Related Experiment Video
Updated: May 21, 2026
Stereotaxic Microinjection of Viral Vectors Expressing Cre Recombinase to Study the Role of Target Genes in Cocaine Conditioned Place Preference
Published on: July 30, 2013
Maraviroc Attenuates Neuronal Apoptosis by Inhibiting CCR5-Mediated Microglial Activation After Subarachnoid
Jiasen Ye1,2, Hangyang Li1,2, Zhenghong Peng2,3
1Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, NO. 25 of Taiping Street, Luzhou, 646000, Sichuan, China.
Abstract:
Subarachnoid hemorrhage (SAH) triggers robust neuroinflammatory responses that contribute to secondary brain injury, with microglia acting as central mediators; however, the upstream regulators governing microglial activation remain incompletely understood. To address this, we investigated the role of C-C chemokine receptor 5 (CCR5) using a murine endovascular perforation SAH model. Expression profiling revealed that CCR5 is rapidly upregulated after SAH, with prominent expression in microglia in the cortex and perilesional region. We then evaluated the therapeutic efficacy of pharmacological inhibition using the intranasal CCR5 antagonist maraviroc (MVC). MVC treatment successfully shifted microglia toward an anti-inflammatory phenotype and reduced pro-inflammatory cytokines. This inflammatory modulation attenuated brain edema, suppressed neuronal apoptosis, and significantly improved both early and long-term neurological outcomes. Furthermore, in vitro experiments confirmed that MVC reverses oxyhemoglobin-induced pro-inflammatory microglial polarization, indirectly protecting neurons from microglia-dependent injury. Collectively, these findings identify CCR5 as an important regulator of microglia-associated neuroinflammation after SAH and suggest that MVC exerts neuroprotection, at least in part, through modulation of the CCR5-related inflammatory microenvironment.
Insights
Targeting C-C chemokine receptor 5 (CCR5) with maraviroc (MVC) reduces neuroinflammation after subarachnoid hemorrhage (SAH). This approach improves brain recovery and neurological outcomes by modulating microglial activation.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Subarachnoid hemorrhage (SAH) causes secondary brain injury via neuroinflammation, with microglia as key mediators.
- Upstream regulators of microglial activation in SAH remain poorly understood.
Purpose of the Study:
- Investigate the role of C-C chemokine receptor 5 (CCR5) in SAH-induced neuroinflammation.
- Evaluate the therapeutic potential of CCR5 inhibition using maraviroc (MVC).
Main Methods:
- Utilized a murine endovascular perforation model of SAH.
- Assessed CCR5 expression in microglia post-SAH.
- Administered intranasal CCR5 antagonist maraviroc (MVC).
- Performed in vitro experiments using oxyhemoglobin-treated microglia.
Main Results:
- CCR5 expression was significantly upregulated in microglia after SAH.
- MVC treatment shifted microglia to an anti-inflammatory phenotype, reducing pro-inflammatory cytokines.
- MVC attenuated brain edema, suppressed neuronal apoptosis, and improved neurological outcomes.
- In vitro, MVC reversed oxyhemoglobin-induced pro-inflammatory microglial polarization.
Conclusions:
- CCR5 is a critical regulator of microglia-driven neuroinflammation following SAH.
- CCR5 inhibition with MVC offers neuroprotection by modulating the inflammatory microenvironment.
- MVC demonstrates therapeutic potential for improving outcomes after subarachnoid hemorrhage.
