CO-Releasing Molecule (CORM)-3 Ameliorates Spinal Cord-Blood Barrier Disruption Following Injury to the Spinal Cord

Gang Zheng; Fanghong Zheng; Zucheng Luo; Haiwei Ma; Dongdong Zheng; Guangheng Xiang; Cong Xu; Yifei Zhou; Yaosen Wu; Naifeng Tian; Yan Wu; Tan Zhang; Wenfei Ni; Sheng Wang; Huazi Xu; Xiaolei Zhang

doi:10.3389/fphar.2020.00761

CO-Releasing Molecule (CORM)-3 Ameliorates Spinal Cord-Blood Barrier Disruption Following Injury to the Spinal Cord

Front Pharmacol. 2020 Jun 4:11:761. doi: 10.3389/fphar.2020.00761. eCollection 2020.

Authors

Gang Zheng^{1

2}, Fanghong Zheng^{1

2

3}, Zucheng Luo^{1

2}, Haiwei Ma^{1

2}, Dongdong Zheng⁴, Guangheng Xiang^{1

2}, Cong Xu^{1

2}, Yifei Zhou^{1

2

3}, Yaosen Wu^{1

2

3}, Naifeng Tian^{1

2

3}, Yan Wu⁵, Tan Zhang⁶, Wenfei Ni^{1

2}, Sheng Wang^{1

2

3}, Huazi Xu^{1

2

3}, Xiaolei Zhang^{1

2

3

7}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
² Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou, China.
³ The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
⁴ Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
⁵ Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Wenzhou, China.
⁶ Department of Orthopaedics, Shaoxing People's Hospital, Shaoxing, Wenzhou, China.
⁷ Department of Orthopaedics, Chinese Orthopaedic Regenerative Medicine Society, Hangzhou, China.

Abstract

Spinal cord injury (SCI) is a clinical tough neurological problem without efficient cure currently. Blood-spinal cord barrier (BSCB) interruption is not only a crucial pathological feature for SCI process but is a possible target for future SCI treatments; however, few treatments have been developed to intervene BSCB. In the present study, we intravenously injected CO-releasing molecule3 (CORM-3), a classical exogenous CO donor, to the rats experiencing SCI and assessed its protection on BSCB integrity in rats. Our results demonstrated that the exogenous increasing of CO by CORM-3 blocked the tight junction (TJ) protein degeneration and neutrophils infiltration, subsequently suppressed the BSCB damage and improved the motor recovery after SCI. And we certified that the CO-induced down-regulation of MMP-9 expression and activity in neutrophil might be associated with the NF-κB signaling. Taken together, our study indicates that CO-releasing molecule (CORM)-3 ameliorates BSCB after spinal cord injury.

Keywords: CO-releasing molecule-3; blood spinal cord barrier; carbon monoxide; neutrophil; spinal cord injury.