Effects of oxygen-glucose deprivation on microglial mobility and viability in developing mouse hippocampal tissues.
Effects of oxygen-glucose deprivation on microglial mobility and viability in developing mouse hippocampal tissues.
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DOI：
10.1002/glia.22394
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发表时间：
2012-11
期刊：
影响因子：
6.2
通讯作者：
Dailey, Michael E.
中科院分区：
文献类型：
--
作者：
Eyo, Ukpong;Dailey, Michael E.
小胶质细胞（MG）作为脑内驻留的免疫细胞，在发育过程中和脑损伤后监测脑实质以维持稳态。围产期卒中是导致终身残疾的主要原因，最近的研究表明MG是卒中进展期间治疗干预的靶点。虽然MG反应是复杂的，但在发育中的啮齿动物中的工作表明，MG限制脑损伤并促进中风后的恢复。然而，关于能量限制条件如何影响MG存活和发育中脑组织的流动性知之甚少。在这里，我们使用共聚焦时间推移成像监测MG的活力和运动在缺氧或氧-葡萄糖剥夺（OGD）的新生海马组织切片来自GFP报告小鼠（CX 3CR 1GFP/+）。我们发现P5-P7新生儿组织中的MG在至少6小时的缺氧中仍然存活，但在OGD 2小时后开始死亡。缺氧和OGD均降低MG运动。出乎意料的是，一些MG在OGD期间保留或恢复运动性，并且这些活性MG可以接触并吞噬死细胞。来自年轻新生儿（P2-P3）的MG比来自年长新生儿的MG对OGD更具抵抗力，表明随着发育年龄的增加，MG的脆弱性增加。最后，我们表明，短暂的（2小时）OGD减少MG运动，迁移和活力。虽然MG运动性在短暂OGD后迅速恢复，但它仍低于对照水平许多小时。总之，这些结果表明，新生小鼠脑组织中的MG易受短暂和持续OGD的影响，许多MG在OGD发作后数小时内死亡。因此，预防MG死亡可能为促进卒中后组织恢复提供一种策略。
As brain-resident immune cells, microglia (MG) survey the brain parenchyma to maintain homeostasis during development and following injury. Recent work in perinatal stroke, a leading cause of lifelong disability, has implicated MG as targets for therapeutic intervention during stroke progression. Although MG responses are complex, work in developing rodents suggests that MG limit brain damage and promote recovery after stroke. However, little is known about how energy-limiting conditions affect MG survival and mobility in developing brain tissues. Here, we used confocal time-lapse imaging to monitor MG viability and motility during hypoxia or oxygen-glucose deprivation (OGD) in neonatal hippocampal tissue slices derived from GFP-reporter mice (CX3CR1GFP/+). We found that MG in P5-P7 neonatal tissues remain viable for at least 6hr of hypoxia but begin to die after 2hr of OGD. Both hypoxia and OGD reduced MG motility. Unexpectedly, some MG retain or recover motility during OGD, and these active MG can contact and engulf dead cells. MG from younger neonates (P2-P3) are more resistant to OGD than those from older ones, indicating increasing vulnerability with developmental age. Finally, we show that transient (2hr) OGD reduces MG motility, migration, and viability. Although MG 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.
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DOI：
10.1523/jneurosci.2102-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Faustino JV;Wang X;Johnson CE;Klibanov A;Derugin N;Wendland MF;Vexler ZS
通讯作者：
Vexler ZS
影响因子：
4.2
作者：
Dibaj, Payam;Steffens, Heinz;Schomburg, Eike D.
通讯作者：
Schomburg, Eike D.
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
3.5
作者：
Kitamura, Y;Takata, K;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
3.3
作者：
Hayashi, Y.;Tomimatsu, Y.;Nakanishi, H.
通讯作者：
Nakanishi, H.