Abstract

Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients’ samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH.

Details

Title
MiRNA expression profiling reveals a potential role of microRNA-148b-3p in cerebral vasospasm in subarachnoid hemorrhage
Author
Ryu, Jee-Yeon 1 ; Zhang, Jianing 1 ; Tirado, Selena-Rae 1 ; Dagen, Sarajune 1 ; Frerichs, Kai U. 1 ; Patel, Nirav J. 1 ; Aziz-Sultan, M. Ali 1 ; Brown, Alison 2 ; Rogers-Grazado, Maximilian 2 ; Amr, Sami S. 2 ; Weiss, Scott T. 3 ; Du, Rose 1 

 Harvard Medical School, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
 Mass General Brigham Personalized Medicine, Mass General Brigham, Cambridge, USA (GRID:grid.452687.a) (ISNI:0000 0004 0378 0997) 
 Harvard Medical School, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
Pages
22539
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3110816693
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.