Contributions
Abstract: P1015
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 19 Neurodegeneration
Background and purpose: 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 subcortex with its multiple reciprocal connections is sensitive to neurodegenerative events occurring in different brain regions, thus acting as a 'barometer' for diffuse brain parenchymal damage in MS. Here we compare the extent of cortical versus subcortical brain atrophy in the cuprizone model.
Materials and methods: Male C57BL/6J mice were fed cuprizone (0.25%) for five and twelve weeks. Immunohistochemistry was performed to detect demyelination and innate immune activation. To measure brain atrophy, a systematically and randomly sampled series of ten 40 µm thick cryosections was prepared and stained with cresyl violet. The Cavalieri principle, a design-based stereologic method, was used to estimate the cortical and subcortical volumes.
Results: After 5 weeks cuprizone treatment there was diffuse demyelination, paralleled by acute axonal injury, reactive astrocytosis and microglia activation. At this early time point, cortical as well as subcortical volumes were unchanged. After 12 weeks, stereological evaluation revealed a significant volume loss of the subcortex, whereas volume of the cortex was unchanged.
Conclusion: These results are in line with a specific subcortical grey-matter atrophy found in MS patients, and 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. We propose that evaluation of subcortical brain volume in the chronic cuprizone model serves as a valuable tool to study neuroprotection in MS, especially in the context of progressive disease.
Disclosure:
Kai Fabisch: nothing to disclose
Caroline Roggenkamp: nothing to disclose
Kerstin Hecher: nothing to disclose
Markus Kipp: nothing to disclose
Tanja Hochstrasser: nothing to disclose
Abstract: P1015
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 19 Neurodegeneration
Background and purpose: 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 subcortex with its multiple reciprocal connections is sensitive to neurodegenerative events occurring in different brain regions, thus acting as a 'barometer' for diffuse brain parenchymal damage in MS. Here we compare the extent of cortical versus subcortical brain atrophy in the cuprizone model.
Materials and methods: Male C57BL/6J mice were fed cuprizone (0.25%) for five and twelve weeks. Immunohistochemistry was performed to detect demyelination and innate immune activation. To measure brain atrophy, a systematically and randomly sampled series of ten 40 µm thick cryosections was prepared and stained with cresyl violet. The Cavalieri principle, a design-based stereologic method, was used to estimate the cortical and subcortical volumes.
Results: After 5 weeks cuprizone treatment there was diffuse demyelination, paralleled by acute axonal injury, reactive astrocytosis and microglia activation. At this early time point, cortical as well as subcortical volumes were unchanged. After 12 weeks, stereological evaluation revealed a significant volume loss of the subcortex, whereas volume of the cortex was unchanged.
Conclusion: These results are in line with a specific subcortical grey-matter atrophy found in MS patients, and 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. We propose that evaluation of subcortical brain volume in the chronic cuprizone model serves as a valuable tool to study neuroprotection in MS, especially in the context of progressive disease.
Disclosure:
Kai Fabisch: nothing to disclose
Caroline Roggenkamp: nothing to disclose
Kerstin Hecher: nothing to disclose
Markus Kipp: nothing to disclose
Tanja Hochstrasser: nothing to disclose