
February 11, 2019: Experimental Cell Research
Marc Parisien, Alexander Samoshkin, Shannon N Tansley, Marjo H Piltonen, Loren J Martin, Nehme El-Hachem, Concetta Dagostino, Massimo Allegri, Jeffrey S Mogil, Arkady Khoutorsky, Luda Diatchenko
Chronic pain is a debilitating and poorly treated condition whose underlying mechanisms are poorly understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with pain processing, supporting molecular and cellular mechanisms that maintain painful states. However, it is not known whether transcriptome changes can be used to reconstruct a molecular pathophysiology of pain. In the current study, we identify molecular pathways contributing to chronic pain states through the analysis of global changes in the transcriptome of dorsal root ganglia, spinal cord, brain, and blood in mouse assays of nerve injury- and inflammation-induced pain...
January 3, 2019: Pain
Vitka Gres, Julia Kolter, Daniel Erny, Philipp Henneke
In the healthy brain, microglia and other CNS macrophages are the most abundant immune cell type. Thus, they form the natural immune cell interface with streptococci, which are the leading cause of bacterial meningitis and encephalitis in infants and young children. In homeostasis, the blood-brain barrier allows for very limited access of immune cells circulating in the periphery. During bacterial meningoencephalitis, however, origin and fate of CNS macrophages are massively altered. This review summarizes the emerging knowledge on the sequence of reciprocal events between streptococci and CNS macrophages leading to host resistance, acute inflammation, changes in resident innate immune cells of the brain, and long-term neuronal damage...
February 14, 2019: Journal of Leukocyte Biology
Calum D Moulton, Polychronis Pavlidis, Christine Norton, Sam Norton, Carmine Pariante, Bu Hayee, Nick Powell
Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), whilst sleep difficulties and fatigue are even more common. Comorbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators...
February 14, 2019: Clinical and Experimental Immunology
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