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阐明创伤性脑损伤的神经免疫学:揭示细胞间通讯与功能的方法学途径

Elucidating the neuroimmunology of traumatic brain injury: methodological approaches to unravel intercellular communication and function.

作者信息

Abou-El-Hassan Hadi, Bernstock Joshua D, Chalif Joshua I, Yahya Taha, Rezende Rafael M, Weiner Howard L, Izzy Saef

机构信息

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

出版信息

Front Cell Neurosci. 2023 Dec 13;17:1322325. doi: 10.3389/fncel.2023.1322325. eCollection 2023.

DOI:10.3389/fncel.2023.1322325
PMID:38162004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10756680/
Abstract

The neuroimmunology of traumatic brain injury (TBI) has recently gained recognition as a crucial element in the secondary pathophysiological consequences that occur following neurotrauma. Both immune cells residing within the central nervous system (CNS) and those migrating from the periphery play significant roles in the development of secondary brain injury. However, the precise mechanisms governing communication between innate and adaptive immune cells remain incompletely understood, partly due to a limited utilization of relevant experimental models and techniques. Therefore, in this discussion, we outline current methodologies that can aid in the exploration of TBI neuroimmunology, with a particular emphasis on the interactions between resident neuroglial cells and recruited lymphocytes. These techniques encompass adoptive cell transfer, intra-CNS injection(s), selective cellular depletion, genetic manipulation, molecular neuroimaging, as well as co-culture systems and the utilization of organoid models. By incorporating key elements of both innate and adaptive immunity, these methods facilitate the examination of clinically relevant interactions. In addition to these preclinical approaches, we also detail an emerging avenue of research that seeks to leverage human biofluids. This approach enables the investigation of how resident and infiltrating immune cells modulate neuroglial responses after TBI. Considering the growing significance of neuroinflammation in TBI, the introduction and application of advanced methodologies will be pivotal in advancing translational research in this field.

摘要

创伤性脑损伤(TBI)的神经免疫学最近已被公认为是神经创伤后发生的继发性病理生理后果中的一个关键因素。中枢神经系统(CNS)内的免疫细胞和从外周迁移而来的免疫细胞在继发性脑损伤的发展中都起着重要作用。然而,先天免疫细胞和适应性免疫细胞之间通信的确切机制仍未完全了解,部分原因是相关实验模型和技术的使用有限。因此,在本讨论中,我们概述了有助于探索TBI神经免疫学的当前方法,特别强调驻留神经胶质细胞与募集的淋巴细胞之间的相互作用。这些技术包括过继性细胞转移、中枢神经系统内注射、选择性细胞耗竭、基因操作、分子神经影像学,以及共培养系统和类器官模型的利用。通过纳入先天免疫和适应性免疫的关键要素,这些方法有助于检查临床相关的相互作用。除了这些临床前方法外,我们还详细介绍了一条新兴的研究途径,即利用人类生物流体。这种方法能够研究驻留和浸润的免疫细胞如何在TBI后调节神经胶质反应。鉴于神经炎症在TBI中的重要性日益增加,先进方法的引入和应用对于推动该领域的转化研究至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6da/10756680/264d2a06adef/fncel-17-1322325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6da/10756680/09213fcae0ae/fncel-17-1322325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6da/10756680/264d2a06adef/fncel-17-1322325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6da/10756680/09213fcae0ae/fncel-17-1322325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6da/10756680/264d2a06adef/fncel-17-1322325-g002.jpg

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本文引用的文献

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Vγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males.Vγ1 和 Vγ4 γδ T 细胞在男性创伤性脑损伤的免疫病理学中发挥相反的作用。
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Modeling the Inflammatory Response of Traumatic Brain Injury Using Human Induced Pluripotent Stem Cell Derived Microglia.使用人诱导多能干细胞衍生的小胶质细胞对创伤性脑损伤的炎症反应进行建模。
J Neurotrauma. 2023 Oct;40(19-20):2164-2173. doi: 10.1089/neu.2022.0508. Epub 2023 Jul 25.
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B cell treatment promotes a neuroprotective microenvironment after traumatic brain injury through reciprocal immunomodulation with infiltrating peripheral myeloid cells.
B 细胞治疗通过与浸润的外周髓样细胞的相互免疫调节促进创伤性脑损伤后的神经保护微环境。
J Neuroinflammation. 2023 May 31;20(1):133. doi: 10.1186/s12974-023-02812-y.
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Intravital Imaging of Fluorescent Protein Expression in Mice with a Closed-Skull Traumatic Brain Injury and Cranial Window Using a Two-Photon Microscope.利用双光子显微镜对闭合性颅脑损伤和颅窗小鼠的荧光蛋白表达进行活体成像。
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Brain injury accelerates the onset of a reversible age-related microglial phenotype associated with inflammatory neurodegeneration.脑损伤加速了与炎症性神经退行性变相关的可逆转年龄相关小胶质细胞表型的出现。
Sci Adv. 2023 Mar 10;9(10):eadd1101. doi: 10.1126/sciadv.add1101. Epub 2023 Mar 8.
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B cell depletion therapies in autoimmune diseases: Monoclonal antibodies or chimeric antigen receptor-based therapy?自身免疫性疾病中的 B 细胞耗竭疗法:单克隆抗体还是嵌合抗原受体疗法?
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3D In Vitro Blood-Brain-Barrier Model for Investigating Barrier Insults.用于研究血脑屏障损伤的 3D 体外血脑屏障模型
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