Related Experiment Video
Updated: Dec 21, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
TSPO ligand Ro5-4864 modulates microglia/macrophages polarization after subarachnoid hemorrhage in mice
Jian Zhou1, Xianhui Zhang2, Jianhua Peng3
1Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
Abstract:
Brain injury after subarachnoid hemorrhage (SAH) is closely related to microglia/macrophages-induced neuroinflammation. Translocator protein (TSPO) is a hall marker of activated microglia/macrophages, and the TSPO ligands have been proved to be beneficial for controlling neuroinflammation. Ro5-4864, one of the TSPO ligands, has been reported to be able to regulate inflammation in neurological diseases. Here, we investigated the effects of Ro5-4864 on microglia/macrophages polarization in a SAH mice model, which was induced by endovascular perforation. Ro5-4864 was administered intraperitoneally dissolved in DMSO-saline. Post-SAH assessments included neurological tests, SAH grade, western blotting, ELISA assay and immunohistochemistry. The results showed that brain injury was accompanied by the accumulation of TNF-α and IL-1β, as well as the increase of iNOS protein levels. Finally, we found that Ro5-4864 improved neurological function, increased the expression of anti-inflammatory factors, and influenced phenotypes of M2 microglia/macrophages after SAH. Together, these data reveal a protective role of TSPO ligand Ro5-4864 in inflammatory processes of SAH as well as a potential alternative for SAH treatment.
Insights
Subarachnoid hemorrhage (SAH) brain injury involves neuroinflammation. The translocator protein (TSPO) ligand, Ro5-4864, mitigated this inflammation by modulating microglia/macrophages, offering a potential SAH treatment.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Brain injury following subarachnoid hemorrhage (SAH) is significantly driven by neuroinflammation mediated by microglia/macrophages.
- Translocator protein (TSPO) serves as a key marker for activated microglia/macrophages, and its ligands demonstrate therapeutic potential in neurological conditions.
Purpose of the Study:
- To investigate the therapeutic effects of the TSPO ligand Ro5-4864 on microglia/macrophages polarization in a mouse model of SAH.
- To evaluate the impact of Ro5-4864 on neuroinflammation and neurological deficits post-SAH.
Main Methods:
- SAH was induced in mice via endovascular perforation.
- Ro5-4864 was administered intraperitoneally.
- Neurological function, SAH severity, and inflammatory markers (TNF-α, IL-1β, iNOS) were assessed using neurological tests, western blotting, ELISA, and immunohistochemistry.
Main Results:
- SAH led to increased levels of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS.
- Ro5-4864 administration improved neurological function after SAH.
- Treatment with Ro5-4864 promoted the M2 microglia/macrophage phenotype and increased anti-inflammatory factor expression.
Conclusions:
- The TSPO ligand Ro5-4864 demonstrates a protective role in mitigating neuroinflammation associated with SAH.
- Ro5-4864 shows promise as a potential therapeutic agent for treating subarachnoid hemorrhage by modulating microglia/macrophage responses.
