RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke

作者：Masaki Ito, Markus Aswendt, Alex G. Lee, Shunsuke Ishizaka, Zhijuan Cao, Eric H. Wang, S. Lévy, Daniel Smerin, Jennifer A. McNab, Michael Zeineh, Christoph Leuze, Maged Goubran, Michelle Cheng, Gary K. Steinberg · 发表于：Stroke · 年份：2018 · DOI：10.1161/strokeaha.118.021508 · 被引用次数：52 · 研究领域：Stroke Rehabilitation and Recovery、Neuroinflammation and Neurodegeneration Mechanisms、Acute Ischemic Stroke Management

Background and Purpose- Many restorative therapies have been used to study brain repair after stroke. These therapeutic-induced changes have revealed important insights on brain repair and recovery mechanisms; however, the intrinsic changes that occur in spontaneously recovery after stroke is less clear. The goal of this study is to elucidate the intrinsic changes in spontaneous recovery after stroke, by directly investigating the transcriptome of primary motor cortex in mice that naturally recovered after stroke. Methods- Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion. Functional recovery was evaluated using the horizontal rotating beam test. A novel in-depth lesion mapping analysis was used to evaluate infarct size and locations. Ipsilesional and contralesional primary motor cortices (iM1 and cM1) were processed for RNA-sequencing transcriptome analysis. Results- Cluster analysis of the stroke mice behavior performance revealed 2 distinct recovery groups: a spontaneously recovered and a nonrecovered group. Both groups showed similar lesion profile, despite their differential recovery outcome. RNA-sequencing transcriptome analysis revealed distinct biological pathways in the spontaneously recovered stroke mice, in both iM1 and cM1. Correlation analysis revealed that 38 genes in the iM1 were significantly correlated with improved recovery, whereas 74 genes were correlated in the cM1. In particular, ingenuity pathway analysis highlighted the in...