Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea.
Department of Biomedical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea.
Stem Cell Res Ther. 2018 Nov 9;9(1):309. doi: 10.1186/s13287-018-1011-1.
The positive effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and minocycline on ischemic stroke models have been well described through numerous studies. The aim of this study was to evaluate the effectiveness of combination therapy of hBM-MSCs with minocycline in a middle cerebral artery occlusion rat model.
Forty male Sprague-Dawley rats were enrolled in this study. After right middle cerebral artery occlusion, rats were randomly assigned to one of four groups: control, minocycline, hBM-MSCs, or hBM-MSCs with minocycline. Rotarod test, adhesive-removal test, and modified neurological severity score grading were performed before and 1, 7, 14, 21, and 28 days after right middle cerebral artery occlusion. All rats were sacrificed at day 28. The volume of the infarcted area was measured with triphenyl tetrazolium chloride staining. Neuronal nuclear antigen (NeuN)- and vascular endothelial growth factor (VEGF)-positive cells in the ischemic boundary zone were assessed by immunofluorescence.
Neurological outcome in the adhesive-removal test and rotarod test and modified neurological severity score were better in the combination therapy group than in the monotherapy and control groups. The volume of the infarcted area was smaller in the combination group compared with the others. The proportions of NeuN- and VEGF-positive cells in the ischemic boundary were highest in the combination therapy group.
Early combination therapy of hBM-MSCs with minocycline in an ischemic stroke model may enhance neurological recovery, reduce the volume of the infarcted area, and promote the expression of NeuN and VEGF in ischemic boundary cells.
大量研究表明，人骨髓间充质干细胞（hBM-MSCs）和米诺环素对缺血性中风模型具有积极作用。本研究旨在评估 hBM-MSCs 与米诺环素联合治疗大脑中动脉闭塞大鼠模型的效果。
本研究纳入了 40 只雄性 Sprague-Dawley 大鼠。大脑中动脉闭塞后，大鼠被随机分为 4 组：对照组、米诺环素组、hBM-MSCs 组和 hBM-MSCs 联合米诺环素组。在大脑中动脉闭塞前和 1、7、14、21 和 28 天后进行旋转棒试验和粘贴物去除试验，并进行改良神经功能缺损评分。所有大鼠于第 28 天处死。用氯化三苯基四氮唑染色测量梗死面积。通过免疫荧光法评估缺血边界区神经元核抗原（NeuN）和血管内皮生长因子（VEGF）阳性细胞。
在粘贴物去除试验和旋转棒试验中的神经功能结局以及改良神经功能缺损评分中，联合治疗组均优于单药治疗组和对照组。与其他组相比，联合治疗组的梗死面积更小。缺血边界区的 NeuN 和 VEGF 阳性细胞比例在联合治疗组中最高。
在缺血性中风模型中早期联合应用 hBM-MSCs 和米诺环素治疗可能会增强神经功能恢复，减少梗死面积，并促进缺血边界细胞中 NeuN 和 VEGF 的表达。
