China
Africa
Explore chapters and articles related to this topic
Transforming Growth Factor-β: A Cytokine Paradigm
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Michelle R. Frazier-Jessen, Nancy McCartney-Francis, Sharon M. Wahl
Much of our current understanding of the mechanism(s) underlying oral tolerance has been gained from animal models of autoimmune disease that involve immunization of self-proteins, such as experimental autoimmune encephalomyelitis (EAE), which parallels the pathological changes observed in human multiple sclerosis (MS). Characteristic central nervous system (CNS) lesions in both MS and EAE (and in a broader context in the majority of chronic inflammatory disorders) are inflammation, demyelination of nerves by infiltrating macrophages (tissue destruction), and astrocyte proliferation/scarring, which lead to impaired electrical conduction (loss of function) within the CNS. Low-dose oral administration of myelin basic protein (MBP) results in active cellular suppression of MBP-specific T cell proliferation via both CD4+ and CD8+ T cells and dramatically decreases the severity and duration of EAE [48]. This suppression can be adoptively transferred via CD4+ or CD8+ splenic T cells and lasts for several months. Furthermore, chronic, relapsing EAE can be suppressed after disease onset by this therapy. This approach has been effective in the suppression of other experimental autoimmune diseases [49,50], without apparent cytotoxicities.
Central Nervous System Effects of Essential Oil Compounds
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Elaine Elisabetsky, Domingos S. Nunes
Alzheimer's disease (AD) is often modeled by icv administration of amyloid peptides in rodents, causing measurable memory deficits and changes in neuronal tissue (Saito and Saido, 2018). Parkinson's disease (PD) can be modeled by toxins specific to nigrostriatal neurons (e.g., MPTP), locally administered dopamine toxins (e.g., 6-hydroxydopamine), or other neurotoxins (e.g., rotenone), causing motor disturbances and changes in neuronal tissue (Gubellini and Kachidian, 2015). Various methods of depriving the brain or neuronal cells of oxygen and glucose (oxygen-glucose deprivation, OGD) in vitro (cultures), ex vivo (brain slices), or in vivo (artery occlusion models) mimic ischemia or stroke and provide the possibility to follow cellular events and changes in biochemical pathways that follow (Hansel et al., 2015). Modifications include disturbances of cell calcium homeostasis; depletion of adenine nucleotides; activation of phospholipases, proteases, and endonucleases; and the generation of free radicals (ROS). All of these steps and related pathways are considered potential targets for drug intervention and constitute endpoints in the assessment neuroprotective effects of drugs (Bellaver et al., 2015). Multiple sclerosis (MS) is characterized by inflammation, demyelination, axonal loss, and gliosis. The experimental autoimmune encephalomyelitis (EAE) is the most commonly used MS model (Constantinescu et al., 2011).
Commensal microbiota and its relationship to homeostasis and disease
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Jonathan Braun, Elaine Y. Hsiao, Nicholas Powell
Although one might intuitively anticipate that intestinal microbes exert influence over helper T-cell polarization in the gut, it is more surprising that gut microbes can modulate extraintestinal T-cell responses. Germ-free mice have impaired immunity and increased susceptibility to particular infections. However, they are also less sensitive to T-cell–mediated autoimmune conditions. Experimental allergic encephalomyelitis (EAE) is a frequently studied animal model of autoimmunity that mirrors aspects of human multiple sclerosis. Disease is mediated by T cells responding to antigens present on the myelin sheath that coats nerves. EAE can be induced in rodents and primates by immunization with nerve tissue–derived proteins or peptides, such as myelin basic protein or myelin oligodendrocyte glycoprotein in adjuvant. About 2 weeks after immunization, mice develop relapsing and remitting symptoms of weakness and paralysis. EAE is characterized by expansion of TH17 and TH1 cells in inflamed nerve tissue. It has been shown that germ-free mice are much less sensitive to EAE induction than mice colonized with a conventional intestinal microflora. Many germ-free mice failed to develop any neurologic features. EAE resistance in germ-free mice is associated with an attenuated inflammatory response. These experiments strongly implied that gut microbes are necessary for at least some pathogenic T-cell responses outside the gut (Figure 19.5).
Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis
Published in Gut Microbes, 2022
Dušan Radojević, Marina Bekić, Alisa Gruden-Movsesijan, Nataša Ilić, Miroslav Dinić, Aleksandar Bisenić, Nataša Golić, Dragana Vučević, Jelena Đokić, Sergej Tomić
The capacity of MDSCs to suppress inflammation in vivo was evaluated on a model of EAE described previously.18 Briefly, female DA rats eight-week-old, with body weights ranging from 138 to 166 g, were randomly divided into three groups, each group containing 10 animals weighted similarly. DA rats were anesthetized with ketamine/xylazine and then immunized with spinal cord homogenate (50% w/v in saline) emulsified in complete Freund’s adjuvant (CFA) containing 4 mg/ml Mycobacterium tuberculosis (Difco/BD Diagnostics, Sparks, MD, USA) administered to the right-hind footpad. One day after immunization, one group received BM-derived MDSCs (2 × 106 cells/rat) and one group received the same number of MDSC-PGE2 intraperitoneally. From day 8 post-immunization, the animals were weighed and assessed for signs of the disease daily and scored according to the following scale:0, no clinical signs; 1, flaccid tail; 2, hind limb paresis; 3, complete bilateral hind limb paralysis often associated with incontinence; and 4, moribund state or death. Intermediate scores were assigned if neurological signs were of lower severity than typically observed. Several disease parameters were examined to evaluate the severity of EAE, including incidence, mean day of onset, duration of illness, mean maximal severity score, and cumulative disease index (the sum of the daily mean clinical scores for a group over a given number of days). Animals were observed for 27 days after immunization. All experiments were repeated twice.
Eosinophilic annular erythema
Published in Baylor University Medical Center Proceedings, 2021
Nicole Dacy, Kyle Oney, Katherine Fiala, Palak Parekh
After her diagnosis of EAE, our patient was evaluated by allergy, infectious disease, hematology/oncology, and plastic surgery to look for possible contributing factors. Computed tomography of her chest, abdomen, and pelvis was unremarkable with no concern for an underlying lymphoproliferative disorder. Her breast implants were evaluated and were found to be intact. She was no longer working in an environment with possible mold exposure, and a systemic fungal infection workup was negative. The patient was treated empirically for Helicobacter pylori with triple therapy. She is currently on prednisone 20 mg daily to control symptoms; high-dose prednisone clears her lesions. She has been taking hydroxychloroquine 200 mg twice a day for 4 months and is planned to start dapsone or dupilumab if there is no improvement.
Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota
Published in Gut Microbes, 2020
Xin-Yu Lu, Bing Han, Xin Deng, Si-Ying Deng, Yan-Yan Zhang, Pei-Xin Shen, Teng Hui, Rui-Heng Chen, Xing Li, Yuan Zhang
Female C57BL/6 mice (~8 weeks) were purchased from SPF (Beijing) Biotechnology CO., ltd. Mice were housed at the in-house animal care facility of Shaanxi Normal University animal under a 12-hour day-night-cycle and standardized conditions (23°C ± 2°C). All experiments were approved by the Institutional Animal Care and Use committee of Shaanxi Normal University and were in accordance with the approved institutional guidelines and regulations. EAE was induced according to our previous study.19,20 EAE mice were randomly divided into two treatment groups, 100 mg/kg PPE or solvent (PBS) were applied daily via oral gavage, at the first day of immunization, onset of disease (10 d), and peak of disease (16 d). After immunization, mice were assessed clinically in a blinded manner using a disease severity scale that is scored according to a 0–5 scale as described previously.20 Briefly, 0, no clinical symptoms; 0.5, stiff tail; 1, limp tail; 1.5, limp tail and stagger gait; 2, paralysis of one limb; 2.5, one limb was paralyzed and the other was faint; 3, both hind limbs were completely paralyzed; 4, moribund; and 5, death.