Abstract WP236: The Gut Microbiome Is Associated With Early Brain Injury After Experimental Subarachnoid Hemorrhage Via Regulation Of Neutrophils
Abstract WP236: The Gut Microbiome Is Associated With Early Brain Injury After Experimental Subarachnoid Hemorrhage Via Regulation Of Neutrophils
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摘要 WP236：肠道微生物群通过调节中性粒细胞与实验性蛛网膜下腔出血后的早期脑损伤相关
DOI：
10.1161/str.53.suppl_1.wp236
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发表时间：
2022
期刊：
影响因子：
8.3
通讯作者：
Kishima Haruhiko
中科院分区：
文献类型：
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作者：
Kawabata Shuhei;Takagaki Masatoshi;Nakamura Hajime;Nishida Takeo;Izutsu Nobuyuki;Takenaka Tomofumi;Matsui Yuichi;Yamada Shuhei;Terada Eisaku;Nakagawa Ryota;Kishima Haruhiko
背景：众所周知，早期脑损伤（EBI），发生在蛛网膜下腔出血（SAH）发作后早期，在很大程度上决定了SAH的预后;然而，尚未开发出有效的EBI治疗方法。包括缺血性中风在内的各种疾病的结果受到肠道微生物组（GM）组成的影响，我们之前已经证明GM也与脑动脉瘤破裂有关。在这里，我们研究了是否事先改变GM可以防止EBI后SAH.Methods：我们改变了GM的7周龄雄性大鼠给予含抗生素的水2周或进行粪便微生物组移植后抗生素治疗。使用16 S rRNA分析GM的组成。蛛网膜下腔注血诱导SAH模型。我们评估了EBI指标，如神经功能评分、脑含水量、伊文思蓝外渗和神经元凋亡。我们还研究了炎性细胞，免疫组化，免疫细胞化学，定量PCR和流式cytometer.Results：有显着差异α和β多样性之间的控制和药物治疗的大鼠。与对照组相比，治疗组大鼠的神经症状、脑水肿、血脑屏障破坏和细胞凋亡明显减少。在炎性细胞中，嗜中性粒细胞浸润到大脑中显着减少在阿尔茨海默氏症治疗的大鼠。有趣的是，SAH后立即观察到对中性粒细胞浸润的预防作用。然后，检查各组在SAH发作前的免疫状态。循环中性粒细胞计数没有差异，但流式细胞术显示老年中性粒细胞显着减少，表现出高反应性表型的抗血小板治疗的大鼠。最后，抗生素对EBI的神经保护作用消失时，GM是onized.Conclusions：我们的研究结果表明，GM影响SAH后EBI的严重性，通过调节中性粒细胞。在未来，调整GM以预防EBI可能成为脑动脉瘤随访患者的新策略。
Background:It is known that early brain injury (EBI), which occurs early after the onset of subarachnoid hemorrhage (SAH), largely determines the prognosis of SAH; however, an effective treatment for EBI has not been developed. The outcome of various diseases including ischemic stroke is influenced by the composition of the gut microbiome (GM) and we have previously shown that the GM is also associated with the rupture of cerebral aneurysms. Here, we studied whether prior alteration of the GM can prevent EBI after SAH.Methods:We altered the GM of 7-week-old male rats by administering antibiotics-containing water for 2 weeks or performing fecal microbiome transplantation after antibiotics treatment. The composition of the GM was profiled using 16S rRNA. SAH was induced by injection of blood in the subarachnoid space of control rats and rats with altered GM. We evaluated EBI indicators such as the neurological score, brain water content, Evans blue extravasation, and neuronal apoptosis. We also studied inflammatory cells using immunohistochemistry, immunocytochemistry, quantitative PCR and flow cytometry.Results:There were significant differences in alpha and beta diversity between the control and antibiotics-treated rats. Compared with the control rats, the antibiotics-treated rats had significantly reduced neurological symptoms, brain edema, blood-brain barrier disruption and apoptosis. Among inflammatory cells, neutrophil infiltration into the brain was significantly reduced in the antibiotics-treated rats. Interestingly, the preventive effect on neutrophil infiltration was already observed immediately after SAH. Next, the immune status of each group before SAH onset was examined. There was no difference in circulating neutrophil counts, but flow cytometry showed a significant decrease in aged neutrophils which exhibit a highly reactive phenotype in the antibiotics-treated rats. Finally, the neuroprotective effect of antibiotics against EBI disappeared when the GM was recolonized.Conclusions:Our findings suggest that the GM affects the severity of EBI after SAH by regulating neutrophils. In the future, adjustment of the GM to prevent EBI may become a new strategy in patients who are being followed for cerebral aneurysms.