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

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rui Hong, Chen Xu, Xuyang Wang, Lin Zhang, Heli Cao, Yao Jing, Shiwen Chen
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引用次数: 0

摘要

创伤性脑损伤(TBI)可导致继发性脑损伤,创伤后神经炎症是病情进展的关键指标,也是患者预后的预测指标。然而,针对创伤性脑损伤后神经炎症的有效、循证药物治疗仍然缺乏。在我们的研究中,我们发现使用机械敏感离子通道抑制剂GsMTx4有效地减轻了脑外伤后小鼠的神经元凋亡和神经炎症,从而改善了异常的神经行为。对损伤部位周围组织的转录组学分析表明,细胞外基质(ECM)降解和炎症相关信号通路下调。补充代谢组学分析揭示了代谢特征和治疗后与炎症反应和ECM降解相关的代谢物丰度降低。我们推测GsMTx4可能调节多种蛋白酶,从而破坏ECM降解-神经炎症反馈回路,最终减轻神经炎症驱动的继发性脑损伤的进展。免疫染色和功能分析进一步证实GsMTx4处理保存了ecm相关蛋白。这些发现表明,GsMTx4可能为TBI后继发性损伤的治疗提供了一种有希望的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
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.
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