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Updated: Aug 9, 2026
Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007
Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune
E Wallström1, P Diener, A Ljungdahl
1Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Abstract:
Memantine, a clinically employed drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rat experimental autoimmune encephalomyelitis (EAE). Interestingly, this therapeutic effect was not due to dampened CNS inflammation, as assessed by immunohistochemical evaluation of spinal cord tissue. Furthermore, numbers of interferon gamma (IFN gamma) mRNA expressing cells were not decreased, as assessed by in situ hybridization. Systemic immunity in terms of numbers of IFN gamma secreting cells in response to immunodominant myelin basic protein (MBP) peptides ex vivo was not reduced, and non-toxic doses of memantine did not affect lymphocyte proliferation or IFN gamma secretion in vitro. Considering these findings, we hypothesize that effector mechanisms responsible for reversible neurological deficits in EAE may involve NMDA receptors, and this highlights neurons as targets during autoimmune neuroinflammation.
Insights
Memantine ameliorates neurological deficits in experimental autoimmune encephalomyelitis (EAE) by targeting neurons via N-methyl-D-aspartate (NMDA) receptors, not by reducing inflammation or immune cell activity.
Area of Science:
- Neuroimmunology
- Pharmacology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis.
- N-methyl-D-aspartate (NMDA) receptors are implicated in neurological function.
Purpose of the Study:
- To investigate the therapeutic effects of memantine in a Lewis rat EAE model.
- To elucidate the mechanisms underlying memantine's efficacy in EAE.
Main Methods:
- Administration of memantine to Lewis rats with EAE.
- Immunohistochemical and in situ hybridization analysis of spinal cord tissue.
- Ex vivo and in vitro assessment of immune cell function.
Main Results:
- Memantine dose-dependently improved neurological deficits in EAE rats.
- No significant reduction in central nervous system inflammation was observed.
- Interferon gamma (IFN-gamma) mRNA expression and IFN-gamma secretion by lymphocytes were not decreased.
- Memantine did not affect lymphocyte proliferation or IFN-gamma secretion in vitro.
Conclusions:
- The therapeutic effects of memantine in EAE are not mediated by anti-inflammatory or immunosuppressive mechanisms.
- Neurological deficits in EAE may involve NMDA receptor-dependent mechanisms.
- Neurons are potential targets during autoimmune neuroinflammation in EAE.
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