神经胶质细胞对闭合性颅脑损伤的反应具有独特的、时空协调的方式。

Glial cells react to closed head injury in a distinct and spatiotemporally orchestrated manner.

机构信息

Molecular and Translational Neuroscience, Department of Neurology, Ulm University, Ulm, Germany.

Institute of Physiological Chemistry, Ulm University, Ulm, Germany.

出版信息

Sci Rep. 2024 Jan 30;14(1):2441. doi: 10.1038/s41598-024-52337-4.

Abstract

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Acute neuroinflammation is a prominent reaction after TBI and is mostly initiated by brain-resident glial cells such as microglia, NG2-glia and astrocytes. The magnitude of this reaction paves the way for long-lasting consequences such as chronic neurological pathologies, for which therapeutic options remain limited. The neuroinflammatory response to TBI is mostly studied with craniotomy-based animal models that are very robust but also rather artificial. Here, we aimed to analyze the reaction of glial cells in a highly translational but variable closed head injury (CHI) model and were able to correlate the severity of the trauma to the degree of glial response. Furthermore, we could show that the different glial cell types react in a temporally and spatially orchestrated manner in terms of morphological changes, proliferation, and cell numbers in the first 15 days after the lesion. Interestingly, NG2-glia, the only proliferating cells in the healthy brain parenchyma, divided at a rate that was correlated with the size of the injury. Our findings describe the previously uncharacterized posttraumatic response of the major brain glial cell types in CHI in order to gain a detailed understanding of the course of neuroinflammatory events; such knowledge may open novel avenues for future therapeutic approaches in TBI.

摘要

创伤性脑损伤(TBI)是全球范围内导致死亡和残疾的主要原因。急性神经炎症是 TBI 后的一个突出反应,主要由脑驻留的神经胶质细胞如小胶质细胞、NG2 胶质细胞和星形胶质细胞引发。这种反应的程度为慢性神经病理学等长期后果铺平了道路,而治疗选择仍然有限。TBI 的神经炎症反应主要通过基于开颅术的动物模型进行研究,这些模型非常强大,但也相当人为。在这里,我们旨在分析在高度转化但具有变异性的闭合性脑损伤(CHI)模型中神经胶质细胞的反应,并能够将创伤的严重程度与神经胶质反应的程度相关联。此外,我们还能够证明,不同的神经胶质细胞类型在损伤后 15 天内以时间和空间协调的方式在形态变化、增殖和细胞数量方面反应。有趣的是,NG2 胶质细胞是健康脑实质中唯一增殖的细胞,其分裂速度与损伤的大小相关。我们的研究结果描述了 CHI 中主要脑胶质细胞类型的以前未被描述的创伤后反应,以便更详细地了解神经炎症事件的过程;这种知识可能为 TBI 的未来治疗方法开辟新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/10825139/9c5d44844b23/41598_2024_52337_Fig1_HTML.jpg

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