Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennnoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
Biochem Biophys Res Commun. 2013 Mar 1;432(1):182-7. doi: 10.1016/j.bbrc.2013.01.013. Epub 2013 Jan 11.
Although fibroblast growth factor 2 (FGF2) is a promising agent for treating brain infarction, current methods of FGF2 administration are associated with a short circulating half-life. An FGF2 apatite coating was developed as a slow-releasing drug delivery system (DDS) by forming an FGF2/calcium phosphate composite layer. Hydroxyapatite was coated with high or low doses of FGF2, denoted as FGF-high and FGF-low. This study investigated the efficacy of the coating as angiogenesis therapy for brain infarction. Rats were subjected to permanent occlusion of the middle cerebral artery, an FGF2 apatite-coated implant was inserted, and the rat brains were removed 2 weeks after implantation. Rats in groups treated with FGF-high had significantly smaller areas of brain infarction, particularly in the external capsule and the lateral side of the putamen, and better capillary density than rats in groups treated with non-FGF2 apatite-coated implants. Histologic analysis indicated that the new vessels were larger and had thicker walls in the FGF2 apatite-coated groups than in the non-FGF2 groups. Fluorescence immunohistochemistry of the peri-infarction region showed that FGF2 released from FGF2 apatite-coated implants might have biological activity. Moreover, fluorescence immunohistochemistry showed that released FGF2 influenced microglia cells. This new FGF2 DDS involving an FGF2 apatite coating can prevent infarction of the penumbra through the multipotential effects of FGF2.
尽管成纤维细胞生长因子 2（FGF2）是治疗脑梗死的有前途的药物，但目前的 FGF2 给药方法与较短的循环半衰期有关。通过形成 FGF2/磷酸钙复合材料层，开发了 FGF2 磷灰石涂层作为一种缓释药物递送系统（DDS）。用高剂量或低剂量的 FGF2 对羟基磷灰石进行涂层，分别表示为 FGF-高和 FGF-低。本研究探讨了涂层作为脑梗死血管生成治疗的效果。对大鼠进行大脑中动脉永久性闭塞，插入 FGF2 磷灰石涂层植入物，植入后 2 周取出大鼠大脑。与未用 FGF2 磷灰石涂层处理的植入物治疗的大鼠相比，用 FGF-高处理的大鼠的脑梗死面积明显更小，特别是在外侧囊和壳核的外侧，并且毛细血管密度更好。组织学分析表明，在 FGF2 磷灰石涂层组中，新血管更大，壁更厚。在梗死周边区的荧光免疫组织化学显示，从 FGF2 磷灰石涂层植入物释放的 FGF2 可能具有生物活性。此外，荧光免疫组织化学显示释放的 FGF2 影响小胶质细胞。这种新的 FGF2 DDS 涉及 FGF2 磷灰石涂层，可以通过 FGF2 的多潜能作用来防止半影区的梗死。
