Qian Li1,2,3 · Xue Ru2  · Chenyang Li2  · Yaying He2  · Baohui Yang2  · Xuemei Li1,3 · Xuan Zhai2

1 Department of Pediatrics, Women and Children’s Hospital of Chongqing Medical University, Chongqing 401147, China 

2 Department of Neurosurgery, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents’ Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 401122, China 

3 Department of Pediatrics, Chongqing Health Center for Women and Children, Chongqing 400013, China

Abstract

Blood-brain barrier (BBB) disruption is a major driver of neurological deficits after intracerebral hemorrhage (ICH); however, its mechanisms remain unclear. Here, we found that TRIM47 was markedly upregulated after ICH and predominantly expressed in endothelial cells. Endothelial-specific Trim47 deletion normalized peri-hematoma vascular remodeling by reducing the abnormal vascular area and diameter and increasing pericyte coverage, thereby preserving BBB integrity, improving perfusion, reducing neuronal death, and enhancing neurological recovery. Mechanistically, TRIM47 binds to cylindromatosis (CYLD) and promotes its ubiquitination and degradation, leading to activation of NF-κB and P38/JNK-MAPK signaling and neurovascular injury. Endothelial CYLD overexpression reproduced the protective effects of Trim47 deficiency, whereas CYLD knockdown abrogated these effects, confirming that CYLD is a key downstream mediator. Importantly, AAV-mediated Trim47 knockdown restored vascular integrity and improved outcomes after ICH. These findings identify endothelial TRIM47 as a potential therapeutic target for BBB repair and neurovascular recovery.

Keywords

Intracerebral hemorrhage; Blood-brain barrier; TRIM47; CYLD; Endothelial cells

[SpringerLink]