Shichinohe Hideo, Yamauchi Tomohiro, Saito Hisayasu, Houkin Kiyohiro, Kuroda Satoshi
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Acta Neurobiol Exp (Wars). 2013;73(3):354-63. doi: 10.55782/ane-2013-1942.
This study was aimed to clarify if the bone marrow stromal cells (BMSCs) significantly improve functional outcome after lacunar stroke when stereotactically transplanted into the brain. Ouabain, a Na/K ATPase pump inhibitor, was stereotactically injected into the right striatum of Wistar rats. One week later, the superparamagnetic iron oxide (SPIO)-labeled rat BMSCs (n=7) or vehicle (n=8) were stereotactically transplanted into the left striatum. Using rotarod test, motor function was serially evaluated through the experiment. A 7.0-T MR apparatus was employed to serially monitor the migration of BMSCs in the host brain. Histological analysis was performed at 7 weeks after ouabain injection, i.e., 6 weeks after BMSC transplantation. Ouabain injection yielded the reproducible, focal lesion in the right striatum, causing continuous motor dysfunction throughout the experiment. BMSC transplantation significantly enhanced the recovery of motor function after ouabain injection. MR imaging demonstrated that the BMSCs aggressively migrated towards the lesion through the corpus callosum. Histological analysis supported the findings on MRI. The BMSCs significantly enhanced the neurogenesis in the subventricular zone (SVZ) on both sides. Some of them also expressed neuronal or astrocytic phenotypes in the neocortex, SVZ, corpus callosum, and peri-lesion area. These findings strongly suggest that the BMSCs may serve therapeutic impacts on lacunar stroke when stereotactically transplanted at clinically relevant timing.
本研究旨在阐明骨髓基质细胞(BMSCs)立体定向移植到脑内后是否能显著改善腔隙性脑卒后的功能结局。哇巴因是一种钠钾ATP酶泵抑制剂,将其立体定向注射到Wistar大鼠的右侧纹状体。一周后,将超顺磁性氧化铁(SPIO)标记的大鼠BMSCs(n = 7)或赋形剂(n = 8)立体定向移植到左侧纹状体。通过转棒试验,在整个实验过程中连续评估运动功能。使用7.0-T MR设备连续监测BMSCs在宿主脑内的迁移情况。在注射哇巴因7周后,即BMSC移植6周后进行组织学分析。注射哇巴因在右侧纹状体产生了可重复的局灶性病变,在整个实验过程中导致持续的运动功能障碍。BMSC移植显著促进了哇巴因注射后运动功能的恢复。MR成像显示BMSCs通过胼胝体向病变部位大量迁移。组织学分析支持了MRI的结果。BMSCs显著增强了双侧脑室下区(SVZ)的神经发生。其中一些细胞还在新皮层、SVZ、胼胝体和病变周围区域表达神经元或星形胶质细胞表型。这些发现强烈表明,在临床相关时机进行立体定向移植时,BMSCs可能对腔隙性脑卒具有治疗作用。