Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
J Cereb Blood Flow Metab. 2011 May;31(5):1263-71. doi: 10.1038/jcbfm.2010.213. Epub 2010 Dec 15.
Intra-arterial (IA) injection represents an experimental avenue for minimally invasive delivery of stem cells to the injured brain. It has however been reported that IA injection of stem cells carries the risk of reduction in cerebral blood flow (CBF) and microstrokes. Here we evaluate the safety of IA neural progenitor cell (NPC) delivery to the brain. Cerebral blood flow of rats was monitored during IA injection of single cell suspensions of NPCs after stroke. Animals received 1 × 10(6) NPCs either injected via a microneedle (microneedle group) into the patent common carotid artery (CCA) or via a catheter into the proximally ligated CCA (catheter group). Controls included saline-only injections and cell injections into non-stroked sham animals. Cerebral blood flow in the microneedle group remained at baseline, whereas in the catheter group a persistent (15 minutes) decrease to 78% of baseline occurred (P<0.001). In non-stroked controls, NPCs injected via the catheter method resulted in higher levels of Iba-1-positive inflammatory cells (P=0.003), higher numbers of degenerating neurons as seen in Fluoro-Jade C staining (P<0.0001) and ischemic changes on diffusion weighted imaging. With an appropriate technique, reduction in CBF and microstrokes do not occur with IA transplantation of NPCs.
动脉内 (IA) 注射是一种将干细胞微创递送至受损大脑的实验途径。然而,据报道,IA 注射干细胞存在降低脑血流 (CBF) 和微中风的风险。在这里,我们评估了将神经祖细胞 (NPC)IA 递送至大脑的安全性。在中风后,通过微针 (微针组) 将 NPC 的单细胞混悬液IA 注射时监测大鼠的脑血流。动物接受了 1×10(6)个 NPC,要么通过微针注射到通畅的颈总动脉 (CCA) 中(微针组),要么通过导管注射到结扎的 CCA 近端(导管组)。对照组包括仅注射盐水和注射到非中风假手术动物中的细胞。微针组的脑血流保持在基线水平,而导管组则持续(15 分钟)下降到基线的 78%(P<0.001)。在未中风的对照组中,通过导管法注射的 NPC 导致更高水平的 Iba-1 阳性炎症细胞(P=0.003),氟罗丹明 C 染色显示更多的神经元变性(P<0.0001)和扩散加权成像上的缺血变化。通过适当的技术,IA 移植 NPC 不会导致 CBF 降低和微中风。