Ischemia/Reperfusion Induces Interferon-Stimulated Gene Expression in Microglia

Stroke is the fifth leading cause of death in the United States and is a leading cause of serious long-term disability worldwide. Innate immune responses are critical in stroke pathophysiology, and microglia are key cellular effectors in the CNS response to ischemia/reperfusion. Using a transcriptional analysis approach, we identified a robust interferon (IFN)-stimulated gene response within microglia exposed to ischemia/reperfusion. We have demonstrated that these responses are dependent on innate immune signaling components including Toll-like receptor-4 and type I IFNs. We have also elucidated several novel ischemia/reperfusion-induced microglial signaling mechanisms. Transient (15 min) middle cerebral artery occlusion followed by 72 h reperfusion (tMCAO/R) or sham surgery was performed under isoflurane inhalational anesthesia on 12- to 14-week-old male WT or TLR4−/− mice using the transient intraluminal filament method. RNA was extracted from ex vivo sorted microglia from ipsilateral cortex and profiled by microarray. Statistical analysis was performed using Bioconductor limma package. Results were validated by quantitative RT-PCR.