Thalamus Degeneration and Inflammation in Two Distinct Multiple Sclerosis Animal Models.

There is a broad consensus that multiple sclerosis (MS) represents more than an inflammatory disease: it harbors several characteristic aspects of a classical neurodegenerative disorder, i.e., damage to axons, synapses, and nerve cell bodies. While several accepted paraclinical methods exist to monitor the inflammatory-driven aspects of the disease, techniques to monitor progression of early and late neurodegeneration are still in their infancy and have not been convincingly validated. It was speculated that the thalamus with its multiple reciprocal connections is sensitive to inflammatory processes occurring in different brain regions, thus acting as a "barometer" for diffuse brain parenchymal damage in MS. To what extent the thalamus is affected in commonly applied MS animal models is, however, not known. In this article we describe direct and indirect damage to the thalamus in two distinct MS animal models. In the cuprizone model, we observed primary oligodendrocyte stress which is followed by demyelination, microglia/astrocyte activation, and acute axonal damage. These degenerative cuprizone-induced lesions were found to be more severe in the lateral compared to the medial part of the thalamus. In MOG35-55-induced EAE, in contrast, most parts of the forebrain, including the thalamus were not directly involved in the autoimmune attack. However, important thalamic afferent fiber tracts, such as the spinothalamic tract were inflamed and demyelinated on the spinal cord level. Quantitative immunohistochemistry revealed that this spinal cord inflammatory-demyelination is associated with neuronal loss within the target region of the spinothalamic tract, namely the sensory ventral posterolateral nucleus of the thalamus. This study highlights the possibility of trans-neuronal degeneration as one mechanism of secondary neuronal damage in MS. Further studies are now warranted to investigate involved cell types and cellular mechanisms.