Mouse model mimics multiple sclerosis in the clinico-radiological paradox

Area of Science:

• Neuroimmunology
• Neuroimaging
• Animal Models of Disease

Background:

• Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for studying multiple sclerosis (MS).
• The utility of EAE in predicting diagnostic and therapeutic strategies for MS has been recently questioned.
• Early pathological changes in EAE, particularly their distribution and correlation with clinical presentation, require further elucidation.

Purpose of the Study:

• To investigate the early distribution and characteristics of lesions in a murine adoptive transfer EAE model using advanced MRI techniques.
• To correlate in vivo MRI findings with ex vivo immunohistological analysis.
• To assess the presence of lesions irrespective of clinical symptom development.

Main Methods:

• Induction of EAE in SJL/J mice via proteolipid protein-specific T-cell transfer.
• Longitudinal high-field-strength MRI with contrast agents (gadopentetate dimeglumine) to assess blood-brain barrier (BBB) disruption.
• Visualization of inflammatory nerve injury using gadofluorine M and phagocytic cells using VSOP-C184.
• Correlation of MRI data with immunohistological examination of brain and spinal cord tissues.

Main Results:

• Early blood-brain barrier breakdown was detected in both white and grey matter in 25 out of 26 mice.
• Disseminated contrast-enhancing lesions, preceding clinical onset, were observed in 10 mice.
• Lesions were present in four mice without any clinical signs of disease.
• Cranial nerves, including optic and trigeminal nerves, showed MRI signal changes in 14 mice.
• Histological analysis confirmed cellular infiltrates at all MRI-identified lesion sites.

Conclusions:

• Early and widespread dissemination of inflammatory lesions, including cranial nerves, occurs in EAE prior to or at the earliest stages of clinical disease.
• The observed discrepancy between MRI-detected disease burden and clinical disability mirrors the human clinico-radiological paradox in MS.
• MRI should be integrated into routine evaluations of therapeutic efficacy in future EAE studies.