1 Meridigen Biotech Co., Ltd., Neihu, Taipei City, Taiwan.
2 Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan.
Cell Transplant. 2017 Nov;26(11):1798-1810. doi: 10.1177/0963689717728936.
Microglia are the first source of a neuroinflammatory cascade, which seems to be involved in every phase of stroke-related neuronal damage. Two weeks after transient middle cerebral artery occlusion (MCAO), vehicle-treated rats displayed higher numbers of total ionized calcium-binding adaptor molecule 1 (Iba-1)-positive cells, greater cell body areas of Iba-1-positive cells, and higher numbers of hypertrophic Iba-1-positive cells (with a cell body area over 80 μm) in the ipsilateral ischemic brain regions including the frontal cortex, striatum, and parietal cortex. In addition, MCAO decreased the number of migrating neuroblasts (or DCX- and 5-ethynyl-2'-deoxyuridine-positive cells) in the cortex, subventricular zone, and hippocampus of the ischemic brain, followed by neurological injury (including brain infarct and neurological deficits). Intravenous administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs; 1 × 10 or 4 × 10) at 24 h after MCAO reduced neurological injury, decreased the number of hypertrophic microglia/macrophages, and increased the number of newborn neurons in rat brains. Thus, the accumulation of hypertrophic microglia/macrophages seems to be detrimental to neurogenesis after stroke. Treatment with hUC-MSCs preserved adult newborn neurons and reduced functional impairment after transient cerebral ischemia by reducing the number of hypertrophic microglia/macrophages.
小胶质细胞是神经炎症级联反应的最初来源，该级联反应似乎涉及与中风相关的神经元损伤的每个阶段。短暂性大脑中动脉闭塞（MCAO）后 2 周，载体处理的大鼠在同侧缺血脑区（包括额皮质、纹状体和顶皮质）中显示出更高数量的总离子钙结合衔接蛋白 1（Iba-1）阳性细胞、更大的 Iba-1 阳性细胞体面积和更高数量的肥大 Iba-1 阳性细胞（细胞体面积超过 80μm）。此外，MCAO 减少了缺血大脑皮质、室下区和海马中的迁移神经前体细胞（或 DCX 和 5-乙炔基-2'-脱氧尿苷阳性细胞）的数量，随后发生神经损伤（包括脑梗死和神经功能缺损）。MCAO 后 24 小时静脉内给予人脐带源间充质干细胞（hUC-MSCs；1×10 或 4×10）可减轻神经损伤、减少肥大小胶质细胞/巨噬细胞的数量，并增加大鼠大脑中新神经元的数量。因此，肥大小胶质细胞/巨噬细胞的积累似乎对中风后的神经发生有害。hUC-MSCs 的治疗通过减少肥大小胶质细胞/巨噬细胞的数量来保存成年新生神经元并减轻短暂性脑缺血后的功能障碍。
