无机硝酸盐通过Sialin减轻创伤性脑损伤后的神经炎症

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-05-10 DOI:10.1016/j.tice.2025.102955

Zanxu Liu , Liang Hu , Qiaochu Wang , Xiang Zhao , Weiming Liu , Bin Zhang , Wen Pan , Wenpeng Song , Xi Chen , Chunmei Zhang , Jinsong Wang , Songlin Wang , Jian Zhou

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引用次数: 0

摘要

背景：创伤性脑损伤（TBI）因其严重的后果而成为神经外科的一个重要问题。神经炎症是初始脑损伤后的关键反应，导致累积的神经元损伤和慢性神经变性，有效的治疗方法有限。无机硝酸盐是一种重要的营养物质，以其抗炎特性而闻名，被广泛用于疾病的预防和治疗。本研究考察了无机硝酸盐对神经炎症的短期影响，并探讨了Sialin在tbi后早期神经保护中的作用。方法采用电控皮质冲击器（eCCI）模型对C57BL/6小鼠进行脑外伤治疗。伤后1、3、7天，每日两次灌胃硝酸盐或无菌生理盐水，直至牺牲。评估神经行为功能，并收集脑组织进行形态学、组织病理学和分子分析。结果硝酸酯可促进神经行为功能恢复，改善3 dpi时的神经预后。虽然硝酸盐没有显著减少结构损伤，但它确实减少了TBI早期的神经元损失和凋亡。与对照组相比，3 dpi时损伤大脑的rna测序显示，早期硝酸盐处理后与免疫过程相关的基因和信号通路更多，表明炎症抑制。在mRNA和蛋白水平上进一步证实了这一点。具体而言，与相应的TBI载体组相比，早期硝酸盐显著抑制了炎症介质的关键基因标记。然而，Slc17a5的敲低降低了硝酸盐对TBI小鼠短期神经行为的有效性，并使其抗炎作用无效。结论无机硝酸盐可以改善脑外伤后的神经预后，减轻神经炎症，部分原因是Sialin介导的炎症反应正常化。这一发现为硝酸盐对创伤性脑损伤的保护作用奠定了良好的基础。

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Inorganic nitrate attenuates neuroinflammation after traumatic brain injury via Sialin

Background

Traumatic brain injury (TBI) is a significant concern in neurosurgery due to its severe consequences. Neuroinflammation is a critical response following the initial brain insult, leading to cumulative neuronal damage and chronic neurodegeneration, with limited effective treatments available. Inorganic nitrate, an essential nutrient known for its anti-inflammatory properties, is widely utilized in disease prevention and treatment. This study investigated the short-term effects of inorganic nitrate on neuroinflammation and explored the role of Sialin in neuroprotection during the early phase post-TBI.

Methods

Male C57BL/6 mice underwent TBI using an electrically controlled cortical impactor (eCCI) model. Animals were administered nitrate or sterile saline intragastrically twice daily for 1,3 or 7 days post-injury (dpi) until sacrifice. Neurobehavioral function was evaluated, and brain tissues were collected for morphological, histopathological, and molecular analyses.

Results

Nitrate enhanced neurobehavioral function recovery and improved neurological outcomes at 3 dpi. While nitrate did not significantly reduce structural damage, it did decrease neuronal loss and apoptosis in the early stages of TBI. RNA-seq of injured brains at 3 dpi revealed more genes and signaling pathways linked to immune processes following early nitrate treatment compared to the vehicle, indicating inflammation inhibition. This was further confirmed at the mRNA and protein levels. Specifically, key gene markers of inflammatory mediators were notably suppressed by early nitrate compared to the corresponding TBI vehicle groups. However, the knockdown of Slc17a5 reduced the effectiveness of nitrate on short-term neurobehavior in TBI mice and nullified its anti-inflammatory effects.

Conclusion

Inorganic nitrate can improve neurological outcomes and attenuate neuroinflammation following TBI, attributed in part to the normalisation of the inflammatory response mediated by Sialin. The discovery lays a promising groundwork for the protective effects of nitrate in TBI conditions.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.