Abstract TMP67: Microglia Transplantation Reduces Stroke Injury
Microglia are activated after stroke and may contribute to ischemic brain injury by producing mediators such as inflammatory cytokines and free radicals that are toxic to neurons. Microglia are also likely responsible for the influx of peripheral immune cells after stroke, which further exacerbate injury. In contrast, there is increasing evidence that microglia can also be protective, as ablating microglia before stroke increases infarct size (1) and arterial injection of microglia during global ischemia reduces neuronal death (2). We tested whether increasing the number of resident microglia by transplantation would convey protection from ischemic stroke.
We injected 20,000 primary cultured microglia into the striatum of adult male C57Bl/6 mice. Control groups were injected with a similar number of cultured astrocytes or received no injection. Additional mice were injected with eGFP expressing microglia to allow visualization of transplanted cells. After 14 days recovery, mice underwent 60 minutes of transient middle cerebral artery occlusion. Cerebral blood flow was monitored by laser Doppler. Infarct size was measured by TTC staining 24 hours after reperfusion and expressed as % of contralateral structure.
Transplanted microglia survived and were present in the striatum 14 days after the injection. Infarct size was significantly reduced by microglia transplantation, both in the infarct core (striatum, 69% vs. 80% control) as well as the penumbra (cortex, 42% vs. 52%, P<0.05). Transplantation of astrocytes, in contrast, had no effect on infarct size. Cerebral blood flow was not different between groups.
The number of resident microglia in mouse brain can be increased by transplantation of microglia, which survive for several weeks after injection. Infarct size is reduced after transplantation of microglia. This is likely caused by increased microglial production of neuroprotective and anti-inflammatory mediators after stroke, such as insulin-like growth factor (1) or interleukin-10. Further studies will identify the microglial mediators that are responsible for the observed protection. They may offer new therapeutic options to reduce injury after stroke.
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Imai et al. JCBFM 2007
- © 2012 by American Heart Association, Inc.