Cerebral ischemia initiates an immediate innate immune response in neonates during cardiac surgery.
Cerebral ischemia initiates an immediate innate immune response in neonates during cardiac surgery.
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DOI：
10.1186/1742-2094-10-24
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发表时间：
2013-02-07
影响因子：
9.3
通讯作者：
Prakken BJ
中科院分区：
文献类型：
--
作者：
Algra SO;Groeneveld KM;Schadenberg AW;Haas F;Evens FC;Meerding J;Koenderman L;Jansen NJ;Prakken BJ
脑缺血后的数小时和数天内会发生强烈的炎症反应。然而，人们对人体缺血性损伤后最初几分钟内的立即先天免疫反应知之甚少。我们在心脏手术中使用循环停止来评估这一点。12名诊断为主动脉弓阻塞的新生儿接受了心肺转流心脏手术和约30分钟的深低温停循环（DHCA，代表脑缺血）。DHCA后即刻和术前至术后24小时的不同时间点从上腔静脉（上级）抽取血样。采用流式细胞术检测中性粒细胞和单核细胞计数及表型，多重免疫分析法检测细胞因子IL-1β、IL-6、IL-8、IL-10、TNFα、sVCAM-1和MCP-1的浓度。将结果与同时从动脉插管中抽取的样本进行比较。另外12名新生儿被随机分配接受相同的程序，但连续顺行脑灌注（ACP）。脑缺血（DHCA）后即刻，静脉血中的中性粒细胞和单核细胞计数高于动脉血（P = 0.03和P = 0.02）。这些细胞的表型均呈活化状态（P均<0.01）。最显著的是“非经典”单核细胞亚群的增加（CD 16中间型;动脉6.6% vs.静脉14%; CD 16 + 13% vs. 22%，均P <0.01）。静脉血中IL-6浓度升高，sVCAM-1浓度降低（均P = 0.03）。相反，在ACP组中，所有炎症参数保持稳定。在新生儿中，深低温期间约30分钟的脑缺血激发了立即的先天性免疫应答，尤其是单核细胞区室。这种现象可能为理解中风的炎症反应及其潜在的有害后果提供了重要线索。ClinicalTrial.gov：NCT01032876
A robust inflammatory response occurs in the hours and days following cerebral ischemia. However, little is known about the immediate innate immune response in the first minutes after an ischemic insult in humans. We utilized the use of circulatory arrest during cardiac surgery to assess this. Twelve neonates diagnosed with an aortic arch obstruction underwent cardiac surgery with cardiopulmonary bypass and approximately 30 minutes of deep hypothermic circulatory arrest (DHCA, representing cerebral ischemia). Blood samples were drawn from the vena cava superior immediately after DHCA and at various other time points from preoperatively to 24 hours after surgery. The innate immune response was assessed by neutrophil and monocyte count and phenotype using FACS, and concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, TNFα, sVCAM-1 and MCP-1 were assessed using multiplex immunoassay. Results were compared to a simultaneously drawn sample from the arterial cannula. Twelve other neonates were randomly allocated to undergo the same procedure but with continuous antegrade cerebral perfusion (ACP). Immediately after cerebral ischemia (DHCA), neutrophil and monocyte counts were higher in venous blood than arterial (P = 0.03 and P = 0.02 respectively). The phenotypes of these cells showed an activated state (both P <0.01). Most striking was the increase in the ‘non-classical’ monocyte subpopulations (CD16intermediate; arterial 6.6% vs. venous 14%; CD16+ 13% vs. 22%, both P <0.01). Also, higher IL-6 and lower sVCAM-1 concentrations were found in venous blood (both P = 0.03). In contrast, in the ACP group, all inflammatory parameters remained stable. In neonates, approximately 30 minutes of cerebral ischemia during deep hypothermia elicits an immediate innate immune response, especially of the monocyte compartment. This phenomenon may hold important clues for the understanding of the inflammatory response to stroke and its potentially detrimental consequences. ClinicalTrial.gov: NCT01032876
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影响因子：
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作者：
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通讯作者：
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