title: Experimental models of neuroprotection relevant to multiple sclerosis.
abstract: Activated T cells, particularly those of the T-helper (Th) 1 subset, have the capacity to kill neurons. Strategies for preventing such damage may include deviation of activated T cells into the Th2 subset (e.g., via use of glatiramer acetate), alteration of functional properties of Th1 cells (e.g., through use of interferon [INF]-beta or IV immunoglobulin), and inhibition of activated cell migration into the CNS (e.g., by employing INF-beta or natalizumab). Matrix metalloproteinase-9 (MMP-9) also causes neuron death in neurotoxicity models, and examination of medications with MMP inhibitory activity indicates that minocycline is capable of preventing such damage. Minocycline also has other properties relevant to conferring neuroprotection, such as inhibition of microglial activity and apoptosis pathways. In a small pilot study in patients with relapsing-remitting multiple sclerosis, minocycline treatment produced favorable outcomes in terms of gadolinium-enhancing lesions and clinical course. Further studies are needed to establish whether experimental neuroprotection strategies involving these mechanisms may be translated into preventing neurodegeneration in multiple sclerosis.
authors.affiliation: Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Alberta, Canada. vyong@ucalgary.ca
authors.forename: V W
authors.initials: VW
authors.lastname: Yong
authors.forename: F
authors.initials: F
authors.lastname: Giuliani
authors.forename: M
authors.initials: M
authors.lastname: Xue
authors.forename: A
authors.initials: A
authors.lastname: Bar-Or
authors.forename: L M
authors.initials: LM
authors.lastname: Metz
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents