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Influence of methylprednisolone on magnetic resonance and histological measures during cuprizone-induced
Holly S Cate1, Qi-Zhu Wu, Dennis Kemper
1Howard Florey Institute, University of Melbourne, Victoria, Australia. hcate@unimelb.edu.au
Abstract:
MRI is widely used for routine assessment of the progression of white matter injury while patients receive therapeutic agents, such as the glucocorticoid agonist methylprednisolone (MP). Given this, it is important to determine whether MRI parameters are altered by MP treatment in the absence of changes in cellular and myelin pathology. In this study, we compared magnetic resonance and histological measures during myelin injury in mice with and without short duration MP administration. Mice were scanned with a 4.7T MRI scanner before and after MP or vehicle injections using T2WI and DTI sequences and histology was performed on the brains following the second scan. Comparison of post-injection to pre-injection MRI showed a reduced T2WI intensity in the CC and an attenuated response in ADC|| and ADC perpendicular in the MP group in comparison with the vehicle group. However, quantitative analyses of myelin staining, neurofilament intensity and oligodendrocyte and microglial density were not different between the MP and the vehicle groups, indicating that the short duration MP treatment did not alter cellular and myelin pathology. These data suggest that MP could confound the validity of paraclinical measures such as ADC|| and ADC perpendicular that are otherwise being touted as markers of either axonal integrity or myelin repair.
Insights
Short-term methylprednisolone (MP) treatment altered MRI parameters like T2WI and ADC in mice with white matter injury. However, it did not affect cellular or myelin pathology, suggesting MP may confound MRI-based assessments.
Area of Science:
- Neuroimaging
- Neuropathology
- Pharmacology
Background:
- Magnetic Resonance Imaging (MRI) is crucial for monitoring white matter injury progression during therapeutic interventions.
- Glucocorticoid agonists, like methylprednisolone (MP), are commonly used in treating such conditions.
- It is essential to understand if MP influences MRI parameters independently of underlying tissue pathology.
Purpose of the Study:
- To investigate the effects of short-duration methylprednisolone (MP) administration on MRI parameters in the context of white matter injury.
- To compare MRI findings with histological assessments of myelin and cellular pathology.
- To determine if MP treatment confounds MRI-based markers of axonal integrity or myelin repair.
Main Methods:
- Comparison of MRI (T2WI, DTI) and histological measures in mice with induced white matter injury.
- Mice received either MP or vehicle injections, with MRI scans performed before and after treatment.
- Histological analysis focused on myelin staining, neurofilament intensity, and glial cell density.
Main Results:
- MP treatment led to reduced T2WI intensity in the corpus callosum (CC) and attenuated changes in ADC|| and ADC perpendicular compared to vehicle.
- Histological analyses revealed no significant differences in myelin staining, neurofilament intensity, or oligodendrocyte/microglial density between groups.
- These findings indicate that MP altered MRI signals without affecting cellular or myelin pathology.
Conclusions:
- Short-term methylprednisolone administration can alter specific MRI parameters (T2WI, ADC) in white matter injury models.
- These alterations occur independently of changes in myelin or cellular pathology.
- The study suggests that MP may confound the interpretation of ADC measures as markers of axonal integrity or myelin repair.
