  Multiple sclerosis is a neurological disorder in which the myelin sheaths of
axons are damaged by the immune response. We report here a three-dimensional
structural analysis of brain and spinal cord tissues of a mouse model of
multiple sclerosis, known as experimental autoimmune encephalomyelitis (EAE).
EAE-induced mice were raised with or without administration of fingolimod,
which is used in the treatment of multiple sclerosis. Brains and spinal cords
dissected from the EAE mice were lyophilized so as to reconstitute the
intrinsic contrast of tissue elements, such as axons, in X-ray images.
Three-dimensional structures of the brain hemispheres and spinal cords of the
EAE mice were visualized with synchrotron radiation microtomography.
Microtomographic cross sections reconstructed from the X-ray images revealed
dilation of capillary vessels and vacuolation in the spinal cord of the EAE
mice. Vacuolation was also observed in the cerebellum, suggesting that the
neuroinflammatory response progressed in the brain. The vessel networks and
vacuolation lesions in the spinal cords were modelled by automatically tracing
the three-dimensional image in order to analyze the tissue structures
quantitatively. The results of the analysis indicated that the distribution of
vacuolations was not uniform but three-dimensionally localized. The mean vessel
diameter showed a linear correlation with the clinical score, indicating that
vasodilation is relevant to paralysis severity in the disease model. We suggest
that vasodilation and vacuolation are related with neurological symptoms of
multiple sclerosis.
