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Updated: Oct 15, 2025
Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
(R)-ketamine ameliorates the progression of experimental autoimmune encephalomyelitis in mice
Xingming Wang1, Lijia Chang1, Yunfei Tan1
1Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Abstract:
Multiple sclerosis (MS) is an immune-mediated neurological disease that attacks the central nervous system, including spinal cord and brain. Experimental autoimmune encephalomyelitis (EAE) is the most commonly used model for MS. Depression is the most prevalent comorbidity in MS patients. We previously demonstrated that (R)-ketamine would be a novel antidepressant without side effects of ketamine. This study was undertaken to investigate whether (R)-ketamine could attenuate disease progression in EAE mouse model. (R)-ketamine (10 mg/kg/day for 15 days) significantly attenuated the reduction of body weight in EAE model mice compared to saline-treated mice. Furthermore, (R)-ketamine ameliorated the clinical EAE scores compared to saline-treated mice. Moreover, (R)-ketamine significantly attenuated the marked increases in the pathological scores, microglial activation, and blood-brain barrier integrity in the spinal cord compared to saline-treated mice. In conclusion, the current study suggests that (R)-ketamine could ameliorate EAE clinical scores and pathological changes in the spinal cord of EAE mice. Therefore, it is likely that (R)-ketamine would be a new potential prophylactic drug for MS.
Insights
(R)-ketamine, a novel antidepressant, significantly reduced disease progression in a mouse model of Multiple Sclerosis (MS). This compound attenuated clinical symptoms and spinal cord pathology, suggesting potential as a prophylactic treatment for MS.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple Sclerosis (MS) is a debilitating immune-mediated neurological disease affecting the central nervous system.
- Depression is a common comorbidity in MS patients.
- Experimental Autoimmune Encephalomyelitis (EAE) serves as a primary animal model for MS research.
Purpose of the Study:
- To investigate the therapeutic potential of (R)-ketamine in mitigating disease progression in the EAE mouse model.
- To evaluate (R)-ketamine's efficacy in reducing clinical symptoms and neuropathological changes associated with EAE.
Main Methods:
- Mice with EAE were treated with (R)-ketamine (10 mg/kg/day for 15 days) or saline.
- Evaluated body weight, clinical EAE scores, spinal cord pathology, microglial activation, and blood-brain barrier integrity.
Main Results:
- (R)-ketamine treatment significantly attenuated body weight loss in EAE mice compared to controls.
- (R)-ketamine administration ameliorated clinical EAE scores and reduced pathological changes in the spinal cord.
- The treatment also attenuated microglial activation and preserved blood-brain barrier integrity in the spinal cord.
Conclusions:
- (R)-ketamine demonstrates significant therapeutic effects in the EAE mouse model, ameliorating both clinical and pathological manifestations.
- These findings suggest that (R)-ketamine holds promise as a novel prophylactic agent for Multiple Sclerosis.
