Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke

作者：Zhijuan Cao, Sean Harvey, Terrance Chiang, Aulden Foltz, Alex G. Lee, Michelle Cheng, Gary K. Steinberg · 发表于：Stroke · 年份：2021 · DOI：10.1161/strokeaha.120.032402 · 被引用次数：69 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Inflammation biomarkers and pathways、Intracerebral and Subarachnoid Hemorrhage Research

Background and Purpose: Stroke disrupts neuronal functions in both local and remotely connected regions, leading to network-wide deficits that can hinder recovery. The thalamus is particularly affected, with progressive development of neurodegeneration accompanied by inflammatory responses. However, the complexity of the involved inflammatory responses is poorly understood. Herein we investigated the spatiotemporal changes in the secondary degenerative thalamus after cortical stroke, using targeted transcriptome approach in conjunction with histology and flow cytometry. Methods: Cortical ischemic stroke was generated by permanent occlusion of the left middle cerebral artery in male C57BL6J mice. Neurodegeneration, neuroinflammatory responses, and microglial activation were examined in naive and stroke mice at from poststroke days (PD) 1 to 84, in both ipsilesional somatosensory cortex and ipsilesional thalamus. NanoString neuropathology panel (780 genes) was used to examine transcriptome changes at PD7 and PD28. Fluorescence activated cell sorting was used to collect CD11c + microglia from ipsilesional thalamus, and gene expressions were validated by quantitative real-time polymerase chain reaction. Results: Neurodegeneration in the thalamus was detected at PD7 and progressively worsened by PD28. This was accompanied by rapid microglial activation detected as early as PD1, which preceded the neurodegenerative changes. Transcriptome analysis showed higher number of differentia...