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

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: Nov 21, 2020
• 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