Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

Evonuk, Kirsten S.; Moseley, Carson E.; Doyle, Ryan E.; Weaver, Casey T.; DeSilva, Tara M.

Further confirmation for neuroprotection can be accomplished using a co-culture system 11 to test specific mechanisms of cell death or through the use of conditional knockout mice which allows for deletion of proteins selectively on a cell type. Furthermore, to extend the exploration of pharmacological agents that are neuroprotective, markers of axonal transection and neuronal death should be included. Another area of importance is remyelination. Injured axons are unable to remyelinate lending further support that neuroprotective therapies should be an important part of remyelination therapies. Additionally, unmyelinated axons are more vulnerable to injury than myelinated axons. This suggests that when an axon becomes demyelinated therapeutic interventions that promote timely remyelination will prevent axonal injury. To explore these avenues, other in vivo models for demyelination and remyelination may be used (i.e., cuprizone and lysolecithin). The method described herein focused on assessing neuroprotection by quantifying myelin loss. For the evaluation of remyelination the number of progenitor cells as well as their ability to proliferate and mature would also be important to investigate. With the mention of these alternative models, one must also consider different models of encephalitis that are virally mediated. There are two well-characterized RNA viral models that produce myelin loss: one is Theiler's murine encephalomyelitis, a non-enveloped Picornaviridae virus, and the other is mouse hepatitis virus, a member of the Coronaviridae virus family 25, 26 .