Kupsch A, Gerlach M, Pupeter S C, Sautter J, Dirr A, Arnold G, Opitz W, Przuntek H, Riederer P, Oertel W H
Klinikum Grosshadern, Department of Neurology, Ludwig-Maximilians-University, München, Germany.
Neuroreport. 1995 Mar 7;6(4):621-5. doi: 10.1097/00001756-199503000-00009.
The present study assessed the effects of pretreatment with the calcium-L-type channel blocker nimodipine on biochemical and histological parameters of systemic MPTP-induced (2 x 40 mg kg-1 body weight subcutaneously, 16 h apart), dopaminergic neurotoxicity in black C57BL/6 mice. Continuous administration of nimodipine via subcutaneously implanted pellets (10 mg), starting 7 days before administration of MPTP, did not antagonize the striatal MPTP-induced dopamine depletion (caudate-putamen: 80% of control; nucleus accumbens; 25% of control), but almost completely prevented the MPTP-induced tyrosine hydroxylase immunoreactive-cell loss in the substantia nigra (20% of control) 7 days after administration of MPTP. This data suggests that pretreatment with nimodipine--during the observation period of 7 days--protects against MPTP-induced neurotoxicity in mice at the nigral ('cell body'), but not at the synaptic striatal level.
本研究评估了用L型钙通道阻滞剂尼莫地平预处理对系统性给予MPTP（2×40mg/kg体重，皮下注射，间隔16小时）诱导的黑C57BL/6小鼠多巴胺能神经毒性的生化和组织学参数的影响。在给予MPTP前7天开始，通过皮下植入药丸（10mg）持续给予尼莫地平，并未拮抗MPTP诱导的纹状体多巴胺耗竭（尾状核-壳核：对照组的80%；伏隔核：对照组的25%），但在给予MPTP 7天后，几乎完全防止了MPTP诱导的黑质中酪氨酸羟化酶免疫反应性细胞损失（对照组的20%）。该数据表明，在7天的观察期内用尼莫地平预处理可保护小鼠免受MPTP诱导的黑质（“细胞体”）神经毒性，但不能保护突触纹状体水平。
