Exosomes-mediated delivery of miR-27a-3p antagomir alleviates white matter injury by regulating PPARγ/PRDX1/JNK pathway after subarachnoid hemorrhage in rats

  • Exp Neurol. 2026 May:399:115667. doi: 10.1016/j.expneurol.2026.115667.
Zhaosi Zhang  1 ,  Fuming Liang  1 ,  Daochen Wen  1 ,  Hong Chen  1 ,  Nina Gu  1 ,  Zhao Li  1 ,  Lin Wang  1 ,  Yingwen Wang  1 ,  Qiuling Pan  2 ,  Yajun Zhu  1 ,  Dan Xu  1 ,  Xiaochuan Sun  1 ,  Chongjie Cheng  3 ,  Jin Yan  4
Affiliations
  • 1. Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2. Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3. Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
  • 4. Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 41581691 DOI: 10.1016/j.expneurol.2026.115667
Abstract

White matter injury (WMI) is a critical factor contributing to poor neurological outcomes following subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are key regulators of WMI-related pathology and can be delivered via exosomes, yet their mechanisms and therapeutic potential remain largely unexplored. In this study, miRNA Sequencing revealed a significant upregulation of miR-27a-3p in peripheral blood exosomes after SAH, which was further confirmed in white matter tissue. BV2 cell-derived exosomes loaded with miR-27a-3p antagomir were administered intranasally and effectively targeted oligodendrocytes. Treatment with these exosomes alleviated WMI by reducing oligodendrocyte Apoptosis and promoting the proliferation and differentiation of oligodendrocyte precursor cells, leading to improved neurological and electrophysiological recovery. Mechanistically, miR-27a-3p inhibited PPARγ, resulting in downregulation of PRDX1 and activation of the JNK pathway, which triggered oligodendrocyte Apoptosis. These findings demonstrate that exosome-mediated delivery of miR-27a-3p antagomir mitigates SAH-induced WMI through modulation of the PPARγ/PRDX1/JNK axis, providing a promising noninvasive therapeutic approach for enhancing white matter repair and functional recovery after SAH.

Keywords
Exosome; Subarachnoid hemorrhage; White matter injury; miR-27a-3p.
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