CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral artery occlusion.
CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral artery occlusion.
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DOI：
10.1007/s00216-020-02987-w
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发表时间：
2021-04
影响因子：
4.3
通讯作者：
Lanekoff I
中科院分区：
文献类型：
--
作者：
Mavroudakis L;Stevens SL;Duncan KD;Stenzel-Poore MP;Laskin J;Lanekoff I
缺血性脑卒中是世界范围内致死和致残的主要原因之一。然而，围绕组织损伤的分子机制是复杂的，需要进一步的研究来获得治疗发展所需的见解。通过给予胞嘧啶-鸟嘌呤（CpG）寡脱氧核苷酸的预防性治疗已被证明可提供针对预期缺血性损伤的神经保护。CpG与Toll样受体9（TLR 9）结合，引起炎症反应的初始化，该炎症反应限制了随后中风时可见的缺血性损伤。在这里，我们使用纳米喷雾解吸电喷雾电离（纳米DESI）质谱成像（MSI）来表征大脑中动脉闭塞（MCAO）和再灌注前CpG预处理的分子效应。通过用适当的内标物掺杂纳米DESI溶剂，我们可以研究和比较磷脂酰胆碱（PC）和溶血磷脂酰胆碱（LPC）在脑缺血半球中的分布，尽管碱金属丰度发生了很大变化。我们的研究结果表明，CpG预处理不仅减少了梗死面积，但它也减少PC的降解和积累的LPC物种，这表明减少细胞膜破裂和整体缺血性损伤。我们的研究结果表明，PC降解的分子机制是完整的，尽管CpG预处理，但这些是有限的，由于初始化的炎症反应。本文的在线版本（10.1007/s 00216 -020-02987-w）包含补充材料，可供授权用户使用。
Ischemic stroke is one of the major causes of death and permanent disability in the world. However, the molecular mechanisms surrounding tissue damage are complex and further studies are needed to gain insights necessary for development of treatment. Prophylactic treatment by administration of cytosine-guanine (CpG) oligodeoxynucleotides has been shown to provide neuroprotection against anticipated ischemic injury. CpG binds to Toll-like receptor 9 (TLR9) causing initialization of an inflammatory response that limits visible ischemic damages upon subsequent stroke. Here, we use nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging (MSI) to characterize molecular effects of CpG preconditioning prior to middle cerebral artery occlusion (MCAO) and reperfusion. By doping the nano-DESI solvent with appropriate internal standards, we can study and compare distributions of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in the ischemic hemisphere of the brain despite the large changes in alkali metal abundances. Our results show that CpG preconditioning not only reduces the infarct size but it also decreases the degradation of PC and accumulation of LPC species, which indicates reduced cell membrane breakdown and overall ischemic damage. Our findings show that molecular mechanisms of PC degradation are intact despite CpG preconditioning but that these are limited due to the initialized inflammatory response. The online version of this article (10.1007/s00216-020-02987-w) contains supplementary material, which is available to authorized users.
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影响因子：
3.6
作者：
Irie, Miho;Fujimura, Yoshinori;Yamato, Mayumi;Miura, Daisuke;Wariishi, Hiroyuki
通讯作者：
Wariishi, Hiroyuki
影响因子：
7.4
作者：
Laskin, Julia;Heath, Brandi S.;Roach, Patrick J.;Cazares, Lisa;Semmes, O. John
通讯作者：
Semmes, O. John
DOI：
10.1007/s13361-011-0122-z
发表时间：
2011-06
影响因子：
3.2
作者：
Hankin JA;Farias SE;Barkley RM;Heidenreich K;Frey LC;Hamazaki K;Kim HY;Murphy RC
通讯作者：
Murphy RC
影响因子：
4.2
作者：
Bergman, Hilde-Marlene;Lundin, Erik;Lanekoff, Ingela
通讯作者：
Lanekoff, Ingela
影响因子：
6.9
作者：
Bahjat FR;Alexander West G;Kohama SG;Glynn C;Urbanski HF;Hobbs TR;Earl E;Stevens SL;Stenzel-Poore MP
通讯作者：
Stenzel-Poore MP