Here we examined the effect of nicotine on angiogenesis in the brain after intracerebral hemorrhage (ICH), as angiogenesis is considered to provide beneficial effects on brain tissues during recovery from injury after stroke. Nicotine was administered to C57BL/6 mice suffering from collagenase-induced ICH in the striatum, either by inclusion in drinking water or by daily intraperitoneal injection. Nicotine administration by both routes enhanced angiogenesis within the hematoma-affected regions, as revealed by increased CD31-immunopositive area at 7 and 14 d after ICH. Double immunofluorescence histochemistry against CD31 and proliferating cell nuclear antigen revealed that nicotine increased the number of newly generated vascular endothelial cells within the hematoma. In spite of enhanced angiogenesis, nicotine did not worsen vascular permeability after ICH, as assessed by Evans Blue extravasation. These effects of nicotine were accompanied by an increased number of surviving neurons in the hematoma at 7 d after ICH. Unexpectedly, nicotine did not increase expression of vascular endothelial growth factor mRNA in the brain and did not enhance recruitment of endothelial progenitor cells from the bone marrow. These results suggest that nicotine enhances angiogenesis in the brain after ICH, via mechanisms distinct from those involved in its action on angiogenesis in peripheral tissues.

在这里，我们检查了尼古丁对脑内出血 (ICH) 后脑血管生成的影响，因为血管生成被认为在中风后损伤恢复期间对脑组织提供有益影响。通过将尼古丁包含在饮用水中或每天腹膜内注射，向患有纹状体中胶原酶诱导的 ICH 的 C57BL/6 小鼠施用尼古丁。ICH 后第 7 天和第 14 天，通过增加的 CD31 免疫阳性区域显示，通过这两种途径施用尼古丁增强了血肿影响区域内的血管生成。针对 CD31 和增殖细胞核抗原的双重免疫荧光组织化学显示，尼古丁增加了血肿内新生成的血管内皮细胞的数量。尽管血管生成增强，根据伊文思蓝外渗评估，尼古丁不会使 ICH 后血管通透性恶化。尼古丁的这些作用伴随着 ICH 后 7 天血肿中存活神经元数量的增加。出乎意料的是，尼古丁不会增加大脑中血管内皮生长因子 mRNA 的表达，也不会增强从骨髓中募集内皮祖细胞。这些结果表明，尼古丁通过不同于其对外周组织血管生成作用的机制，增强了 ICH 后大脑中的血管生成。尼古丁不会增加大脑中血管内皮生长因子 mRNA 的表达，也不会增强从骨髓中募集内皮祖细胞。这些结果表明，尼古丁通过不同于其对外周组织血管生成作用的机制，增强了 ICH 后大脑中的血管生成。尼古丁不会增加大脑中血管内皮生长因子 mRNA 的表达，也不会增强从骨髓中募集内皮祖细胞。这些结果表明，尼古丁通过不同于其对外周组织血管生成作用的机制，增强了 ICH 后大脑中的血管生成。