Chandra S, White R F, Everding D, Feuerstein G Z, Coatney R W, Sarkar S K, Barone F C
Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa., USA.
Pharmacology. 1999 Jun;58(6):292-9. doi: 10.1159/000028294.
The neuroprotective effects of isradipine, a 2,4-dihydropyridine calcium channel blocker, has been well studied in the rat model of focal ischemia (induced by middle cerebral artery occlusion, MCAO). The present study was designed to evaluate whether isradipine pretreatment caused early (0-3 h after stroke) ischemic changes in diffusion- weighted magnetic resonance imaging (DWI) and if such changes were predictive of previously documented protection in brain infarction. An initial dose-response study using neurological deficit scores and estimates of protection from brain infarction (by histology) showed that isradipine reduced cortical infarctions compared to vehicle-treated animals at most doses (between 1.25 and 5 mg/kg/day s.c. for 6 days) with the best results obtained at 5 mg/kg/day, where a 78.5% reduction was observed. This dose was utilized to perform the DWI study. Early quantitative estimates of infarct size, as measured by DWI at 1, 2 and 3 h after MCAO, were similar to those obtained with late histology at 24 h. These data indicate that in pretreatment protocols, DWI can be used to quantitatively predict areas at risk of permanent damage. This work also demonstrates that neurological deficits, developing from the damaged forebrain following focal stroke, may provide an index of isradipine's neuroprotective activity.
2,4-二氢吡啶类钙通道阻滞剂伊拉地平的神经保护作用已在局灶性缺血大鼠模型（由大脑中动脉闭塞，即MCAO诱导）中得到充分研究。本研究旨在评估伊拉地平预处理是否会在扩散加权磁共振成像（DWI）中引起早期（中风后0 - 3小时）缺血性变化，以及这些变化是否能预测先前记录的脑梗死保护作用。一项使用神经功能缺损评分和脑梗死保护评估（通过组织学）的初始剂量反应研究表明，与赋形剂处理的动物相比，伊拉地平在大多数剂量（1.25至5毫克/千克/天皮下注射，共6天）下均可减少皮质梗死，在5毫克/千克/天的剂量下效果最佳，观察到梗死减少了78.5%。该剂量用于进行DWI研究。在MCAO后1、2和3小时通过DWI测量的梗死大小的早期定量估计与24小时后期组织学获得的结果相似。这些数据表明，在预处理方案中，DWI可用于定量预测有永久性损伤风险的区域。这项工作还表明，局灶性中风后受损前脑出现的神经功能缺损可能提供伊拉地平神经保护活性的指标。
