Rui Hong, Chen Xu, Xuyang Wang, Lin Zhang, Heli Cao, Yao Jing, Shiwen Chen
{"title":"GsMTx4在小鼠创伤性脑损伤急性期通过维持微环境稳态减轻神经炎症并促进功能恢复","authors":"Rui Hong, Chen Xu, Xuyang Wang, Lin Zhang, Heli Cao, Yao Jing, Shiwen Chen","doi":"10.1007/s11064-025-04567-9","DOIUrl":null,"url":null,"abstract":"<div><p>Traumatic brain injury (TBI) can lead to secondary brain damage, with post-traumatic neuroinflammation being a crucial indicator of the condition’s progression and a predictor of patient prognosis. However, effective, evidence-based pharmacotherapy targeting post-TBI neuroinflammation remains lacking. In our study, we show that the use of the mechanosensitive ion channel inhibitor GsMTx4 effectively alleviated neuronal apoptosis and neuroinflammation, thereby ameliorating abnormal neurological behaviors in mice following TBI. Transcriptomic analysis of the tissue surrounding the injury site indicated downregulation of the extracellular matrix(ECM) degradation and inflammation-related signaling pathways. Complementary metabolomic profiling revealed the metabolic signature and a reduced abundance of metabolites associated with inflammatory responses and ECM degradation after treatment. We speculate that GsMTx4 may modulate various proteases, thereby disrupting the ECM degradation–neuroinflammation feedback loop and ultimately attenuating the progression of neuroinflammation-driven secondary brain damage. Immunostaining and functional assays further confirmed that GsMTx4 treatment preserved ECM-related proteins. These findings suggest that GsMTx4 may offer a promising therapeutic approach for the management of secondary damage following TBI.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GsMTx4 Mitigates Neuroinflammation and Promotes Functional Recovery by Maintaining Microenvironmental Homeostasis During the Acute Phase After Traumatic Brain Injury in Mice\",\"authors\":\"Rui Hong, Chen Xu, Xuyang Wang, Lin Zhang, Heli Cao, Yao Jing, Shiwen Chen\",\"doi\":\"10.1007/s11064-025-04567-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Traumatic brain injury (TBI) can lead to secondary brain damage, with post-traumatic neuroinflammation being a crucial indicator of the condition’s progression and a predictor of patient prognosis. However, effective, evidence-based pharmacotherapy targeting post-TBI neuroinflammation remains lacking. In our study, we show that the use of the mechanosensitive ion channel inhibitor GsMTx4 effectively alleviated neuronal apoptosis and neuroinflammation, thereby ameliorating abnormal neurological behaviors in mice following TBI. Transcriptomic analysis of the tissue surrounding the injury site indicated downregulation of the extracellular matrix(ECM) degradation and inflammation-related signaling pathways. Complementary metabolomic profiling revealed the metabolic signature and a reduced abundance of metabolites associated with inflammatory responses and ECM degradation after treatment. We speculate that GsMTx4 may modulate various proteases, thereby disrupting the ECM degradation–neuroinflammation feedback loop and ultimately attenuating the progression of neuroinflammation-driven secondary brain damage. Immunostaining and functional assays further confirmed that GsMTx4 treatment preserved ECM-related proteins. These findings suggest that GsMTx4 may offer a promising therapeutic approach for the management of secondary damage following TBI.</p></div>\",\"PeriodicalId\":719,\"journal\":{\"name\":\"Neurochemical Research\",\"volume\":\"50 5\",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurochemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11064-025-04567-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11064-025-04567-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
GsMTx4 Mitigates Neuroinflammation and Promotes Functional Recovery by Maintaining Microenvironmental Homeostasis During the Acute Phase After Traumatic Brain Injury in Mice
Traumatic brain injury (TBI) can lead to secondary brain damage, with post-traumatic neuroinflammation being a crucial indicator of the condition’s progression and a predictor of patient prognosis. However, effective, evidence-based pharmacotherapy targeting post-TBI neuroinflammation remains lacking. In our study, we show that the use of the mechanosensitive ion channel inhibitor GsMTx4 effectively alleviated neuronal apoptosis and neuroinflammation, thereby ameliorating abnormal neurological behaviors in mice following TBI. Transcriptomic analysis of the tissue surrounding the injury site indicated downregulation of the extracellular matrix(ECM) degradation and inflammation-related signaling pathways. Complementary metabolomic profiling revealed the metabolic signature and a reduced abundance of metabolites associated with inflammatory responses and ECM degradation after treatment. We speculate that GsMTx4 may modulate various proteases, thereby disrupting the ECM degradation–neuroinflammation feedback loop and ultimately attenuating the progression of neuroinflammation-driven secondary brain damage. Immunostaining and functional assays further confirmed that GsMTx4 treatment preserved ECM-related proteins. These findings suggest that GsMTx4 may offer a promising therapeutic approach for the management of secondary damage following TBI.
期刊介绍:
Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.