仔猪脑出血后的免疫细胞反应及去铁胺和米诺环素的治疗效果

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-06-23 DOI:10.1016/j.expneurol.2025.115354

Qing Xie, Yuxiang Gu, Guohua Xi, Ya Hua, Richard F. Keep, Yingfeng Wan

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引用次数: 0

摘要

背景脑出血（ICH）可诱导免疫细胞浸润。本研究使用仔猪脑叶性脑出血模型来解决三个问题：免疫细胞是否使用血肿内存活或退化的白质进行迁移？某些类型的免疫细胞是否优先迁移到血肿中？去铁胺（DFX）和米诺环素（MINO）这两种潜在的治疗方法如何改变不同免疫细胞向血肿周围区和血肿本身的迁移？方法采用仔猪试验，分为两部分。第一部分，右额叶注射2.5 ml血液，分别于ich后4 h、1、3、7天实施安乐死。第二部分，大鼠ICH后分别给药、DFX或MINO，并于第3天实施安乐死。免疫组化检测血肿和血肿周围B淋巴细胞、T淋巴细胞、中性粒细胞和小胶质细胞/巨噬细胞的分布。结果脑出血后第4 ~ 7天，血肿及血肿周围b淋巴细胞、T淋巴细胞及小胶质细胞/巨噬细胞逐渐增多，中性粒细胞在第4 ~ 1天呈下降趋势，第1 ~ 7天呈上升趋势。所有类型的免疫细胞向血肿核心的浸润在血肿内白质纤维存活的区域更大。与小胶质细胞/巨噬细胞相比，B淋巴细胞和T淋巴细胞更倾向于迁移，这是通过血肿/血肿周围比率来评估的。在ich后第3天，MINO治疗显著降低了B淋巴细胞和T淋巴细胞以及小胶质细胞/巨噬细胞在血肿和血肿周围区域的浸润。DFX诱导了不显著的减少。然而，DFX使血肿和血肿周围的中性粒细胞数量增加，而MINO使中性粒细胞数量减少。结论脑出血可诱导免疫细胞向血肿中心和血肿周围浸润，并与血肿内白质纤维存活有关。DFX和MINO治疗减弱了免疫细胞的反应，尽管DFX增加了中性粒细胞的数量，可能是由于减少了中性粒细胞的凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Immune cell response after intracerebral hemorrhage in piglets and the treatment effects of deferoxamine and minocycline

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Immune cell response after intracerebral hemorrhage in piglets and the treatment effects of deferoxamine and minocycline

Background

Intracerebral hemorrhage (ICH) induces immune cell infiltration. This study used a piglet lobar ICH model to address three questions: do immune cells use surviving or degenerating white matter within hematoma to migrate? Do certain types of immune cell preferentially migrate into the hematoma? How do two potential therapeutics, deferoxamine (DFX) and minocycline (MINO), alter the migration of different immune cells into the perihematomal zone and the hematoma itself?

Methods

This two-part study was conducted in piglets. In the first part, 2.5 ml of blood was injected into the right frontal lobe, and the animals were euthanized at 4 h, days 1, 3 and 7 post-ICH. In the second part, animals were treated with vehicle, DFX or MINO after ICH and euthanized on day 3. Immunohistochemistry was used to examine the distribution of B and T lymphocytes, neutrophils and microglia/macrophages in the hematoma and perihematomal areas.

Results

B and T lymphocytes, as well as microglia/macrophages, gradually increased in the hematoma and peri-hematomal areas from 4 h to day 7 after ICH, while neutrophils decreased from 4 h to day 1 before increasing from day 1 to day 7. The infiltration of all the types of immune cells into the hematoma core was greater in areas with surviving intra-hematoma white matter fibers. There was preferential migration of B and T lymphocytes compared to microglia/macrophages as assessed by the hematoma/perihematomal ratio. MINO treatment significantly reduced infiltration of B and T lymphocytes and microglia/macrophages into the hematoma and peri-hematomal area at day 3 post-ICH. DFX induced a non-significant reduction. However, neutrophil numbers increased in the hematoma and peri-hematomal areas with DFX, while MINO reduced neutrophil numbers.

Conclusions

ICH induces significant infiltration of immune cells infiltration into the hematoma core and perihematomal areas, with this infiltration associated with surviving intra-hematoma white matter fibers. DFX and MINO treatments attenuate the immune cells response, although DFX increase neutrophils number, possible due to reduced neutrophils apoptosis.

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.