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抗菌免疫阻碍脑损伤后中枢神经系统血管的修复
作者:小柯机器人 发布时间:2021/9/26 14:39:31

近日,美国国立卫生研究院Dorian B. McGavern及其研究小组发现,抗菌免疫阻碍脑损伤后中枢神经系统血管的修复。这一研究成果于2021年9月23日在线发表在国际学术期刊《自然—免疫学》上。

研究人员证明了全身性注射的微生物和微生物产物以I型干扰素(IFN-I)依赖的方式干扰了创伤性脑损伤(TBI)后的脑膜血管修复,连续的感染会促进慢性失修。从机制上讲,研究人员发现,TBI后沙粒病毒通过诱导IFN-I信号破坏了促进血管生成的骨髓细胞编程。全身性病毒感染同样阻断了颅内出血后脑实质的恢复性血管生成,导致慢性IFN-I信号传导、血脑屏障渗漏和认知-运动功能无法恢复。

这些研究结果揭示了一个共同的免疫机制:系统性感染使中枢神经系统损伤后的修复程序发生偏差,并提供了一个新的治疗靶标来改善恢复。

据介绍,TBI和脑血管损伤是全世界残疾和死亡的主要原因。全身感染常常伴随着这些疾病,并会使结果恶化。脑损伤后的恢复取决于先天性免疫力,但感染对这一过程的影响还不太清楚。

附:英文原文

Title: Antimicrobial immunity impedes CNS vascular repair following brain injury

Author: Mastorakos, Panagiotis, Russo, Matthew V., Zhou, Tianzan, Johnson, Kory, McGavern, Dorian B.

Issue&Volume: 2021-09-23

Abstract: Traumatic brain injury (TBI) and cerebrovascular injury are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders and can worsen outcomes. Recovery after brain injury depends on innate immunity, but the effect of infections on this process is not well understood. Here, we demonstrate that systemically introduced microorganisms and microbial products interfered with meningeal vascular repair after TBI in a type I interferon (IFN-I)-dependent manner, with sequential infections promoting chronic disrepair. Mechanistically, we discovered that MDA5-dependent detection of an arenavirus encountered after TBI disrupted pro-angiogenic myeloid cell programming via induction of IFN-I signaling. Systemic viral infection similarly blocked restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic IFN-I signaling, blood–brain barrier leakage and a failure to restore cognitive–motor function. Our findings reveal a common immunological mechanism by which systemic infections deviate reparative programming after central nervous system injury and offer a new therapeutic target to improve recovery.

DOI: 10.1038/s41590-021-01012-1

Source: https://www.nature.com/articles/s41590-021-01012-1

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex