Premium
Ca 2+ blockers ameliorate disease in mouse model of multiple sclerosis (MS)
Author(s) -
BrandSchieber E.,
Werner P.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.16_6.x
Subject(s) - adoptive cell transfer , multiple sclerosis , experimental autoimmune encephalomyelitis , white matter , immune system , medicine , immunology , pharmacology , endocrinology , t cell , magnetic resonance imaging , radiology
Influx of extracellular Ca 2+ is implicated in CNS white matter injury. We studied the effects of clinically used Ca 2+ blockers on mouse adoptive‐transfer EAE (AT‐EAE), a model of MS, an inflammatory white matter disease. Lymph node cells (LNC) from donor mice, sensitized to a CNS antigen, MBP, and clonally expanded in vitro with the same antigen, were injected I.V. to recipient SJL/J mice. Mouse AT‐EAE presents an initial acute ascending paralysis (onset 8–10 days, remission 18–20 days after LNC transfer) and a relapsing–remitting disease course thereafter. Bepridil (BEP), a Ca 2+ blocker (3 mg/kg/day), reduced average clinical score of AT‐EAE by 1.5–2 points (out of 5; p < 0.05) compared with vehicle control (VEH), when treatment started on day 0, as well as, on day 3 post‐LNC transfer. Nitrendipine, a selective voltage‐gated Ca 2+ ‐channel blocker (2.5 mg/kg/day), started on day 0, ameliorated AT‐EAE ( p < 0.05) compared with VEH, in a manner similar to BEP. That two different calcium antagonists provided similar benefits points at a common target, likely voltage gated Ca 2+ channels. As to mechanism, BEP reduced white matter pathology but not peripheral monocyte infiltration, assessed by histochemistry, suggesting that BEP may have suppressed secondary damage that followed the initial immune attack. However, we can not rule out an effect of BEP on immune cell competence since LNC, treated with BEP before transfer to recipient mice, only induced a much delayed and weaker EAE compared with vehicle treated cells. Moreover, besides attenuating the acute phase of AT‐EAE, long‐term BEP treatment seems to decrease the number of relapses. Our data implicates Ca 2+ influx in AT‐EAE and suggest Ca 2+ blockers as potential therapeutics in MS.