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CNS-targeted glucocorticoid reduces pathology in mouse model of amyotrophic lateral sclerosis

Evans, M C; Gaillard, P J; De Boer, M; Appeldoorn, C; Dorland, R; Sibson, N R; Turner, M R; Anthony, D C; Stolp, H B

Authors

M C Evans

P J Gaillard

M De Boer

C Appeldoorn

R Dorland

N R Sibson

M R Turner

D C Anthony

H B Stolp



Abstract

Hallmarks of CNS inflammation, including microglial and astrocyte activation, are prominent features in post-mortem tissue from amyotrophic lateral sclerosis (ALS) patients and in mice overexpressing mutant superoxide dismutase-1 (SOD1 G93A ). Administration of non-targeted glucocorticoids does not significantly alter disease progression, but this may reflect poor CNS delivery. Here, we sought to discover whether CNS-targeted, liposomal encapsulated glucocorticoid would inhibit the CNS inflammatory response and reduce motor neuron loss. SOD1 G93A mice were treated with saline, free methylprednisolone (MP, 10 mg/kg/week) or glutathione PEGylated liposomal MP (2B3-201, 10 mg/kg/week) and compared to saline treated wild-type animals. Animals were treated weekly with intravenous injections for 9 weeks from 60 days of age. Weights and motor performance were monitored during this period. At the end of the experimental period (116 days) mice were imaged using T 2-weighted MRI for brainstem pathology; brain and spinal cord tissue were then collected for histological analysis.

Citation

Evans, M. C., Gaillard, P. J., De Boer, M., Appeldoorn, C., Dorland, R., Sibson, N. R., …Stolp, H. B. (2014). CNS-targeted glucocorticoid reduces pathology in mouse model of amyotrophic lateral sclerosis. Acta Neuropathologica Communications, 2, 66. https://doi.org/10.1186/2051-5960-2-66

Journal Article Type Article
Acceptance Date Jun 2, 2014
Publication Date Jun 13, 2014
Deposit Date Jul 13, 2018
Publicly Available Date Aug 31, 2018
Journal Acta Neuropathologica Communications
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 2
Pages 66
DOI https://doi.org/10.1186/2051-5960-2-66
Public URL https://rvc-repository.worktribe.com/output/1405480

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