2. Academic Validation
  3. Edaravone attenuates cerebral inflammation by inhibiting mast cells degranulation via ROS/STIM1 signaling pathway in HIE model

Edaravone attenuates cerebral inflammation by inhibiting mast cells degranulation via ROS/STIM1 signaling pathway in HIE model

  • Int Immunopharmacol. 2025 Jun 26:159:114880. doi: 10.1016/j.intimp.2025.114880.
Qingqing Ye 1,  Weitian Lu 1,  Tingsong Li 2,  Yuan Li 1,  Shilong Tang 3,  Pengyu Xiao 1,  Ting Wei 1,  Jiayi Zhao 4,  Zhenhua Wang 5,  Juan Huang 6
Affiliations

Affiliations

  • 1 Department of Anatomy, Basic Medical College, Chongqing Medical University, Chongqing, China; Institute of Neuroscience, Basic Medical College, Chongqing Medical University, Chongqing, China; Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing, China.
  • 2 Department of Rehabilitation, Children's Hospital of Chongqing Medical University (CHCMU), Chongqing, China; National Clinical Research Center for Child Health and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
  • 3 National Clinical Research Center for Child Health and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 4 College of Pharmacy, Chongqing Medical University, Chongqing, China.
  • 5 Technical Department of Criminal Investigation Branch, Deyang Police Office, Deyang 618000, China.
  • 6 Department of Anatomy, Basic Medical College, Chongqing Medical University, Chongqing, China; Institute of Neuroscience, Basic Medical College, Chongqing Medical University, Chongqing, China; Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing, China. Electronic address: huangjuan@cqmu.edu.cn.
PMID: 40394799 DOI: 10.1016/j.intimp.2025.114880
Abstract

Mast cells (MCs) degranulation is responsible for the occurrence and development of neuroinflammation after hypoxic-ischemic encephalopathy (HIE). Stromal interaction molecule 1 (STIM1) serves as a CA2+ sensor on the endoplasmic reticulum. It has been demonstrated that the supression of STIM1 impedes degranulation of MCs in numerous prior investigations. This study aimed to explore the impact of edaravone, an oxygen radical scavenger, on MCs degranulation in HIE rat model, and to explore the contribution of Reactive Oxygen Species (ROS)/STIM1 pathway in mediating MCs degranulation. Nine-day old undetermined gender rat pups were experienced hypoxic-ischemic (HI) injury and edaravone was administered intraperitoneally at 10 min after HI insults. CM4620, an inhibitor of STIM1, was administered intraperitoneally at 10 min after HI insults to elucidate the possible mechanisms. TTC staining, Western blot analysis, immunofluorescence staining, brain water content, cerebral blood flow, toluidine blue staining, Nissl staining, and neurobehavioral test were conducted. The results demonstrated that tryptase, STIM1, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were increased after HI, and edaravone significantly improved neurobehavioral outcomes, reduced brain water content, decreased infarct area, reduced the accumulation of ROS, decreased the degranulation of MCs, and downregulated the protein expression of tryptase, STIM1, IL-6 and TNF-α. CM4620 inhibited MCs degranulation and downregulated the expression of STIM1, tryptase, IL-6, TNF-α. In conclusion, the current investigation revealed that edaravone attenuates MCs degranulation and neuroinflammation, at least partially, via ROS/STIM1 pathway after HI injury.

Keywords

Hypoxic-ischemic encephalopathy; Mast cells; Neuroinflammation; ROS; STIM1.

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