Nociceptive Neurons Promote Myeloid-Derived Suppressor Cell Mobilization to Alleviate Post-Stroke Neuroinflammation.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI:10.7150/thno.119474
Lingxin Cai, Jiayin Zhou, Xinran Cao, Huaping Huang, Qin Xie, Haifeng Chu, Gao Chen, Lulu Jin, Zhengwei Mao, Feng Yan
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Abstract

Background: Bone marrow serves as a source and reservoir of immune cells and plays a critical role in central nervous system diseases. Nociceptive neurons are widely distributed in the bone marrow, but their post-infarction changes and immunological functions remain largely unexplored. Methods: A mouse model of middle cerebral artery occlusion (MCAO) and human skull bone marrow samples from stroke patients were analyzed. Calcitonin gene-related peptide (CGRP) signaling was manipulated via receptor knockout and targeted nanoparticle delivery. Immune responses were evaluated primarily through flow cytometry, immunofluorescence, and single-cell RNA sequencing. Results: Activation of nociceptive neurons after cerebral infarction promoted myeloid-biased hematopoiesis in the bone marrow and increased infiltration of myeloid cells into brain tissue, resulting in anti-inflammatory and neuroprotective effects. This regulatory mechanism was mediated by CGRP, which enhanced the proliferation and mobilization of downstream myeloid-derived suppressor cells (MDSC), ultimately improving stroke outcomes. To overcome the hypotensive side effects of CGRP, we employed aged neutrophil membrane-coated nanoparticles for its targeted delivery to bone marrow, achieving sustained release and enhanced efficacy. Conclusion: Nociceptive neurons critically modulate post-stroke bone marrow immune responses by releasing CGRP and activating MDSC. Targeted CGRP delivery to bone marrow represents a promising strategy to suppress neuroinflammation and improve neurological recovery after cerebral infarction.

痛觉神经元促进髓源性抑制细胞动员减轻脑卒中后神经炎症。
背景:骨髓是免疫细胞的来源和储存库,在中枢神经系统疾病中起着关键作用。痛觉神经元广泛分布于骨髓中,但其梗死后的变化和免疫功能仍未得到充分研究。方法:建立小鼠大脑中动脉闭塞(MCAO)模型,对脑卒中患者颅骨骨髓标本进行分析。降钙素基因相关肽(CGRP)信号通过受体敲除和靶向纳米颗粒递送来操纵。免疫应答主要通过流式细胞术、免疫荧光和单细胞RNA测序进行评估。结果:脑梗死后痛觉神经元的激活促进骨髓骨髓偏向性造血,增加骨髓细胞向脑组织的浸润,具有抗炎和神经保护作用。这种调节机制是由CGRP介导的,它增强了下游髓源性抑制细胞(MDSC)的增殖和动员,最终改善了脑卒中的预后。为了克服CGRP的降压副作用,我们采用老化的中性粒细胞膜包被纳米颗粒靶向递送到骨髓,实现了持续释放和增强疗效。结论:痛觉神经元通过释放CGRP和激活MDSC对脑卒中后骨髓免疫反应具有重要调节作用。靶向CGRP骨髓递送是脑梗死后抑制神经炎症和改善神经恢复的一种有希望的策略。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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