Roles of Microglia In Developing brain functions

小胶质细胞是大脑中的巨噬细胞样细胞，是一种多功能细胞。我发现小胶质细胞对大脑有特定的亲和力，但巨噬细胞没有。将荧光标记的小胶质细胞注射到成年雄性大鼠的主动脉中，在脑中观察到许多荧光细胞，在肝脏中观察到很少的荧光细胞。这些结果表明，小胶质细胞具有特定的亲和力和迁移到大脑的能力。为了确定人工修饰的基因是否可以通过我们的新技术转移到脑内，用LacZ基因表达载体横切小胶质细胞，并将其注射到大鼠的主动脉中。X-Gal染色显示，注射LacZ基因表达载体的大鼠脑组织中可见大量蓝色细胞。脑组织切片中检测到β-半乳糖苷酶的活性。接下来，我们利用一个缺血性海马区损伤模型，比较了系统注射的小胶质细胞在正常脑和缺血脑中的迁移。将小胶质细胞注入沙土鼠脑缺血再灌流损伤模型。常规组织学分析和dUTP缺口末端标记法(TUNEL)证实锥体神经元迟发性死亡。组织化学证实，迁移到海马区缺血灶中的染料标记细胞群为小胶质细胞。在本模型中，外周注射的小胶质细胞表现出对缺血性脑损伤的特异性亲和力，并且不会加剧缺血性神经元损伤。相反，我们发现了外源性小胶质细胞对锥体神经元延迟性死亡的保护作用。因此，我们认为在短暂性全脑缺血损伤后，小胶质细胞有可能被用作携带治疗性基因和/或修复中枢神经系统药物的载体。

Microglia, macrophage-like cells in the brain, are multi-functional cells. I found that microglia had a specific affinity to the brain but macrophages did not. When fluorescent-labeled microglial cells were injected into the aorta of an adult male rat, many fluorescent cells were observed in the brain and few were seen in the liver. These results suggest that microglia have a specific affinity and the ability to migrate to the brain. To determine whether an artificially modified gene could be transferred into brain using our novel technique, microglia were transected with a lacZ gene expression vector and were injected into the aorta of rats. When the brain sections were stained with X-gal, many blue cells were observed thoughout the brains prepared from rats injected with the cells carrying a lacZ gene expression vector. The activity of b-galactosidase was detected in the brain sections from these rats. Next, we compared migration of systemically injected microglia into normal brain vs. ischemic brain using a model of ischemic hippocampal lesion. Microglia were injected intra-arterially into Mongolian gerbils subjected to ischemia reperfusion neuronal injury. Delayed death of pyramidal neurons was confirmed by conventional histological analysis and dUTP nick end labeling (TUNEL) method. Clusters of dye-tagged cells migrating into the hippocampal ischemic lesions were confirmed histochemically to be microglia. Peripherally7 injected microglia exhibit specific affinity for ischemic brain lesions and does not exacerbate ischemic neuronal injury in the present model. Rather we found protective effects of exogenous microglia on delayed death of pyramidal neurons. Therefore, we suggest that microglia may have a potential to be used as a piggy-back ride to deliver therapeutic genes and/of drugs for CNS repair following transitory global ischemic insult.