{"title":"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。","authors":"Lingxin Cai, Jiayin Zhou, Xinran Cao, Huaping Huang, Qin Xie, Haifeng Chu, Gao Chen, Lulu Jin, Zhengwei Mao, Feng Yan","doi":"10.7150/thno.119474","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8897-8915"},"PeriodicalIF":13.3000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439264/pdf/","citationCount":"0","resultStr":"{\"title\":\"Nociceptive Neurons Promote Myeloid-Derived Suppressor Cell Mobilization to Alleviate Post-Stroke Neuroinflammation.\",\"authors\":\"Lingxin Cai, Jiayin Zhou, Xinran Cao, Huaping Huang, Qin Xie, Haifeng Chu, Gao Chen, Lulu Jin, Zhengwei Mao, Feng Yan\",\"doi\":\"10.7150/thno.119474\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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.</p>\",\"PeriodicalId\":22932,\"journal\":{\"name\":\"Theranostics\",\"volume\":\"15 17\",\"pages\":\"8897-8915\"},\"PeriodicalIF\":13.3000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439264/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Theranostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/thno.119474\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.119474","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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.
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.