Calcium channel blockers ameliorate disease in a mouse model of multiple sclerosis.
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, are inflammatory demyelinating diseases of the central nervous system. The inflammatory attacks lead to glial dysfunction and death, axonal damage, and neurological deficits. Numerous studies in rat suggest that extracellular calcium influx, via voltage-gated calcium channels (VGCC), contributes to white matter damage in acute spinal cord injury and stroke. Our immunohistochemical finding that mouse spinal cord axons display subunits of L-type VGCC also supports this hypothesis. Furthermore, we hypothesized that VGCC also play a role in EAE, and possibly, MS. In our study, administration of the calcium channel blockers (CCB) bepridil and nitrendipine significantly ameliorated EAE in mice, compared with vehicle-treated controls. Spinal cord samples showed reduced inflammation and axonal pathology in bepridil-treated animals. Our data support the hypothesis that calcium influx via VGCC plays a significant role in the development of neurological disability and white matter damage in EAE and MS.
Brand-Schieber
Elimor
E
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Werner
Peter
P
D000818:Animals; D001369:Axons / Q000378:metabolism; D015764:Bepridil / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009568:Nitrendipine / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000209:etiology
C485995:Cacna1d protein, mouse; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004676:Myelin Basic Protein; D015764:Bepridil; D009568:Nitrendipine