Department of Biology, University of Iowa, Iowa City, Iowa, USA.
Glia. 2012 Nov;60(11):1747-60. doi: 10.1002/glia.22394. Epub 2012 Jul 28.
As brain-resident immune cells, microglia (MG) survey the brain parenchyma to maintain homeostasis during development and following injury. Research in perinatal stroke, a leading cause of lifelong disability, has implicated MG as targets for therapeutic intervention during stroke. Although MG responses are complex, work in developing rodents suggests that MG limit brain damage after stroke. However, little is known about how energy-limiting conditions affect MG survival and mobility (motility and migration) in developing brain tissues. Here, we used confocal time-lapse imaging to monitor MG viability and mobility during hypoxia or oxygen-glucose deprivation (OGD) in hippocampal tissue slices derived from neonatal GFP-reporter mice (CX3CR1(GFP/+) ). We found that MG remain viable for at least 6 h of hypoxia but begin to die after 2 h of OGD, while both hypoxia and OGD reduce MG motility. Unexpectedly, some MG retain or recover motility during OGD and can engulf dead cells. Additionally, MG from younger neonates (P2-P3) are more resistant to OGD than those from older ones (P6-P7), indicating increasing vulnerability with developmental age. Finally, transient (2 h) OGD also increases MG death, and although motility is rapidly restored after transient OGD, it remains below control levels for many hours. Together, these results show that MG in neonatal mouse brain tissues are vulnerable to both transient and sustained OGD, and many MG die within hours after onset of OGD. Preventing MG death may, therefore, provide a strategy for promoting tissue restoration after stroke.
作为驻留于大脑的免疫细胞，小胶质细胞（MG）在大脑发育和损伤后维持脑内环境的稳态。在围产期卒中（一种导致终身残疾的主要原因）的研究中，MG 被认为是卒中期间治疗干预的靶点。尽管 MG 的反应很复杂，但在发育中的啮齿动物中的研究表明，MG 可以限制卒中后的脑损伤。然而，对于能量限制条件如何影响发育中的脑组织中的 MG 存活和迁移（运动性和迁移性），目前所知甚少。在这里，我们使用共聚焦延时成像来监测海马组织切片中来自新生 GFP 报告小鼠（CX3CR1(GFP/+)）的 MG 在缺氧或氧葡萄糖剥夺（OGD）期间的活力和迁移性。我们发现，MG 在缺氧条件下至少可以存活 6 小时，但在 OGD 2 小时后开始死亡，而缺氧和 OGD 都会降低 MG 的运动性。出乎意料的是，一些 MG 在 OGD 期间仍然保持或恢复运动性，并且可以吞噬死细胞。此外，来自年轻新生鼠（P2-P3）的 MG 比来自年长新生鼠（P6-P7）对 OGD 的抵抗力更强，这表明随着发育年龄的增加，MG 的易感性增加。最后，短暂（2 小时）OGD 也会增加 MG 的死亡，尽管在短暂 OGD 后 MG 的运动性迅速恢复，但在数小时内仍低于对照水平。总的来说，这些结果表明，新生鼠脑组织中的 MG 对短暂和持续的 OGD 都很敏感，并且在 OGD 发生后的数小时内，许多 MG 就会死亡。因此，防止 MG 死亡可能为卒中后促进组织修复提供一种策略。
