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Correlation between MRI and clinico-pathological manifestations in Lewis rats protected from experimental allergic
S J Karlik1, D Munoz, J St Louis
1Department of Diagnostic Radiology, The John P. Robarts Research Institute, The University of Western Ontario, London, Canada. skarlik@irus.rri.on.ca
Abstract:
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system which constitutes an accepted animal model for multiple sclerosis (MS). The disease can take an acute or chronic form depending on the injection route, animal strain and nature of the disease-inducing antigen administered. The neuroinflammation associated with the acute form can be detected with T2-weighted, T1-weighted and diffusion MRI, and blood-brain barrier changes can be investigated with Gd-DTPA-enhanced T1-weighted imaging, similar to that of MS patients. A synthetic peptide of myelin basic protein (MBP) encephalitogenic for the Lewis rat (MBP 68-86) was acylated by the attachment of a palmitoyl residue (PAL68-86), and was shown to confer almost complete protection against EAE, when administered to rats before and after an encephalitogenic challenge. In this study, treatment of Lewis rats with PAL68-86 prevented the appearance of clinical signs (p < 0.0001) after challenge with the native peptide (p68-86) in complete Freund's adjuvant (CFA), and reduced considerably the MRI and histopathological signs of the disease (p < 0.0001). Measurement of the gadolinium leakage due to neuroinflammation revealed a significant decrease in permeability from 4.09 +/- 2.1 to 2.95 +/- 1.79% pixels > mean + 2 SD (p = 0.011). Therefore, quantitative MRI measurements correlate very well with the reduced cellular infiltration in the CNS and the absence of clinical signs in the EAE-protected animal.
Insights
PAL68-86 treatment significantly protected Lewis rats against experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis (MS). This protection was confirmed by reduced clinical signs, MRI evidence of neuroinflammation, and decreased blood-brain barrier permeability.
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
- Animal Models of Neurological Disorders
Background:
- Experimental allergic encephalomyelitis (EAE) is a key animal model for studying multiple sclerosis (MS).
- Neuroinflammation and blood-brain barrier (BBB) disruption are hallmarks of EAE and MS.
- Previous studies indicated that a modified myelin basic protein peptide (PAL68-86) offers protection against EAE.
Purpose of the Study:
- To evaluate the therapeutic efficacy of PAL68-86 in preventing and reducing EAE.
- To correlate clinical outcomes with Magnetic Resonance Imaging (MRI) and histopathological findings.
- To assess the impact of PAL68-86 on BBB integrity in EAE.
Main Methods:
- Lewis rats were treated with PAL68-86 before and after challenge with the encephalitogenic peptide (MBP 68-86) in complete Freund's adjuvant (CFA).
- Clinical signs of EAE were monitored daily.
- Neuroinflammation and BBB permeability were assessed using T2-weighted, T1-weighted, and Gd-DTPA-enhanced MRI.
- Histopathological analysis was performed to evaluate cellular infiltration in the central nervous system (CNS).
Main Results:
- PAL68-86 treatment significantly prevented clinical EAE development (p < 0.0001).
- MRI and histopathology showed considerable reduction in disease signs and CNS cellular infiltration (p < 0.0001).
- Gd-DTPA leakage, indicating BBB permeability, decreased significantly from 4.09% to 2.95% (p = 0.011).
Conclusions:
- PAL68-86 is a potent therapeutic agent for EAE, effectively reducing clinical and pathological manifestations.
- Quantitative MRI parameters, including BBB permeability, correlate well with reduced neuroinflammation and clinical protection.
- This study reinforces the utility of PAL68-86 as a potential therapeutic strategy for MS.
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