What’s Street light science?
Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis. Hamilton AM, Forkert ND, Yang R, Wu Y, Rogers JA, Yong VW, Dunn JF. Sci Rep. 2019; 9(1):8488. doi: 10.1038/s41598-019-44682-6
Atrophy has become a clinically relevant marker of progressive neurodegeneration in multiple sclerosis (MS). To better understand atrophy, mouse models that feature atrophy along with other aspects of MS are needed. The experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to determine the extent of atrophy in a model of inflammation-associated central nervous system pathology. High-resolution magnetic resonance imaging (MRI) and atlas-based volumetric analysis were performed to measure brain regional volumes in EAE mice. EAE brains were larger at peak clinical disease (days 14-16) compared to controls, with affected regions including the cerebellum, hippocampus, and corpus callosum. Following peak clinical disease, EAE mice exhibited significant loss of volume at chronic long-term disease duration (day 66+). Atrophy was identified in both white and grey matter regions including the cerebral cortex, cerebellum, hippocampus, corpus callosum, basal forebrain, midbrain, optic tract, and colliculus. Histological analysis of the atrophied cortex, cerebellum, and hippocampus showed demyelination, and axonal/neuronal loss. We hypothesize this atrophy could be a result of inflammatory associated neurodegenerative processes, which may also be involved in MS. Using MRI and atlas-based volumetrics, EAE has the potential to be a test bed for treatments aimed at reducing progressive neurological deterioration in MS
EAE in rodents is largely a spinal cord disease and many areas of the brain are not directly lesioned including many of the areas examined in this study. That the brain is shrinking can mean it is directly being targeted but because of marked nerve loss in the spinal cord. Many innervation pathways leading to the brain are lost, so is this why the nerves go?…But then we have suggestion here that this reflects the events in progressive disability. We have had a suggestion of a new lesion type with cortical degeneration at the core. I suspect this can be explained by mouse EAE.
I also suspect that this degeneration is largely be a consequence of effects on relapsing disease, which is suggested, but this is not what we need for progressive MS.
Now the street light effect
It’s doing the easy thing when the correct thing (spinal cord imaging) is harder