{"title":"中性粒细胞作为脑出血治疗靶点的作用","authors":"Alper Fatih Ardic, Nurittin Ardic","doi":"10.1007/s43441-024-00668-9","DOIUrl":null,"url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of Neutrophils as Therapeutic Targets in Intracerebral Hemorrhage.\",\"authors\":\"Alper Fatih Ardic, Nurittin Ardic\",\"doi\":\"10.1007/s43441-024-00668-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge.</p>\",\"PeriodicalId\":23084,\"journal\":{\"name\":\"Therapeutic innovation & regulatory science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic innovation & regulatory science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s43441-024-00668-9\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"MEDICAL INFORMATICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic innovation & regulatory science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s43441-024-00668-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/16 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"MEDICAL INFORMATICS","Score":null,"Total":0}
引用次数: 0
摘要
脑内出血(ICH)是一个重大的健康问题。它是最常见的中风类型之一,大约一半的患者会因此死亡。一半以上的死亡发生在头两天。除了 ICH 大出血后的群体效应外,颅内血管痉挛、微血栓形成和炎症免疫反应等复杂的病理生理机制也会加重脑损伤。常驻免疫细胞(包括小胶质细胞和星形胶质细胞)和循环免疫细胞(包括中性粒细胞、巨噬细胞和淋巴细胞)都参与了炎症过程。由于浸润的免疫细胞分泌有害物质,炎症反应在急性期尤其有害。炎症反应也有益处,尤其是在后期。免疫细胞在病理生理学中的作用使其成为重要的治疗目标。一般的免疫抑制方法和消耗细胞群(如中性粒细胞)或让它们远离病变部位可能不足以防止 ICH 后的不良后果。这很可能是因为它们抑制了抗炎活性和促炎作用。相反,将免疫细胞导向有益亚群似乎是更合理的解决方案。促炎的中性粒细胞 N1 亚群会损害 ICH 周围的组织。相反,N2 亚群与抗炎反应和组织修复有关。研究表明,当中性粒细胞向 N2 亚群极化时,临床预后会得到改善,梗死体积也会缩小。然而,我们仍需要更多的研究。本研究旨在根据现有知识评估中性粒细胞作为免疫治疗靶点在 ICH 中的作用。
Role of Neutrophils as Therapeutic Targets in Intracerebral Hemorrhage.
Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge.
期刊介绍:
Therapeutic Innovation & Regulatory Science (TIRS) is the official scientific journal of DIA that strives to advance medical product discovery, development, regulation, and use through the publication of peer-reviewed original and review articles, commentaries, and letters to the editor across the spectrum of converting biomedical science into practical solutions to advance human health.
The focus areas of the journal are as follows:
Biostatistics
Clinical Trials
Product Development and Innovation
Global Perspectives
Policy
Regulatory Science
Product Safety
Special Populations