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<p>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.</p>

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Maraviroc Attenuates Neuronal Apoptosis by Inhibiting CCR5-Mediated Microglial Activation After Subarachnoid Hemorrhage

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • Jiasen Ye,
  • Hangyang Li,
  • Zhenghong Peng,
  • Zuoyue Duan,
  • Qiang Chen,
  • Yong Jiang,
  • Tianqi Tu,
  • Jianhua Peng

摘要

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.