Background Cerebral stroke occurs following ischemic and hemorrhagic lesions in the brain. Survival and recovery of stroke patients depend on the severity of the initial injury but also the therapeutic approaches applied for emergent lifesaving and continuing post-stroke management. Dl-3-n-Butylphthalide (NBP), an active compound derived from Chinese celery seeds, has shown clinical efficacy in the treatment of ischemic cerebral stroke. Results In the present study we explored the therapeutic effect of NBP in a rat model of intracerebral hemorrhage (ICH), focusing on its potential role in promoting neovascularization in the perihemorrhagic zone. ICH was induced in male Sprague-Dawley rats by unilateral injection of autologous blood into the globus pallidus, with sham-operated (Sham group), vehicle-treated (ICH) and NBP-treated (at 10 and 25 mg/kg/Bid, p.o., ICH + NBP10 and ICH + NBP25, respectively) groups examined behaviorally, macroscopically, histologically and biochemically at 1, 3, 7 and 15 days (d) post operation. Rats in the ICH + NBP10 and ICH + NBP25 groups showed reduced Longa’s motor scores relative to the ICH groups at the 3 and 7d time points, while the hematoma volume was comparable in the two NBP relative to the ICH groups as measured at 7d and 15d. In the perihemorrhagic zone, the numeric density of blood vessels immunolabeled by CD34, an angiogenic marker, was greater in the ICH + NBP10 and ICH + NBP25 than ICH groups, more so in the higher dosage group, at 1, 3, 7 and 15d. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins-2 (Ang-2) proteins were elevated in the NBP groups relative to the sham and vehicle controls in immunoblotting of tissue lysates from the injection region. Conclusion These results suggest that NBP can alleviate neurological defects following experimentally induced local brain hemorrhage, which is associated with a potential role of this drug in promoting neovascularization surrounding the bleeding loci.

中文翻译：

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Dl-3-n-Butylphthalide 促进脑出血大鼠模型的新生血管形成和神经功能恢复

背景 脑中风发生在大脑缺血性和出血性病变之后。中风患者的生存和恢复取决于初始损伤的严重程度，也取决于用于紧急救生和持续中风后管理的治疗方法。Dl-3-n-Butylphthalide (NBP) 是一种源自芹菜籽的活性化合物，已显示出治疗缺血性脑卒中的临床疗效。结果在本研究中，我们探讨了 NBP 在脑出血 (ICH) 大鼠模型中的治疗效果，重点是其在促进出血周围区新血管形成方面的潜在作用。在雄性 Sprague-Dawley 大鼠中通过单侧向苍白球注射自体血诱导 ICH，假手术（假手术组），在 1、3、7 和 15 时对经载体处理 (ICH) 和 NBP 处理（分别为 10 和 25 mg/kg/Bid、po、ICH + NBP10 和 ICH + NBP25）的组进行行为、宏观、组织学和生化检查术后天数 (d)。在第 3 天和第 7 天，ICH + NBP10 和 ICH + NBP25 组中的大鼠表现出相对于 ICH 组的 Longa 运动评分降低，而在第 7 天和第 15 天测量的两个 NBP 相对于 ICH 组的血肿体积相当. 在出血周围区域，血管生成标志物 CD34 免疫标记的血管数量密度在 ICH + NBP10 和 ICH + NBP25 组中高于 ICH 组，在高剂量组中更是如此，在 1、3、7 和 15 d . 在注射区域的组织裂解物的免疫印迹中，相对于假手术和载体对照，NBP 组中血管内皮生长因子 (VEGF) 和血管生成素-2 (Ang-2) 蛋白的水平升高。结论 这些结果表明，NBP 可以减轻实验诱导的局部脑出血后的神经缺陷，这与该药物在促进出血位点周围新血管形成方面的潜在作用有关。