Development and Evaluation of a Novel Mouse Model of Asphyxial Cardiac Arrest Revealed Severely Impaired Lymphopoiesis After Resuscitation.
Development and Evaluation of a Novel Mouse Model of Asphyxial Cardiac Arrest Revealed Severely Impaired Lymphopoiesis After Resuscitation.
复制标题
一种新型窒息心脏骤停小鼠模型的开发和评价，显示复苏后造血功能严重受损。
DOI：
10.1161/jaha.120.019142
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发表时间：
2021-06
影响因子：
5.4
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Wang W;Li R;Miao W;Evans C;Lu L;Lyu J;Li X;Warner DS;Zhong X;Hoffmann U;Sheng H;Yang W
动物疾病模型是基础心脏骤停（CA）研究的基石。然而，目前的实验模型CA和复苏的小鼠是有限的。在这项研究中，我们的目的是建立一个窒息CA后心肺复苏（CPR）的小鼠模型，并表征窒息CA/CPR后的免疫反应。通过在麻醉下将O2/N2混合气切换到100%N2气体进行机械通气来诱导小鼠中的CA。真实的血压、脑组织氧、脑血流量和ECG的实时测量结果证实窒息和随后的CA。在规定的CA期后，通过静脉内给予肾上腺素和胸部按压使小鼠复苏。我们将年轻的成年小鼠和老年小鼠置于该模型中，发现在CA/CPR后，与假手术小鼠相比，两组小鼠均表现出显著的神经功能缺损。CA后脑部分析证实神经炎症。对年轻成年和老年小鼠外周器官中CA后免疫应答的详细表征表明，在窒息CA/CPR后的亚急性期，免疫系统受到明显抑制，表现为脾脏和胸腺的急剧萎缩以及严重的淋巴细胞减少症。最后，我们的数据显示，CA后全身淋巴细胞减少症分别伴有胸腺和骨髓中T和B淋巴细胞生成受损。在本研究中，我们建立了一个新的验证窒息CA模型的小鼠。使用这个新的模型，我们进一步证明，窒息CA/CPR显着影响神经和免疫系统，并显着损害T和B细胞的淋巴细胞生成。
Animal disease models represent the cornerstone in basic cardiac arrest (CA) research. However, current experimental models of CA and resuscitation in mice are limited. In this study, we aimed to develop a mouse model of asphyxial CA followed by cardiopulmonary resuscitation (CPR), and to characterize the immune response after asphyxial CA/CPR. CA was induced in mice by switching from an O2/N2 mixture to 100% N2 gas for mechanical ventilation under anesthesia. Real‐time measurements of blood pressure, brain tissue oxygen, cerebral blood flow, and ECG confirmed asphyxia and ensuing CA. After a defined CA period, mice were resuscitated with intravenous epinephrine administration and chest compression. We subjected young adult and aged mice to this model, and found that after CA/CPR, mice from both groups exhibited significant neurologic deficits compared with sham mice. Analysis of post‐CA brain confirmed neuroinflammation. Detailed characterization of the post‐CA immune response in the peripheral organs of both young adult and aged mice revealed that at the subacute phase following asphyxial CA/CPR, the immune system was markedly suppressed as manifested by drastic atrophy of the spleen and thymus, and profound lymphopenia. Finally, our data showed that post‐CA systemic lymphopenia was accompanied with impaired T and B lymphopoiesis in the thymus and bone marrow, respectively. In this study, we established a novel validated asphyxial CA model in mice. Using this new model, we further demonstrated that asphyxial CA/CPR markedly affects both the nervous and immune systems, and notably impairs lymphopoiesis of T and B cells.