Influence of methylprednisolone on magnetic resonance and histological measures during cuprizone-induced demyelination.
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.
Cate
Holly S
HS
Howard Florey Institute, University of Melbourne, Victoria, Australia. hcate@unimelb.edu.au
Wu
Qi-Zhu
QZ
Kemper
Dennis
D
Merlo
Daniel
D
Wang
Hong-Xin
HX
Fang
Ke
K
Egan
Gary F
GF
Kilpatrick
Trevor J
TJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003471:Cuprizone / Q000494:pharmacology*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology
D005938:Glucocorticoids; D003471:Cuprizone; D008775:Methylprednisolone