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.
- 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].
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.