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Search Results: 1 - 10 of 166 matches for " neuroinflammation "
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Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy
Paul J Orchard, Troy Lund, Wes Miller, Steven M Rothman, Gerald Raymond, David Nascene, Lisa Basso, James Cloyd, Jakub Tolar
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-144
Abstract: As cellular infiltration has been observed in C-ALD, including activation of monocytes and macrophages, we evaluated the activity of chitotriosidase in the plasma and spinal fluid of boys with active C-ALD. Due to genotypic variations in the chitotriosidase gene, these were also evaluated.We document elevations in chitotriosidase activity in the plasma of patients with C-ALD (n = 38; median activity 1,576 ng/mL/hr) vs. controls (n = 16, median 765 ng/mL/hr, p = 0.0004), and in the CSF of C-ALD patients (n = 38; median activity 4,330 ng/mL/hr) vs. controls (n = 16, median 0 ng/mL/hr, p < 0.0001). In addition, activity levels of plasma and CSF chitotriosidase prior to transplant correlated with progression as determined by the Moser/Raymond functional score 1 year following transplantation (p = 0.002 and < 0.0001, respectively).These findings confirm elevation of chitotriosidase activity in patients with active C-ALD, and suggest that these levels predict prognosis of patients with C-ALD undergoing transplantation.Adrenoleukodystrophy (ALD) is an X-linked, peroxisomal disorder of very long chain fatty acid (VLCFA) metabolism, resulting in the accumulation of VLCFA in the adrenal gland, testes and brain. The disease frequency is approximately 1 in 17,000 males, and has been reported to be similar in distribution across ethnic and racial groups [1,2]. The capacity to metabolize VLCFA, a reaction that normally takes place in the peroxisome, is impaired in patients with X-ALD due to defects in the ABCD1 gene encoding a peroxisomal membrane protein designated ALDp. A large number of genetic mutations have been identified as causing disease, and there is substantial clinical variability within kindreds despite a conserved genotype [2,3].The most severe phenotype of ALD is the cerebral form (C-ALD), which is observed in approximately 40% of children affected by ALD. The median age of clinical onset is 7 years. A characteristic finding associated with C-ALD is inflammation of
Aspectos inmunológicos en la enfermedad de Parkinson
González-Torres, Laura Clementina;Armendáriz-Borunda, Juan;
Archivos de neurociencias (México, D.F.) , 2005,
Abstract: parkinson disease is a neurodegenerative disorder that affects 50/100,000 individuals in mexico. parkinson disease is characterized by reduction in dopamine content of the substancia nigra pars compacta resulting in 1055 of domamine-containing neurons. the postulated cause of the disease includes several processes: 1. a growth factor deficiency, such as nerve growth factor and brain-derived neurotrophic factor, cytokines which can prevent and protect neuronal cell death; which may regulate glial phenotype, t lymphocytes and blymphocytes functions, and the surviving pathway signals; 2. dysfunction of the ubiquitin-proteasome system related to the histophatology of this disease; and 3. excitotoxic mechanisms, resulting in information of free radicals and the neuroinflammatory processes leading to autoimmunity or a failing immune response.
The TARC/sICAM5 Ratio in Patient Plasma is a Candidate Biomarker for Drug Resistant Epilepsy
John R. Pollard,Clifton L. Dalgard,Sai K. Ivaturi,Harvey B. Pollard
Frontiers in Neurology , 2013, DOI: 10.3389/fneur.2012.00181
Abstract: Epilepsy is a common affliction that involves inflammatory processes. There are currently no definitive chemical diagnostic biomarkers in the blood, so diagnosis is based on a sometimes expensive synthesis of clinical observation, radiology, neuro-psychological testing, and interictal and ictal EEG studies. Soluble ICAM5 (sICAM5), also known as telencephalin, is an anti-inflammatory protein of strictly central nervous system tissue origin that is also found in blood. Here we have tested the hypothesis that plasma concentrations of select inflammatory cytokines, including sICAM5, might serve as biomarkers for epilepsy diagnosis. To test this hypothesis, we developed a highly sensitive and accurate electrochemiluminescent ELISA assay to measure sICAM5 levels, and measured levels of sICAM5 and 18 other inflammatory mediators in epilepsy patient plasma and controls. Patient samples were drawn from in-patients undergoing video-EEG monitoring, without regard to timing of seizures. Differences were defined by t-test, and Receiver Operating Condition (ROC) curves determined the ability of these tests to distinguish between the two populations. In epilepsy patient plasmas, we found that concentrations of anti-inflammatory sICAM5 are reduced (p = 0.002) and pro-inflammatory IL-1β, IL-2, and IL-8 are elevated. TARC (thymus and activation regulated chemokine, CCL17) concentrations trend high. In contrast, levels of BDNF and a variety of other pro-inflammatory mediators are not altered. Based on p-value and ROC analysis, we find that the ratio of TARC/sICAM5 discriminates accurately between patients and controls, with an ROC Area Under the Curve (AUC) of 1.0 (p = 0.034). In conclusion, we find that the ratio of TARC to sICAM5 accurately distinguishes between the two populations and provides a statistically and mechanistically compelling candidate blood biomarker for drug resistant epilepsy.
The Neuroinflammatory Response Induced by PAF Can Be Attenuated by BN52021 Administration  [PDF]
Ruizhang Han, Jinjia Hu, Guojun Su
Neuroscience & Medicine (NM) , 2011, DOI: 10.4236/nm.2011.24049
Abstract: Objective: The purpose of this study was to determine whether BN52021, a platelet-activation factor receptor (PAFR) antagonist, could provide neuroprotection from the cytotoxic effects of PAF-induced neuroinflammation. Methods: The inflammagen platelet-activation factor (PAF) was first added to cultured PC12 cells. BN52021 was then added 24 hours later, survival rate and rate of apoptosis of the PC12 cells was determined by the MTT method and flow cytometry. In addition, PAF was injected into the fourth ventricle, and the effect of BN52021 administration was determined in rats. Results: PAF induced apoptosis in cultured PC12 cells, and BN52021 administration protected PC12 cells from PAF-induced apoptosis. When PAF is injected into the fourth ventricle, PAF induces acute neuroinflammation in the whole brain of rats. Acute PAF infusions also impaired spatial recognition in rats. The peripheral administration of BN52021 (i.p.) protected the rats from this impairment in spatial recognition. Conclusion: The PAFR antagonist BN52021 provides neuroprotection from the cytotoxic effects induced by the inflamagen PAF.
The PARF Antagonist AChE Inhibitor PMS777 Attenuates LPS-Induced Acute Neuroinflammation  [PDF]
Jin-Jia Hu, Juan Li, Zhang Wei, Hong-Yu Gu, Bi-Yun Shao, Ding Wen Long, Hong-Zhuan Chen
Neuroscience & Medicine (NM) , 2011, DOI: 10.4236/nm.2011.24047
Abstract: When injected into the fourth ventricle, the proinflammagen lipopolysaccharide (LPS) induces acute neuroinflammation in the whole brain of rats. The new compound PMS777 is a novel platelet-activating factor receptor (PAFR) antagonist and acetylcholinesterase (AChE) inhibitor. The current study determined whether PMS777 could provide neuroprotection from the cytotoxic effects associated with LPS-induced neuroinflammation. Acute LPS infusions impaired recognition in rats as measured by the Morris water maze. In addition, LPS infusions decreased the number of AChE positive cells, and increased the number of OX-42 immunoreactive microglia and GFAP immunoreactive astrocytes in the hippocampus, the cortex and the basal nuclei. Furthermore, acute infusions of LPS also impaired organelles associated with protein synthesis. Peripheral administration of PMS777 (i.e., intraperitoneal injection) protected against the impairment in recognition, and attenuated the cytotoxic effects of the acute inflammatory processes upon cholinergic cells, microglia, astrocytes and ultrastructure of hippocampal cells. Here, we propose that the cytotoxic effects of acute neuroinflammation may involve the release of PAF and loss of cholinergic neurons, and this mechanism leads to neuronal dysfunction and spatial memory impairment. The PAFR antagonist inhibitor and AChE inhibitor PMS777 could provide neuroprotection from the cytotoxic effects induced by LPS.
The activity of antiparkinsonian drug hemantane in models of peripheral inflammation and lipopolysaccharide-induced neuroinflammation  [PDF]
Elena Ivanova, Inga Kapitsa, Elena Valdman, Tatyana Voronina
Advances in Parkinson's Disease (APD) , 2013, DOI: 10.4236/apd.2013.21003
Abstract: A large body of literature supports the idea that inflammation exacerbates neurodegenerative pathology. This idea is also supported by the fact that intracerebral or intraperitoneal injection of lipopolysaccharide (LPS) induces symptoms of Parkinson’s disease in rats. The aim of this study is to evaluate the anti-inflammatory effects of the novel antiparkinsonian drug hemantane (N-2(adamantyl)hexamethylenimine hydrochloride), which is currently undergoing clinical trials, in models of peripheral inflammation and neuroinflammation and to investigate its ulcerogenic action, which is a common side effect of nonselective nonsteroidal anti-inflammatory drugs. Acetic acid-induced peritonitis in mice was used as a model of peripheral inflammation. Effect on the stomach was investigated in rats were deprived of food for 16 hours and then were treated with 0.2 LD50 of hemantane or the comparator drug diclofenac sodium per os. Injection of LPS in the left substantia nigra pars compacta in rats was chosen as a model of neuroinflammation. LPS-induced body weight loss, forelimb akinesia and behavioral changes caused by irritating odor were registered in rats. Hemantane in the dosage range of 10 - 40 mg/kg demonstrates anti-inflammatory activity and significantly decreases the intensity of exudative reaction in a model of acetic acid-induced peritonitis in mice. Additionally, at the dose of 0.2 LD50 orally it did not damage the gastric mucosa of rats. In a model of neuroinflammation induced by a unilateral injection of LPS, hemantane (10 mg/kg) prevents weight loss, development of forepaw akinesia contralateral to the operation, and smell disturbance in rats. Effectiveness of hemantane in the animal models of peripheral inflammation and neuroinflammation make it possible to suggest a new application of hemantane as a safe anti-inflammatory drug.


Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation
Kai Fan, Xuefei Wu, Bin Fan, Ning Li, Yongzhong Lin, Yiwen Yao, Jianmei Ma
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-96
Abstract: C57BL/6?J mice were intraperitoneally injected with either 0.9% saline or lipopolysaccharide (LPS, 5?mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to analyze microglial activation, TNF-α, IL-1β, IL-6, iNOS mRNAs expressions and cellular localization of Cat C in the brain. Nitrite assay was used to examine microglial activation in vitro; RT-PCR and ELISA were used to determine the expression and release of Cat C. Cat C activity was analyzed by cellular Cat C assay kit. Data were evaluated for statistical significance with paired t test.Cat C was predominantly expressed in hippocampal CA2 neurons in C57BL/6?J mice under normal conditions. Six hours after LPS injection, Cat C expression was detected in cerebral cortical neurons; whereas, twenty-four hours later, Cat C expression was captured in activated microglial cells throughout the entire brain. The duration of induced Cat C expression in neurons and in microglial cells was ten days and three days, respectively. In vitro, LPS, IL-1β and IL-6 treatments increased microglial Cat C expression in a dose-dependent manner and upregulated Cat C secretion and its activity.Taken together, these data indicate that LPS and proinflammatory cytokines IL-1β, IL-6 induce the expression, release and upregulate enzymatic activity of Cat C in microglial cells. Further investigation is required to determine the functional role of Cat C in the progression of neuroinflammation, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future.
Neuroinflammation induces glial aromatase expression in the uninjured songbird brain
Kelli A Duncan, Colin J Saldanha
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-81
Abstract: Adult male zebra finches (Taeniopygia guttata) were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA), an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test.Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression.These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.Damage to the homeotherm brain increases aromatase (estrogen synthase) in reactive astroglia [1-3]. Although constitutive aromatase is abundant and neuronal in the undamaged songbird brain, glial aromatase expression is rapidly upregulated following brain damage [1,4-8]. Increased transcription and translation of glial aromatase occurs following damage to the neuropil in songbirds and to a lesser extent in mammals [2,8-10]. In songbirds, this upregulation appears more rapid and robust, since the secondary wave of degeneration characteristic of the mammalian (including human) brain following TBI is only revealed in songbirds following inhibition
Mild hypothermia causes differential, time-dependent changes in cytokine expression and gliosis following endothelin-1-induced transient focal cerebral ischemia
An-Ga?lle Ceulemans, Tine Zgavc, Ron Kooijman, Said Hachimi-Idrissi, Sophie Sarre, Yvette Michotte
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-60
Abstract: The Endothelin-1 (Et-1) model was used to elicit a transient focal cerebral ischemia in male Wistar rats. In this model, the core and penumbra of the insult are represented by the striatum and the cortex respectively. We assessed the effects of 2 hours of hypothermia, started 20 minutes after Et-1 injection on neurological outcome and infarct volume. Furthermore, pro- and anti-inflammatory cytokine expression was determined using ELISA. Microgliosis and astrogliosis were investigated using CD-68 and GFAP staining respectively. All parameters were determined 8, 24, 72 hours and 1 week after the administration of Et-1.Et-1 infusion caused neurological deficit and a reproducible infarct size which increased up to 3 days after the insult. Both parameters were significantly reduced by hypothermia. The strongest reduction in infarct volume with hypothermia, at 3 days, corresponded with increased microglial activation. Reducing the brain temperature affected the stroke induced increase in interleukin-1β and tumor necrosis factor α in the striatum, 8 hours after its induction, but not at later time points. Transforming growth factor β increased as a function of time after the Et-1-induced insult and was not influenced by cooling. Hypothermia reduced astrogliosis at 1 and 3 days after stroke onset.The beneficial effects of hypothermia after stroke on infarct volume and functional outcome coincide with a time-dependent modulation of the cytokine expression and gliosis.Stroke is an important cause of morbidity and mortality in industrialized countries and few therapies exist thus far. It is generally acknowledged that many agents, proven neuroprotective in experimental models, fail in clinical practice, possibly because they cannot respond to the complex multifaceted nature of the ischemic cascade after stroke [1-3]. Hypothermia is a well established and robust neuroprotective treatment and has been the focus of research as it may act on several pathways simultaneously [4,5].
Alzheimer’s Disease: Characterization, Evolution and Implications of the Neuroinflammatory Process [Doen a de Alzheimer: Caracteriza o, Evolu o e Implica es do Processo Neuroinflamatório]
Flávia P. D. Viegas,Maria Cecília R. Sim?es,Miguel D. da Rocha,Maísa R. Castelli
Revista Virtual de Química , 2011,
Abstract: Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by a progressive memory loss and severe cognition decline, associated to degradation of cholinergic neurons in many areas of central nervous system (CNS), with a dramatic reduction in neurotransmitters, specially acetylcholine. The illness progression is also accompanied by behavior changes, leading to individual incapacity and depression, and evolving to dementia and death. AD is related to cerebral aging and located loss of neurons, mainly at hippocampus and basal pro-encephalic tissue. Pathohystologically, AD is characterized by extracellular deposits of senile plaques formed by insoluble fragments of amyloid protein precursor (A ) and intracellular neurofibrillary tangles in the brain, constituted by fragments of hyperphosphorylated TAU protein, with a massive loss in neurons. Despite typical behavior aspects of AD installation, recent studies, especially from the last decade, have evidenced the occurrence of a complex inflammatory process in the neuronal tissue. The relevancy of neuroinflammation in the installation, progression and severity of AD, as well as the mechanisms of immune system activation and key cells in the initial shot of inflammatory cascade in CNS, as microglia and astrocytes, have been demonstrated by important reviews in the literature. Activation of microglia can lead to recruitment of astrocytes that increase the inflammatory response to the extracellular A deposits. This neuroinflammatory component of AD is additionally characterized by a local acute phase response mediated by cytokines, complement cascade activation and induction of an enzymatic inflammatory system, as induced NO synthase (iNOS) and generation of cyclooxygenase 2 (COX-2). Then, astrocytes participate of the degradation and remotion of A , acting as a protective barrier between A deposits and neurons. The multifactorial character of the inflammatory response is characterized by the occurrence of a wide diversity of pro- and anti-inflammatory mediators, some of them being responsible for promotion of neurodegenerative mechanisms, while others could limit the advance of inflammation or exert benefit neurotrophic effects. Therefore, it includes not only a single mediator, but a set of inflammatory agents that would determine the prevalence of benefic or deletery effects during AD progression.
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