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Updated: Jun 18, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
Initiation and progression of axonopathy in experimental autoimmune encephalomyelitis
Athena M Soulika1, Eunyoung Lee, Erica McCauley
1Institute for Pediatric Regenerative Medicine, University of California Davis School of Medicine, Sacramento, California 95817, USA.
Abstract:
Axonal loss is the principal cause of chronic disability in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). In C57BL/6 mice with EAE induced by immunization with myelin oligodendrocyte glycoprotein peptide 35-55, the first evidences of axonal damage in spinal cord were in acute subpial and perivascular foci of infiltrating neutrophils and lymphocytes and included intra-axonal accumulations of the endovesicular Toll-like receptor TLR8, and the inflammasome protein NAcht leucine-rich repeat protein 1 (NALP1). Later in the course of this illness, focal inflammatory infiltrates disappeared from the spinal cord, but there was persistent activation of spinal cord innate immunity and progressive, bilaterally symmetric loss of small-diameter corticospinal tract axons. These results support the hypothesis that both contact-dependent and paracrine interactions of systemic inflammatory cells with axons and an innate immune-mediated neurodegenerative process contribute to axonal loss in this multiple sclerosis model.
Insights
Axonal loss in multiple sclerosis models involves early inflammatory cell infiltration and later innate immune activation, leading to progressive nerve damage and disability. Understanding these mechanisms is key to developing new treatments.
Area of Science:
- Neuroimmunology
- Pathology
Background:
- Axonal loss is a primary driver of chronic disability in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).
- Identifying the precise mechanisms of axonal damage in EAE is crucial for understanding MS pathogenesis.
Purpose of the Study:
- To investigate the early and late pathological changes in the spinal cord during EAE.
- To elucidate the role of innate immunity and inflammatory cell interactions in axonal degeneration.
Main Methods:
- Induction of EAE in C57BL/6 mice using myelin oligodendrocyte glycoprotein peptide 35-55.
- Histopathological analysis of spinal cord tissue to identify inflammatory infiltrates and axonal damage markers.
- Assessment of innate immune activation and specific molecular targets like Toll-like receptor 8 (TLR8) and NALP1.
Main Results:
- Early EAE stages showed subpial and perivascular inflammatory foci with neutrophils and lymphocytes, containing intra-axonal TLR8 and NALP1.
- Later EAE stages exhibited resolution of focal infiltrates but persistent spinal cord innate immune activation.
- Progressive, bilateral loss of small-diameter corticospinal tract axons was observed.
Conclusions:
- Axonal loss in EAE results from both direct inflammatory cell interactions with axons and a sustained, innate immune-mediated neurodegenerative process.
- These findings support a dual mechanism contributing to axonal damage in this MS model.
- Targeting both inflammatory and innate immune pathways may be beneficial for treating MS-related axonal loss.
