Department of Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany.
PLoS One. 2012;7(9):e42597. doi: 10.1371/journal.pone.0042597. Epub 2012 Sep 25.
To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).
70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry.
DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only), as compared to the sham operated group (p<0.001). Only animals within group 3 and the highest nimodipine microparticles concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury.
Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.
研究局部应用尼莫地平缓释微球对实验性蛛网膜下腔出血（SAH）后血管痉挛和继发性脑损伤的影响。
70 只雄性 Wistar 大鼠分为三组：1）假手术组（对照组）、2）单纯 SAH 组（对照组）和 3）治疗组。采用双出血模型诱导 SAH。治疗组给予不同浓度（20%、30%或 40%）的尼莫地平微球。5 天后采用数字减影血管造影（DSA）评估血管造影性血管痉挛。通过 H&E 染色以及 Iba1 和 MAP2 免疫组化对冷冻切片进行组织学分析。
42 只动物的 DSA 图像足以进行评估。与假手术组相比，单纯 SAH 组（仅 SAH 组）存在严重的血管造影性血管痉挛（p<0.001）。只有治疗组 3 组和尼莫地平微球浓度最高（40%）以及假手术组 1 组（假手术组）的动物显示出最大的颅内动脉直径。然而，血管口径的变化并未导致 Iba-1 或 MAP2 表达的差异，即继发性脑损伤的组织学发现。
局部给予高浓度大剂量尼莫地平缓释微球可显著减少实验性 SAH 后的血管造影性血管痉挛，且无基质毒性的组织学迹象。
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