2. Academic Validation
  3. Sunitinib attenuates secondary injury via the regulation of peri-hematomal microglia at the acute phase of intracerebral hemorrhage

Sunitinib attenuates secondary injury via the regulation of peri-hematomal microglia at the acute phase of intracerebral hemorrhage

  • Neurotherapeutics. 2025 Dec 11:e00818. doi: 10.1016/j.neurot.2025.e00818.
Yiyong Zeng 1,  Jinhan Cai 2,  Meilin Zheng 2,  Yujie Jiang 3,  Jingyang Le 2,  Shengjun Zhou 4,  Xiang Gao 4,  Chenhui Zhou 5,  Wei Cui 6
Affiliations

Affiliations

  • 1 Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, China; Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology, Shanghai, 200093, China.
  • 2 Translational Medicine Center of Pain, Emotion and Cognition, Health Science Center, Ningbo University, Ningbo, 315211, China.
  • 3 Department of Medical Engineering, Army Medical University Second Affiliated Hospital, Chongqing, 400030, China.
  • 4 Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, China.
  • 5 Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, China. Electronic address: [email protected].
  • 6 Translational Medicine Center of Pain, Emotion and Cognition, Health Science Center, Ningbo University, Ningbo, 315211, China. Electronic address: [email protected].
PMID: 41387160 DOI: 10.1016/j.neurot.2025.e00818
Abstract

Intracerebral hemorrhage (ICH) is a highly fatal stroke subtype with limited treatment options, where pathological activation of peri-hematomal microglia drives acute secondary injury. Colony-stimulating factor 1 receptor (CSF-1R), highly expressed in microglia, is a potential therapeutic target. This study evaluated the effects of short-term administration of sunitinib, a clinically used CSF-1R inhibitor, in a collagenase-induced mouse ICH model and an in vitro Hemoglobin (Hb)-treated BV2 microglial model. Sunitinib significantly improved motor functions, reduced myelin damage, and attenuated microglial activation and neuroinflammation in peri-hematomal tissue. RNA Sequencing revealed that sunitinib might modulate lipid metabolism, phagocytosis, and immune response. In BV2 cells, sunitinib inhibited Hb-induced lipid droplet accumulation, phagocytic reduction, and pro-inflammatory cytokine production, effects mirrored by CSF-1R knockdown. These findings suggest that sunitinib alleviates acute ICH injury by modulating microglial functions, likely through inhibition of the CSF-1R axis, supporting its potential repurposing for central nervous system disorders like ICH.

Keywords

CSF-1R; Intracerebral hemorrhage; Microglia; Neuroinflammation; Phagocytosis; Sunitinib.

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