Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion.
Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion.
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DOI：
10.1016/j.expneurol.2017.07.016
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发表时间：
2017-11
影响因子：
5.3
通讯作者：
Halterman MW
中科院分区：
文献类型：
--
作者：
Mai N;Prifti L;Rininger A;Bazarian H;Halterman MW
缺血性神经退行性变仍然是心脏复苏后死亡的主要原因。最近的研究表明，胃肠道缺血与心脏骤停综合征（PCAS）相关的败血症样反应有关。然而，高达86%的复苏患者出现的低级别内毒素血症对脑缺血再灌注损伤的影响程度尚未得到研究。本研究报道，与单纯缺血相比，全脑缺血（GCI）后单次注射低剂量脂多糖（50 μg/kg， IP）可诱导血脑屏障通透性、小胶质细胞激活、皮质损伤和体内功能下降。虽然GCI足以诱导中性粒细胞（PMN）激活并募集到缺血后的中枢神经系统，但微量内毒素血症对全身炎症标志物（包括PMN启动、肺损伤和肺及其他非缺血器官（包括肾和肝）内的PMN负担）表现出协同作用。我们的研究结果预测，针对阻断心脏骤停幸存者血清学隐匿性内毒素血症影响的急性干预措施将限制迟发性神经变性、多器官功能障碍和PCAS的潜在其他特征。这项工作还介绍了肺脑耦合作为一种新的治疗靶点，在先天性免疫启动和心脏骤停及相关脑血管疾病后缺血性神经变性方面具有广泛的作用。
Post-ischemic neurodegeneration remains the principal cause of mortality following cardiac resuscitation. Recent studies have implicated gastrointestinal ischemia in the sepsis-like response associated with the post-cardiac arrest syndrome (PCAS). However, the extent to which the resulting low-grade endotoxemia present in up to 86% of resuscitated patients affects cerebral ischemia-reperfusion injury has not been investigated. Here we report that a single injection of low-dose lipopolysaccharide (50 μg/kg, IP) delivered after global cerebral ischemia (GCI) induces blood-brain barrier permeability, microglial activation, cortical injury, and functional decline in vivo, compared to ischemia alone. And while GCI was sufficient to induce neutrophil (PMN) activation and recruitment to the post-ischemic CNS, minimal endotoxemia exhibited synergistic effects on markers of systemic inflammation including PMN priming, lung damage, and PMN burden within the lung and other non-ischemic organs including the kidney and liver. Our findings predict that acute interventions geared towards blocking the effects of serologically occult endotoxemia in survivors of cardiac arrest will limit delayed neurodegeneration, multi-organ dysfunction and potentially other features of PCAS. This work also introduces lung-brain coupling as a novel therapeutic target with broad effects on innate immune priming and post-ischemic neurodegeneration following cardiac arrest and related cerebrovascular conditions.
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影响因子：
8.2
作者：
Coultrap, Steven J.;Vest, Rebekah S.;Ashpole, Nicole M.;Hudmon, Andy;Bayer, K. Ulrich
通讯作者：
Bayer, K. Ulrich
TRPV1 通道在缺血/再灌注引起的急性肾损伤中的作用。
影响因子：
3.7
作者：
Chen L;Markó L;Kaßmann M;Zhu Y;Wu K;Gollasch M
通讯作者：
Gollasch M
影响因子：
6.5
作者：
Grimaldi, D.;Guivarch, E.;Cariou, A.
通讯作者：
Cariou, A.
影响因子：
--
作者：
Cardiff, Robert D;Miller, Claramae H;Munn, Robert J
通讯作者：
Munn, Robert J
影响因子：
37.8
作者：
Adrie, C;Adib-Conquy, M;Cavaillon, JM
通讯作者：
Cavaillon, JM