Transcranial photobiomodulation mitigates neuroinflammation by suppressing the activation of neurotoxic microglia through inhibition of the cGAS-STING pathway following intracerebral hemorrhage in mice

  • Chin Med J (Engl). 2026 Jun 20;139(12):1846-1858. doi: 10.1097/CM9.0000000000004019.
Yitong Du  1 ,  Song Wang  2 ,  Yuhualei Pan  1 ,  Huixuan Ma  1 ,  Yushang Zhao  1 ,  Zheng Wei  1 ,  Huadong Lu  3 ,  Dan Xie  1  4 ,  Yongbo Zhang  5
Affiliations
  • 1. Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
  • 2. Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
  • 3. State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Opto-Electronics, Shanxi University, Taiyuan, Shanxi 030006, China.
  • 4. The People's Hospital of Wu Hai Inner Mongolia, Wuhai, Inner Mongolia 016000, China.
  • 5. Center for Neurological disorders, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
PMID: 42045151 DOI: 10.1097/CM9.0000000000004019
Abstract

Background: Neuroinflammation driven by microglial activation is a key contributor to secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to determine whether transcranial photobiomodulation (tPBM) modulates microglial activation and improves neurological outcomes following ICH.

Methods: In this study, we used a mouse model of ICH induced by collagenase to investigate the effects of tPBM at three different power levels (25, 50, and 100 mW) on neurological function, hematoma volume, brain edema, and blood-brain barrier (BBB) integrity. We conducted neurobehavioral assessments and analyzed the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway through quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. In addition, we used the STING-specific inhibitor H151 and agonist diABZI to elucidate the role of the cGAS-STING pathway in neuroinflammation.

Results: tPBM treatment significantly improved neurological recovery, with optimal effects observed at 50 mW. This treatment reduced hematoma volume, alleviated brain edema, and preserved BBB integrity. Importantly, tPBM inhibited microglial polarization toward a neurotoxic phenotype by suppressing the activation of the cGAS-STING pathway. The use of H151 resulted in decreased neuronal Apoptosis and inflammatory cytokine expression, whereas diABZI reinstated inflammatory processes, highlighting the detrimental role of cGAS-STING overactivation in ICH.

Conclusions: tPBM effectively mitigates neuroinflammation and enhances functional recovery after ICH by modulating the cGAS-STING signaling pathway and suppressing neurotoxic microglial activation. This study underscores the potential of tPBM as a novel therapeutic intervention for improving outcomes in patients with ICH, warranting further exploration in clinical settings.

Keywords
Blood–brain barrier; Intracerebral hemorrhage; Microglia; Neutrophil; Transcranial photobiomodulation; cGAS-STING.
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