Related Experiment Video
Updated: Mar 3, 2026
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Global Transcriptomic Profiling of Cortex and Striatum: Cerebral Injury after Ischemia/Reperfusion in a Mouse Model
Zhenying Zhao1, Zhiqiang Lu2, Xiuying Sun3
1Department of Pharmacy, Tianjin Union Medical Center, Tianjin, China; School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Objective:
This study aims to investigate the molecular mechanism of injury development in the cortex and the striatum after cerebral ischemia/reperfusion (I/R).
Methods:
Gene expression data (GSE23160) in the cortex and the striatum of an intraluminal middle cerebral artery occlusion-I/R mouse model (N = 12) and sham controls (N = 4) were downloaded from the Gene Expression Omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between the I/R (2, 8, and 24 hours) and control groups. Correlation analysis was then performed to identify the highly correlated differentially expressed genes (HCDEGs). STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network of HCDEGs. Furthermore, Venny 2.0 was used to identify common overlapped DEGs whose transcription factors (TFs) were predicted using iRegulon in Cytoscape.
Results:
For the cortex and the striatum, 2295 and 2282 DEGs were respectively identified between the I/R group and the controls, and were classified into 3 and 2 correlation modules. For each module, a PPI network was constructed, and Toll-like receptor 2 (Tlr2, degree = 25), interleukin 1β (Il1b, degree = 21), and heme oxygenase-1 (Hmox1, degree = 17) had high connective degrees. Furthermore, 29 common overlapped DEGs were found across time and tissue, which might be targeted by 13 TFs. Especially, Tlr2, Il1b, and Hmox1 were targeted by myeloblastosis protein (Myb, target count = 16) and FBJ osteosarcoma protein (Fos, target count = 15). Moreover, plasminogen activator urokinase receptor (Plaur) was targeted by Fos, and it was an HCDEG in correlation modules of both cortex and striatum. Upregulation of Tlr2, Il1b, Hmox1, and Plaur in I/R injury was confirmed using quantitative polymerase chain reaction and immunohistochemical staining.
Conclusion:
Tlr2, Il1b, Hmox1, and Plaur regulated by Myb and Fos might participate in cortex and striatum injury after cerebral I/R.
Insights
This study reveals key genes, including Toll-like receptor 2 and interleukin 1β, involved in brain injury after cerebral ischemia. These genes, regulated by Myb and Fos, offer potential therapeutic targets for stroke recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Cerebral ischemia/reperfusion (I/R) injury affects the brain's cortex and striatum.
- Understanding the molecular mechanisms of I/R injury is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the molecular mechanisms underlying brain injury in the cortex and striatum following cerebral ischemia/reperfusion (I/R).
Main Methods:
- Utilized gene expression data from a mouse model of middle cerebral artery occlusion-I/R.
- Identified differentially expressed genes (DEGs) and constructed protein-protein interaction (PPI) networks.
- Predicted transcription factors (TFs) targeting key DEGs.
Main Results:
- Identified thousands of DEGs in both cortex and striatum post-I/R.
- Highlighted Toll-like receptor 2 (Tlr2), interleukin 1β (Il1b), and heme oxygenase-1 (Hmox1) as highly connected genes in PPI networks.
- Found 29 common DEGs targeted by 13 TFs, with Tlr2, Il1b, and Hmox1 notably regulated by Myb and Fos. Plasminogen activator urokinase receptor (Plaur) was also identified.
Conclusions:
- Tlr2, Il1b, Hmox1, and Plaur, potentially regulated by Myb and Fos, play a role in cerebral I/R injury in the cortex and striatum.
- These findings suggest potential molecular targets for mitigating I/R-induced brain damage.
