PDCB does not promote CNS autoimmunity in the context of genetic susceptibility but worsens its outcome

Dubey, Divyanshu; Hussain, Rehana Z.; Miller-Little, William A.; Salter, Amber; Doelger, Richard; Stüve, Olaf

doi:10.1016/j.jneuroim.2018.07.012

Cited by 1 publication

(1 citation statement)

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“…It has been previously reported that 2D2 + mice develop spontaneous EAE with low incidence (0 to 20%) when housed under SPF conditions (16,(23)(24)(25)(26). We observed EAE incidence to be higher in our 2D2 + colony, with ∼25% of mice developing classic EAE signs including tail and hind-limb paralysis (Table 1).…”

Section: Resultssupporting

confidence: 61%

Aged hind-limb clasping experimental autoimmune encephalomyelitis models aspects of the neurodegenerative process seen in multiple sclerosis

Cahill

Zhang

Ramaglia

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Experimental autoimmune encephalomyelitis (EAE) is the most common model of multiple sclerosis (MS). This model has been instrumental in understanding the events that lead to the initiation of central nervous system (CNS) autoimmunity. Though EAE has been an effective screening tool for identifying novel therapies for relapsing-remitting MS, it has proven to be less successful in identifying therapies for progressive forms of this disease. Though axon injury occurs in EAE, it is rapid and acute, making it difficult to intervene for the purpose of evaluating neuroprotective therapies. Here, we describe a variant of spontaneous EAE in the 2D2 T cell receptor transgenic mouse (2D2+ mouse) that presents with hind-limb clasping upon tail suspension and is associated with T cell-mediated inflammation in the posterior spinal cord and spinal nerve roots. Due to the mild nature of clinical signs in this model, we were able to maintain cohorts of mice into middle age. Over 9 mo, these mice exhibited a relapsing-remitting course of hind-limb clasping with the development of progressive motor deficits. Using a combined approach of ex vivo magnetic resonance (MR) imaging and histopathological analysis, we observed neurological progression to associate with spinal cord atrophy, synapse degradation, and neuron loss in the gray matter, as well as ongoing axon injury in the white matter of the spinal cord. These findings suggest that mild EAE coupled with natural aging may be a solution to better modeling the neurodegenerative processes seen in MS.

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