Significant changes in circular RNA in the mouse cerebral cortex around an injury site after traumatic brain injury

Zhihao Chen  ¹ , Hong Wang  ¹ , Jianjun Zhong  ² , Junqing Yang  ¹ , Rami Darwazeh  ³ , Xiaocui Tian  ¹ , Zhijian Huang  ³ , Li Jiang  ³ , Chongjie Cheng  ³ , Yue Wu  ³ , Zongduo Guo  ³ , Xiaochuan Sun  ⁴

Affiliations

• ¹ Department of Pharmacology, Chongqing Medical University, The Key Labratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
• ² Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: zjjcom682161@126.com.
• ³ Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
• ⁴ Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: sunxch1445@qq.com.

Abstract

Background and objective: Circular RNA (circRNA) is an important type of non-coding RNA that has not been widely researched in traumatic brain injury (TBI). The present study aimd to detect the altered circRNA expression around an injury site in the mouse cerebral cortex after TBI and explore its potential functions.

Method: C57BL/6 mice were used to construct a controlled cortical impact (CCI) model to simulate TBI. At 24 h post-TBI, the cortex around the injury site was collected, and the total RNA was extracted to perform RNA sequencing (RNA-seq). The differentially expressed circRNAs were determined according to the following criteria: |log₂^{(fold change)}| > 1, P < .05 and FDR < 0.05. Among them, circRNA chr8_87,859,283-87,904,548 was preliminarily explored to determine its function.

Results: A total of 8036 altered circRNAs were discovered, and among them, 16 were significantly changed (5 up-regulated and 11 down-regulated). The circRNA chr8_87,859,283-87,904,548 significantly increased by approximately 4 times in the cerebral cortex around the injury site after TBI and promoted neuro-inflammation through increasing the CXCR2 protein by sponging mmu-let-7a-5p. As a result, the increased circRNA chr8_87,859,283-87,904,548 blocked the restoration of neurological function after TBI.

Conclusion: Many circRNAs are significantly up-regulated or down-regulated in the traumatic cerebral penumbra cortex after TBI. Among them, the circRNA chr8_87,859,283-87,904,548 potentially plays a pro-inflammatory role, which may have a deleterious effect on neurological restoration after TBI. .

Keywords: CXCR2; Circular RNA; RNA-seq; TBI; miRNA.