雄性大鼠脑缺血时免疫细胞通过白细胞介素 4 促进浸润巨噬细胞表达 BDNF

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Xiaobo Li, Yunqian Guan, Danni Chen, Jiyu Li, Wenxiu Yu, Haiqiang Zou, Bochao Liu, Ling Chen, Zhiguo Chen
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引用次数: 0

摘要

我们曾报道,在大鼠dMCAO模型中,浸润的Ly6C+巨噬细胞仅在大脑皮质梗死处表达脑源性神经营养因子(BDNF)。然而,神经元表达的 BDNF 的变化、诱导 Ly6C+ 细胞表达 BDNF 的生态位成分以及这些成分的细胞来源仍不清楚。本研究采用免疫荧光双重染色法在雄性大鼠大脑中动脉远端闭塞(dMCAO)后3、24和48小时的脑切片上标记BDNF和Ly6C,并将BDNF与Ly6C、IL-4R和IL-10R染色。向脑梗塞处注射中和抗IL-4抗体,用酶联免疫吸附法测定脑梗塞亚区的IL-4和BDNF浓度。为了找出IL-4的细胞来源,小胶质细胞、T细胞和神经元的标记物分别与IL-4共染。在某些梗死亚区,卒中后24-48小时内,主要的BDNF表达细胞迅速从NeuN+神经元转移到Ly6C+细胞,Ly6C+/BDNF+细胞大多表达IL-4受体。注射IL-4中和抗体后,BDNF、IL-4蛋白水平和BDNF+/Ly6C+细胞显著下降。该梗死亚区主要表达IL-4的细胞类型也不是神经元,而是免疫细胞,包括小胶质细胞、单核细胞、巨噬细胞和T细胞。神经元在梗死周围区域维持着 BDNF 和 IL-4 的表达。总之,在大鼠 dMCAO 模型的特定脑区,免疫细胞分泌的 IL-4 是 Ly6C+ 细胞表达 BDNF 的主要诱导因子之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Immune Cells Promote BDNF Expression by Infiltrated Macrophages via Interleukin 4 in the Cerebral Ischemia of Male Rats

Immune Cells Promote BDNF Expression by Infiltrated Macrophages via Interleukin 4 in the Cerebral Ischemia of Male Rats

We reported that infiltrated Ly6C+ macrophages express brain-derived neurotrophic factor (BDNF) only at the cerebral cortex infarct in a rat dMCAO model. However, the changein neuron-expressed BDNF, the niche components that induce the Ly6C+ cells to express BDNF, and the cellular sources of these components, remain unclear. In this study, immunofluorescence double staining was performed to label BDNF and Ly6C on brain sections at 3, 24, and 48 h following distal middle cerebral artery occlusion (dMCAO) of male rats, and to stain BDNF with Ly6C, IL-4R, and IL-10R. A neutralizing anti-IL-4 antibody was injected into the infarct, and the IL-4 and BDNF concentrations in the subareas of the infarct were determined using enzyme-linked immunosorbent assay. To find out the cellular sources of IL-4, the markers for microglia, T cells, and neurons were co-stained with IL-4 separately. In certain infarct subareas, the main BDNF-expressing cells shifted quickly from NeuN+ neurons to Ly6C+ cells during 24–48 h post-stroke, and the Ly6C+/BDNF+ cells mostly expressed IL-4 receptor. Following IL-4 neutralizing antibody injection, the BDNF, IL-4 protein levels, and BDNF+/Ly6C+ cells decreased significantly. The main IL-4-expressing cell type in this infarct subarea is not neuron either, but immune cells, including microglia, monocyte, macrophages, and T cells. The neurons, maintained BDNF and IL-4 expression in the peri-infarct area. In conclusion, in a specific cerebral subarea of the rat dMCAO model, IL-4 secreted by immune cells is one of the main inducers for Ly6C+ cells to express BDNF.

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来源期刊
Journal of Neuroscience Research
Journal of Neuroscience Research 医学-神经科学
CiteScore
9.50
自引率
2.40%
发文量
145
审稿时长
1 months
期刊介绍: The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology. The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.
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