Name: induction and diverse assessment indicators of experimental autoimmune encephalomyelitis
Uploaded: 2022-09-09T12:30:00
Description: Watch this Scientific Journal Video about Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis at JoVE.com

The authors acknowledge the support from the National Natural Science Foundation of China (32070768, 31871404, 31900658, 32270754) and the State Key Laboratory of Drug Research.

The Animal Care Committee of Tongji University approved the present work, and all animal care guidelines were followed. Male or female C57BL/6J mice between 8-12 weeks of age were used for the experiments. It was ensured that the age and sex were the same in the experimental groups; otherwise, the susceptibility to the disease was affected. Mice were housed in a specific pathogen-free environment with alternating 12 h light and dark cycles under constant conditions (room temperature 23 &#177; 1 &#176;C, humidity 50% &#17...

MS is a demyelinating inflammatory disease of the CNS and is one of the most common neurological disorders causing chronic disability in young people, imposing a huge burden on families and society3,4. MS has always been classified as an organ-specific T cell-mediated autoimmune disease, inducing the autoimmune system to slowly erode CNS, which will involve multiple systems throughout the body27. Typical clinical symptoms include visual im...

Autoimmune diseases are a spectrum of disorders caused by the immune system&#39;s immune response to its own antigens resulting in tissue damage or dysfunction1. Multiple sclerosis (MS) is a chronic autoimmune disease of polyneuropathy in the central nervous system (CNS), characterized by inflammatory infiltration, demyelination, and neuronal axonal degeneration2,3. At present, MS has affected as many as 2.5 million people around the world, mostly young and middle-aged people aged 20-40, who are often the backbone of their families and society. This has caused considerable impact and harm to families and society2,4.
MS is a multifactorial disease with diverse and complex clinical manifestations. In addition to classic neurological disorders characterized by inflammatory infiltration and demyelination, MS often shows visual impairment, limb dyskinesia, and cognitive and emotional disorders5,6,7. If MS patients do not get the proper and correct treatment, half of them will live in wheelchairs after 20 years, and nearly half of them will experience depressive and anxiety symptoms, leading to much higher levels of suicidal ideation than the general population8,9.
Despite a long research period, the etiology of MS remains elusive, and the pathogenesis of MS has not yet been elucidated. Animal models of MS have allowed serving as testing tools to explore disease development and new therapeutic approaches, despite the significant differences between the rodent and human immune systems, while at the same time sharing some basic principles. Experimental autoimmune encephalomyelitis (EAE) is currently the ideal animal model for studying MS, which uses autoantigen immunity from myelin proteins to induce autoimmunity to CNS components in susceptible mice, with the addition of complete Freund&#39;s adjuvant (CFA) and pertussis toxin (PTX) to enhance the humoral immune response. Depending on the genetic background and immune antigens, different disease processes, including acute, relapsing-remitting, or chronic, are obtained to mimic various clinical forms of MS10,11,12. The relevant immunogens commonly used in the construction of EAE models come from self-CNS proteins, such as myelin basic protein (MBP), proteolipid protein (PLP), or myelin oligodendrocyte glycoprotein (MOG). MBP- or PLP-immunized SJL/L mice develop a relapsing-remitting course, and MOG triggers chronic progressive EAE in C57BL/6 mice11,12,13.
The main purpose of disease-modifying therapy (DMT) is to minimize disease symptoms and improve function6. Several drugs are used clinically to alleviate MS, but no drug has yet been used to completely cure it, revealing the necessity of synergistic treatment. C57BL/6 mice are currently the most commonly used to construct transgenic mice, and in this work, an EAE model induced by MOG35-55 in C57BL/6J mice with a 5-point scale was used to monitor the disease progression. EAE models also suffer from anxiety-like moods and bone loss, and the widely known demyelinating lesions. Here, the method to assess the symptoms of EAE from multiple perspectives using open-field test and micro-computed tomography (Micro-CT) analysis is also described.

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induction and diverse assessment indicators of experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a typical autoimmune disease of the central nervous system (CNS) characterized by inflammatory infiltration, demyelination, and axonal damage. Currently, there are no measures to cure MS completely, but multiple disease-modifying therapies (DMT) are available to control and mitigate disease progression. There are significant similarities between the CNS pathological features of experimental autoimmune encephalomyelitis (EAE) and MS patients. EAE has been widely used as a representative model to determine MS drugs' efficacy and explore the development of new therapies for MS disease. Active induction of EAE in mice has a stable and reproducible effect and is particularly suitable for studying the effects of drugs or genes on autoimmune neuroinflammation. The method of immunizing C57BL/6J mice with myelin oligodendrocyte glycoprotein (MOG35-55) and the daily assessment of disease symptoms using a clinical scoring system is mainly shared. Given the complex etiology of MS with diverse clinical manifestations, the existing clinical scoring system can't satisfy the assessment of disease treatment. To avoid the shortcomings of a single intervention, new indicators to assess EAE based on clinical manifestations of anxiety-like moods and osteoporosis in MS patients are created to provide a more comprehensive assessment of MS treatment.

After immunization of the mice, the bodyweight of the mice is recorded daily, and their clinical symptoms are evaluated according to the protocol described above (step 4). In C57BL/6J mice immunized with MOG peptide, because the location of the lesion is mainly confined to the spinal cord,the pathogenesis of EAE mice spreads from the tail end to the head. At the beginning of the disease, EAE mice exhibit weakness and drooping of the tail, followed by weakness of the hind limbs, uncoordinated movement, and paralysis. As t...

Watch this Scientific Journal Video about Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis at JoVE.com

Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis

The present protocol describes the induction of experimental autoimmune encephalomyelitis in a mouse model using myelin oligodendrocyte glycoprotein and monitoring the disease process using a clinical scoring system. Experimental autoimmune encephalomyelitis-related symptoms are analyzed using mouse femur micro-computed tomography analysis and open field test to assess the disease process comprehensively.

Multiple sclerosis (MS) is a typical autoimmune disease of the central nervous system (CNS) characterized by inflammatory infiltration, demyelination, and ...

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