scholarly journals Allergic Rhinitis in Rats Is Associated with an Inflammatory Response of the Hippocampus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Shasha Yang ◽  
Jing Wu ◽  
Qinxiu Zhang ◽  
Xinrong Li ◽  
Daien Liu ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Inflammatory Responses ◽  
Brain Regions ◽  
Abnormal Behavior ◽  
Neurological Deficits ◽  
Glial Fibrillary Acid Protein ◽  
Adult Rats ◽  
Memory Decline ◽  
Acid Protein ◽  
And Behavior

Allergic rhinitis (AR) is a major concern in personal and public health, which negatively affects emotions and behavior, leading to cognitive deficits, memory decline, poor school performance, anxiety, and depression. Several cellular and molecular mediators are released in the inflammatory process of AR and activate common neuroimmune mechanisms, involving emotionally relevant circuits and the induction of anxiety. Responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to allergic processes have been reported, which may also include responsiveness of the hippocampus, cortex, and other brain regions. Here, we have used an optimized rat model of AR to explore whether the disease has a relationship with inflammatory responses in the hippocampus. AR was established in adult rats by ovalbumin sensitization, and the expression of various inflammatory substances in the hippocampus was measured by specific assays. Comparison between experimental and various control groups of animals revealed an association of AR with significant upregulation of substance P, microglia surface antigen (CD11b), glial fibrillary acid protein (GFAP), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) in the hippocampus. Thus, we hypothesize that the AR challenge may activate these inflammatory mediators in the hippocampus, which in turn contribute to the abnormal behavior and neurological deficits associated with AR.

Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine

2018 ◽  
Vol 205 (2) ◽  
pp. 105-119
Author(s):  
Rasha B. Abd-ellatief ◽  
Heba K. Mohamed ◽  
Hassan I. Kotb
Keyword(s):  
Pain Perception ◽  
Inflammatory Responses ◽  
Light And Electron Microscopy ◽  
Glial Fibrillary Acid Protein ◽  
Peripheral Sensitization ◽  
Reactive Astrogliosis ◽  
Acid Protein ◽  
Tnf Α ◽  
Oxide Synthase ◽  
Chronic Muscle Pain

To our knowledge, this is the first study which investigates the induction of neuroinflammation in rats using an acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception, and astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory responses induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by intramuscular injection of 100 µL of acidic saline on days 0 and 5 resulted in peripheral sensitization (measured using the von Frey test) and significant (p < 0.05) increases in IL-1β (160.2 ± 1.1 to 335.2 ± 1.8), IL-6 (100.1 ± 1.4 to 202.4 ± 1.1), and TNF-α (60.0 ± 0.7 to 115.5 ± 1). Light and electron microscopy revealed degenerative changes in the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of glial fibrillary acid protein and inducible nitric oxide synthase. Surprisingly, treatment with a single dose of an α2-adrenergic agonist, dexmedetomidine (5 µg/kg i.p.), attenuated these changes. This trial suggests that dexmedetomidine possibly directly acts on astrocytes, and a peripheral action is also suggested.

scholarly journals Inter-alpha Inhibitor Proteins Modulate Neuroinflammatory Biomarkers After Hypoxia-Ischemia in Neonatal Rats

2019 ◽  
Vol 78 (8) ◽  
pp. 742-755 ◽  
Author(s):  
Adriel Barrios-Anderson ◽  
Xiaodi Chen ◽  
Sakura Nakada ◽  
Ray Chen ◽  
Yow-Pin Lim ◽  
...  
Keyword(s):  
Brain Injury ◽  
Peripheral Blood ◽  
Calcium Binding ◽  
Brain Regions ◽  
Female Rats ◽  
Glial Fibrillary Acid Protein ◽  
Acid Protein ◽  
Neurobehavioral Outcomes ◽  
Cellular Markers ◽  
Complete Blood Counts

AbstractNeuroinflammation contributes to hypoxic-ischemic (HI) brain injury. Inter-alpha inhibitor proteins (IAIPs) have important immunomodulatory properties. Human (h) plasma-derived IAIPs reduce brain injury and improve neurobehavioral outcomes after HI. However, the effects of hIAIPs on neuroinflammatory biomarkers after HI have not been examined. We determined whether hIAIPs attenuated HI-related neuroinflammation. Postnatal day-7 rats exposed to sham-placebo, or right carotid ligation and 8% oxygen for 90 minutes with placebo, and hIAIP treatment were studied. hIAIPs (30 mg/kg) or PL was injected intraperitoneally immediately, 24, and 48 hours after HI. Rat complete blood counts and sex were determined. Brain tissue and peripheral blood were prepared for analysis 72 hours after HI. The effects of hIAIPs on HI-induced neuroinflammation were quantified by image analysis of positively stained astrocytic (glial fibrillary acid protein [GFAP]), microglial (ionized calcium binding adaptor molecule-1 [Iba-1]), neutrophilic (myeloperoxidase [MPO]), matrix metalloproteinase-9 (MMP9), and MMP9-MPO cellular markers in brain regions. hIAIPs reduced quantities of cortical GFAP, hippocampal Iba-1-positive microglia, corpus callosum MPO, and cortical MMP9-MPO cells and the percent of neutrophils in peripheral blood after HI in male, but not female rats. hIAIPs modulate neuroinflammatory biomarkers in the neonatal brain after HI and may exhibit sex-related differential effects.

scholarly journals Standardized Method for the Assessment of Behavioral Responses of Zebrafish Larvae

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 884
Author(s):  
Hideyuki Maeda ◽  
Noritoshi Fukushima ◽  
Akihiro Hasumi
Keyword(s):  
Early Stage ◽  
Scientific Evidence ◽  
Video Tracking ◽  
Abnormal Behavior ◽  
Laboratory Setting ◽  
Zebrafish Larvae ◽  
Experimental Systems ◽  
Standardized Method ◽  
Life Phenomena ◽  
And Behavior

Zebrafish are easy to breed in a laboratory setting as they are extremely fertile and produce dozens of eggs per set. Because zebrafish eggs and the skin of the early-stage larvae are transparent, their embryos and the hearts and muscles of their larvae can be easily observed. Multiple rapid analyses of heart rate and behavior can be performed on these larvae simultaneously, enabling investigation of the influence of neuroactive substances on abnormal behavior, death, and associated pathogenetic mechanisms. Zebrafish larvae are becoming increasingly popular among researchers and are used in laboratories worldwide to study various vertebrate life phenomena; more experimental systems using zebrafish will undoubtedly be developed in the future. However, based on the available literature, we believe that the conceptualization of a protocol based on scientific evidence is necessary to achieve standardization. We exposed zebrafish larvae at 6–7 days post-fertilization to 50 repeated light–dark stimuli at either 15-min or 5-min intervals. We measured the traveled distance and habituation time through a video tracking apparatus. The traveled distance stabilized after the 16th repetition when the zebrafish were exposed to light–dark stimuli at 15-min intervals and after the 5th repetition when exposed at 5-min intervals. Additionally, at 15-min intervals, the peak of the traveled distance was reached within the first minute in a dark environment, whereas at 5-min intervals, it did not reach the peak even after 5 min. The traveled distance was more stable at 5-min intervals of light/dark stimuli than at 15-min intervals. Therefore, if one acclimatizes zebrafish larvae for 1 h and collects data from the 5th repetition of light/dark stimuli at intervals of 5 min in the light/dark test, a stable traveled distance result can be obtained. The establishment of this standardized method would be beneficial for investigating substances of unknown lethal concentration.

scholarly journals The effect of Co-Q10 on allergic rhinitis and allergic asthma

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Qixue Du ◽  
Wei Meng ◽  
Seyyed Shamsadin Athari ◽  
Renzhong Wang
Keyword(s):  
Allergic Rhinitis ◽  
Animal Models ◽  
Allergic Asthma ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Inflammatory Factors ◽  
Stress Injury ◽  
Antioxidant Genes ◽  
Histamine Production ◽  
Nrf2 Expression

Abstract Background Allergic asthma is an inflammatory disease resulting from continued or intermittent allergen exposure, and allergic rhinitis can be trigger of asthma. The main mechanism of these disease is allergic reaction and immune response dysregulation. Co-Q10 is an enzyme cofactor in mitochondria can control asthma and allergic rhinitis symptoms. In the present study, we determined that the CoQ10-induced anti-allergic effects were mediated by up-regulation of Nrf2. Methods Animal models of allergic rhinitis and allergic asthma were produced and treated with Co-Q10, Co-Q10 and O-3, Co-Q10 and Mg-S. Bronchoalveolar lavage fluid was collected from animal models, and IL-4, 5, 13, INF-y, Eicosanoids, IgE, EPO, and histamine production were measured. Also, COX-2, CCL24, CCL11, Nrf2, Eotaxin, Cytb, COX1 and ND1 genes expressions and histopathology were studied. BALf's cells were collected by tracheostomy and used in slide producing by cytospine. Cytokines, Eicosanoids, IgE, EPO, and histamine were measured by ELISA method. Gene expression was done by Real-time PCR. Results Co-Q10 with two supplementation (Mg-S and O-3) modulate MRC, BALf eosinophils, eosinophilic inflammation related genes (eotaxin, CCL11 and CCL24), peribronchial and perivascular inflammation, EPO, type 2 cytokines (IL-4, 5 and 13), IgE, histamine, Cyc-LT and LTB4 as main allergic bio-factors. Importantly, Co-Q10 treatment increased Nrf2 expression and Nrf2 induced antioxidant genes, glutathione redox and inhibited inflammation, oxidative stress injury, Th2 cytokines production and attenuated allergic inflammatory responses. Conclusion Nrf2 is activated in response to allergen, induces resistance against the rhinitis and asthma development and plays an essential role in broncho-protection. Co-Q10 increases the Nrf2 expression and the Nrf2 over-expression has strong effect in control of type2 cytokines, allergic mediators and inflammatory factors that lead to harnessing of allergy and asthma. Graphic abstract

Gliomatosis Cerebri in Six Dogs

2003 ◽  
Vol 40 (1) ◽  
pp. 97-102 ◽  
Author(s):  
B. Porter ◽  
A. DeLahunta ◽  
B. Summers
Keyword(s):  
Cranial Nerve ◽  
Gliomatosis Cerebri ◽  
Clinical Findings ◽  
Human Medicine ◽  
Glial Fibrillary Acid Protein ◽  
Neoplastic Cells ◽  
Diffuse Infiltration ◽  
Acid Protein ◽  
Pathologic Features ◽  
The Brain

Gliomatosis cerebri is a well-recognized entity in human medicine characterized by unusually widespread infiltration of the neuraxis by neoplastic glial cells with relative preservation of brain architecture. This report describes the pathologic features of the disease in six dogs. The dogs ranged from 3 to 9 years of age (mean 6.1 years) without evidence of breed predilection; five of the six dogs were neutered or intact males. The clinical findings were mixed (including depression, circling, cranial nerve deficits), reflecting the diffuse nature of the disease. Histologically, there was remarkably diffuse infiltration of the white and gray matter of the brain by small numbers of elongated neoplastic cells. Areas of greater cellularity formed grossly visible lesions in four cases. Anisocytosis and pleomorphism were greater in areas of higher cellularity. Other features of tumor growth included subpial accumulation, neuronal satellitosis, perivascular cuffing, and tropism for cranial nerve and brain stem nuclei. Neoplastic cells were negative on immunohistochemical stains for glial fibrillary acid protein (GFAP) and leukocyte markers, reflecting the uncertain histogenesis of these unusual neoplasms.

Role of Superantigens in Allergic Inflammation: Their Relationship to Allergic Rhinitis, Chronic Rhinosinusitis, Asthma, and Atopic Dermatitis

2018 ◽  
Vol 32 (6) ◽  
pp. 502-517 ◽  
Author(s):  
Nuray Bayar Muluk ◽  
Fazilet Altın ◽  
Cemal Cingi
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Inflammatory Response ◽  
Chronic Rhinosinusitis ◽  
Inflammatory Responses ◽  
Immunoglobulin E ◽  
Severe Disease ◽  
Allergic Inflammation ◽  
Allergic Dermatitis

Objectives Our intention was to review all material published to date regarding superantigens (SAgs) and allergy from an otorhinolaryngological viewpoint to understand this association more clearly. Methods We identified all materials published mentioning both SAg and allergic rhinitis (AR), chronic sinusitis, asthma, and atopic dermatitis (AD) that are indexed on PubMed, Google, or the ProQuest Central databases. Results Staphylococcus aureus is a significant bacterial pathogen in humans and has the ability to produce enterotoxins with superantigenic features. The inflammatory response in allergy seen in both B cell and T cell may be attributed to SAgs. Sufferers of both allergic asthma with rhinitis and AR alone produce serological evidence of immunoglobulin E formation to SAgs produced by S. aureus. Perennial AR sufferers carry S. aureus more frequently and the presence of the organism within the nasal cavity may exacerbate perennial AR. SAg produced by S. aureus potentially worsens the asthmatic inflammatory response within the airway and may lead to the airways becoming hyperresponsive, as well as possibly activating T cells if asthmatic control is poor. Staphylococcal SAgs potentially increase the risk of developing chronic rhinosinusitis with nasal polyposis, additionally being a marker for more severe disease. If SAgs bring about chronic inflammatory responses in the nose and sinuses, then T cells excreting interferon-gamma may be a crucial mediator. In allergic dermatitis, S. aureus could be a key player in exacerbation of the condition. Even in younger pediatric patients with allergic dermatitis, allergic hypersensitivity to SAgs is frequent and may be a factor explaining how severe the condition becomes. Conclusion Just as SAgs are known to feature in many allergic conditions, they play their part in AR, chronic rhinosinusitis, asthma, and AD. Further research is required before the relationship between SAgs and allergy can be adequately explained.

scholarly journals DEXAMETHASONE NEUROPROTECTION IS ASSOCIATED WITH PRESERVED EXPRESSION OF BCL-2 AND SUPPRESSION OF GLIAL FIBRILLARY ACID PROTEIN (GFAP). ▴ 1226

1996 ◽  
Vol 39 ◽  
pp. 207-207
Author(s):  
Paul G Ekert ◽  
Neil MacLusky ◽  
Larry Becker ◽  
Martin Post ◽  
A. Keith Tanswell
Keyword(s):  
Glial Fibrillary Acid Protein ◽  
Acid Protein

scholarly journals Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex

2021 ◽  
Author(s):  
Sierra A. Codeluppi ◽  
Dipashree Chatterjee ◽  
Thomas D. Prevot ◽  
Keith A. Misquitta ◽  
Etienne Sibille ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Fluorescent Protein ◽  
Glial Fibrillary Acid Protein ◽  
Behavioral Deficits ◽  
Sholl Analysis ◽  
Acid Protein ◽  
Potential Link ◽  
Green Fluorescent ◽  
Stress Models

AbstractBackgroundNeuromorphological changes are consistently reported in the prefrontal cortex (PFC) of patients with stress-related disorders and in rodent stress models, but the effects of stress on astrocyte morphology and potential link to behavioral deficits are relatively unknown.MethodsTo answer these questions, transgenic mice expressing green fluorescent protein (GFP) under the glial fibrillary acid protein (GFAP) promotor were subjected to 7, 21 or 35 days of chronic restraint stress (CRS). CRS behavioral effects on anhedonia- and anxiety-like behaviours were measured using the sucrose intake and the PhenoTyper tests, respectively. PFC GFP+ or GFAP+ cells morphology was assessed using Sholl analysis and associations with behavior were determined using correlation analysis.ResultsCRS-exposed mice displayed anxiety-like behavior at 7, 21 and 35 days and anhedonia-like behavior at 35 days. Analysis of GFAP+ cell morphology revealed significant atrophy of distal processes following 21 and 35 days of CRS. CRS induced similar decreases in intersections at distal radii for GFP+ cells, accompanied by increased proximal processes. Additionally, the number of intersections at the most distal radius step significantly correlated with time spent in the shelter zone in the PhenoTyper test (r=-0.581, p<0.01) for GFP+ cells and with behavioural emotionality calculated by z-scoring all behavioral measured deficits, for both GFAP+ and GFP+ cells (r=-0.400, p<0.05; r=-0.399, p<0.05).ConclusionChronic stress exposure induces a progressive atrophy of cortical astroglial cells, potentially contributing to maladaptive neuroplastic changes associated with stress-related disorders.

scholarly journals Target Occupancy Study and Whole-Body Dosimetry with a MAGL PET Ligand 11C-PF-06809247 in non-human Primates

2021 ◽  
Author(s):  
Ryosuke Arakawa ◽  
Akihiro Takano ◽  
Sangram Nag ◽  
Zhisheng Jia ◽  
Nahid Amini ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Input Function ◽  
Brain Regions ◽  
Whole Body ◽  
Dependent Manner ◽  
Serine Hydrolase ◽  
Cynomolgus Monkeys ◽  
Pretreatment Condition ◽  
Body Distribution ◽  
Pretreatment Conditions

Abstract BackgroundMonoacylglycerol lipase (MAGL) is a key serine hydrolase which terminates endocannabinoid signaling and regulates arachidonic acid driven inflammatory responses within the central nervous system (CNS). To develop [11C]PF-06809247 into a clinically usable positron emission tomography (PET) radioligand, we assessed the brain target occupancy of a MAGL inhibitor using non-human primate (NHP). Additionally, we measured the whole-body distribution of [11C]PF-06809247 in NHP and estimated human effective radiation doses.MethodsSeven cynomolgus monkeys were enrolled for brain PET measurements. Two PET measurements were performed in each NHP: one baseline and one pretreatment condition with intravenous administration of PF-06818883, a selective MAGL inhibitor, (total of seven doses between 0.01-1.27 mg/kg). Kinetic parameters K1, k2 and k3 were estimated by an irreversible two tissue compartment (2TC) model using metabolite corrected plasma radioactivity as the input function. Ki by 2TC and Patlak analysis were calculated. The target occupancy was calculated using Ki at baseline and pretreatment conditions. Two cynomolgus monkeys were enrolled for whole-body PET measurements. Estimates of the absorbed radiation dose in humans were calculated with OLINDA/EXM 1.1 using the adult male reference model.ResultsRadioactivity was decreased in all brain regions following pretreatment with PF-06818883. Occupancy was measured as 25.4%-100.5% in a dose dependent manner. Whole-body PET showed high uptake values in the liver, small intestine, kidney, and brain. The effective dose was calculated as 4.3 μSv/MBq.Conclusions[11C]PF-06809247 is a promising PET ligand for further MAGL studies in human brain.

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