Ischemia-reperfusion injury in stroke: impact of the brain barriers and brain immune privilege on neutrophil function.
Ischemia-reperfusion injury in stroke: impact of the brain barriers and brain immune privilege on neutrophil function.
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DOI：
10.1177/1756286418794184
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发表时间：
2018
影响因子：
5.9
通讯作者：
Engelhardt B
中科院分区：
文献类型：
--
作者：
Enzmann G;Kargaran S;Engelhardt B
缺血性卒中后再灌注损伤是一个复杂的病理生理过程，涉及多种机制，从兴奋性氨基酸和离子失衡的释放到诱导细胞凋亡和坏死，再到氧化应激和炎症。中性粒细胞向脑实质的迁移和其丰富的蛋白酶的释放通常被认为是缺血性卒中后神经元细胞死亡和急性再灌注损伤的主要原因。最近在实验和人类中风中的发现挑战了这一观点，因为大多数中性粒细胞被发现在神经血管单位（NVU）和蛛网膜下腔（SAS）内积聚，在那里它们通过胶质界膜与脑实质保持分离。脑实质是免疫特权部位，免疫细胞不易接近，不会引发刻板的适应性或先天性免疫应答。了解大脑免疫特权需要深入了解其独特的解剖结构，其中包括胶质限制素在内的大脑屏障建立了在免疫系统可及性方面显着不同的隔间。我们在这里提出，脑免疫豁免也延伸到缺血性损伤，脑实质不引起中性粒细胞的快速浸润，如在外周器官缺血事件中观察到的。相反，NVU和SAS中的中性粒细胞蓄积可能对中枢神经系统（CNS）的脑脊液（CSF）引流产生潜在影响，从而影响缺血性卒中后的水肿形成和再灌注损伤。将脑免疫豁免的解剖学和功能意义与中性粒细胞在再灌注损伤中的毋庸置疑的作用相结合是利用适当的治疗干预策略以减少缺血性卒中后神经元细胞死亡的先决条件。
Reperfusion injury following ischemic stroke is a complex pathophysiological process involving numerous mechanisms ranging from the release of excitatory amino acids and ion disequilibrium to the induction of apoptosis and necrosis, to oxidative stress and inflammation. The migration of neutrophils into the brain parenchyma and release of their abundant proteases are generally considered the main cause of neuronal cell death and acute reperfusion injury following ischemic stroke. Recent findings in experimental and human stroke have challenged this view, as the majority of neutrophils were rather found to accumulate within the neurovascular unit (NVU) and the subarachnoid space (SAS) where they remain separated from the brain parenchyma by the glia limitans. The brain parenchyma is an immune-privileged site that is not readily accessible to immune cells and does not elicit stereotypic adaptive or innate immune responses. Understanding brain immune privilege requires intimate knowledge of its unique anatomy in which the brain barriers, that include the glia limitans, establish compartments that differ remarkably with regard to their accessibility to the immune system. We here propose that the brain immune privilege also extends to an ischemic insult, where the brain parenchyma does not evoke a rapid infiltration of neutrophils as observed in ischemic events in peripheral organs. Rather, neutrophil accumulation in the NVU and SAS could have a potential impact on cerebrospinal fluid (CSF) drainage from the central nervous system (CNS) and thus on edema formation and reperfusion injury after ischemic stroke. Integrating the anatomical and functional implications of the brain immune privilege with the unquestionable role of neutrophils in reperfusion injury is a prerequisite to exploit appropriate strategies for therapeutic interventions aiming to reduce neuronal cell death after ischemic stroke.
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影响因子：
12.7
作者：
Arbel-Ornath M;Hudry E;Eikermann-Haerter K;Hou S;Gregory JL;Zhao L;Betensky RA;Frosch MP;Greenberg SM;Bacskai BJ
通讯作者：
Bacskai BJ
DOI：
10.1073/pnas.0803945105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Breckwoldt, Michael O.;Chen, John W.;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
影响因子：
4.4
作者：
Doering, Axinia;Wild, Martin;Engelhardt, Britta
通讯作者：
Engelhardt, Britta
影响因子：
3.3
作者：
ANDERSSON, PB;PERRY, VH;GORDON, S
通讯作者：
GORDON, S
DOI：
10.1097/nen.0b013e3181edbc1a
发表时间：
2010-09-01
影响因子：
3.2
作者：
Chinnery, Holly R.;Ruitenberg, Marc J.;McMenamin, Paul G.
通讯作者：
McMenamin, Paul G.