Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination.
A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved. Therefore, therapeutic agents that protect the CNS are warranted. In both animal models as well as human patients with MS, T cell entry into the CNS is generally considered the initiating inflammatory event. In order to assess if a drug protects the CNS, any potential effects on immune cell infiltration or proliferation in the periphery must be ruled out. This protocol describes how to determine whether CNS protection observed after drug intervention is a consequence of attenuating CNS-infiltrating immune cells or blocking death of CNS cells during inflammatory insults. The ability to examine MS treatments that are protective to the CNS during inflammatory insults is highly critical for the advancement of therapeutic strategies since current treatments reduce, but do not completely eliminate, relapses (i.e., immune cell infiltration), leaving the CNS vulnerable to degeneration.
Physical Medicine and Rehabilitation, University of Alabama at Birmingham.
Kirsten S
KS
Evonuk
Department of Pathology, University of Alabama at Birmingham.
Carson E
CE
Moseley
Physical Medicine and Rehabilitation, University of Alabama at Birmingham.
Ryan E
RE
Doyle
Department of Pathology, University of Alabama at Birmingham.
Casey T
CT
Weaver
Physical Medicine and Rehabilitation, University of Alabama at Birmingham; Department of Neurobiology, University of Alabama at Birmingham; Center for Glial Biology and Medicine, University of Alabama at Birmingham; desilvt@ccf.org.
Tara M
TM
DeSilva
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D007107:Immune System / Q000187:drug effects; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents
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