Spatial Analysis of Neural Cell Proteomic Profiles Following Ischemic Stroke in Mice Using High-Plex Digital Spatial Profiling.
Spatial Analysis of Neural Cell Proteomic Profiles Following Ischemic Stroke in Mice Using High-Plex Digital Spatial Profiling.
复制标题
利用高密度数字空间图谱对小鼠缺血性卒中后神经细胞蛋白质组图谱的空间分析。
DOI：
10.1007/s12035-022-03031-x
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发表时间：
2022-12
影响因子：
5.1
通讯作者：
Ford, Byron D.
中科院分区：
文献类型：
--
作者：
Noll, Jessica M.;Augello, Catherine J.;Kurum, Esra;Pan, Liuliu;Pavenko, Anna;Nam, Andy;Ford, Byron D.
在美国，中风被列为第五大死亡原因和成人残疾的主要原因。中风后神经元损伤的进展被认为是神经胶质细胞、神经元和周围细胞外基质的复杂整合，因此潜在的治疗必须针对这些相互作用产生的有害影响。在这项研究中，我们利用纳米弦数字空间分析（DSP）技术检查了缺血性中风后早期发生的空间细胞和神经炎症机制。对雄性 C57bl/6 小鼠进行光血栓性大脑中动脉闭塞 (MCAO)，并在缺血后 3 天处死。根据感兴趣的区域研究同侧半球的空间区别：与对侧半球相比，缺血核心、梗塞周围组织和梗塞周围正常组织（PiNT）。我们证明，利用 DSP 技术，同侧半球启动了独特的空间调节蛋白质组学谱，可以与免疫组织化学标记 FJB、GFAP 和 Iba-1 一致地进行识别。核心边界轮廓证明了神经元死亡、细胞凋亡、自噬、免疫反应性和早期退化蛋白的诱导。最值得注意的是，核心边界导致神经元蛋白 Map2 和 NeuN 的减少；自噬蛋白 BAG3 和 CTSD 增加；小胶质细胞和外周免疫侵袭蛋白 Iba1、CD45、CD11b 和 CD39 增加；神经退行性蛋白 BACE1、APP、淀粉样蛋白 β 1-42、ApoE 和过度磷酸化 tau 蛋白 S-199 的增加。梗死周围区域的星形胶质细胞、免疫反应性、细胞凋亡和神经退行性蛋白质组谱增加，其中 BAG3、GFAP 和过度磷酸化 tau 蛋白 S-199 增加。与对侧皮层相比，PiNT 区域显示出最小的变化，仅 GFAP 增加。在这项研究中，我们表明已知与中风相关的机制，例如细胞凋亡和炎症，发生在缺血后受损大脑的不同空间区域。我们还证明了特定自噬途径的失调可能导致梗塞周围脑组织的神经变性。总而言之，这些数据表明，识别以时空方式发生的缺血后机制可能会为成功治疗中风的治疗干预带来更精确的目标。
Stroke is ranked as the fifth leading cause of death and the leading cause of adult disability in the USA. The progression of neuronal damage after stroke is recognized to be a complex integration of glia, neurons, and the surrounding extracellular matrix, therefore potential treatments must target the detrimental effects created by these interactions. In this study, we examined the spatial cellular and neuroinflammatory mechanisms occurring early after ischemic stroke utilizing Nanostring Digital Spatial Profiling (DSP) technology. Male C57bl/6 mice were subjected to photothrombotic middle cerebral artery occlusion (MCAO) and sacrificed at 3 days post-ischemia. Spatial distinction of the ipsilateral hemisphere was studied according to the regions of interest: the ischemic core, peri-infarct tissues, and peri-infarct normal tissue (PiNT) in comparison to the contralateral hemisphere. We demonstrated that the ipsilateral hemisphere initiates distinct spatial regulatory proteomic profiles with DSP technology that can be identified consistently with the immunohistochemical markers, FJB, GFAP, and Iba-1. The core border profile demonstrated an induction of neuronal death, apoptosis, autophagy, immunoreactivity, and early degenerative proteins. Most notably, the core border resulted in a decrease of the neuronal proteins Map2 and NeuN; an increase in the autophagy proteins BAG3 and CTSD; an increase in the microglial and peripheral immune invasion proteins Iba1, CD45, CD11b, and CD39; and an increase in the neurodegenerative proteins BACE1, APP, amyloid β 1–42, ApoE, and hyperphosphorylated tau protein S-199. The peri-infarct region demonstrated increased astrocytic, immunoreactivity, apoptotic, and neurodegenerative proteomic profiles, with an increase in BAG3, GFAP, and hyperphosphorylated tau protein S-199. The PiNT region displayed minimal changes compared to the contralateral cortex with only an increase in GFAP. In this study, we showed that mechanisms known to be associated with stroke, such as apoptosis and inflammation, occur in distinct spatial domains of the injured brain following ischemia. We also demonstrated the dysregulation of specific autophagic pathways that may lead to neurodegeneration in peri-infarct brain tissues. Taken together, these data suggest that identifying post-ischemic mechanisms occurring in a spatiotemporal manner may lead to more precise targets for successful therapeutic interventions to treat stroke.
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影响因子：
8.3
作者：
Bosetti F;Koenig JI;Ayata C;Back SA;Becker K;Broderick JP;Carmichael ST;Cho S;Cipolla MJ;Corbett D;Corriveau RA;Cramer SC;Ferguson AR;Finklestein SP;Ford BD;Furie KL;Hemmen TM;Iadecola C;Jakeman LB;Janis S;Jauch EC;Johnston KC;Kochanek PM;Kohn H;Lo EH;Lyden PD;Mallard C;McCullough LD;McGavern LM;Meschia JF;Moy CS;Perez-Pinzon MA;Ramadan I;Savitz SI;Schwamm LH;Steinberg GK;Stenzel-Poore MP;Tymianski M;Warach S;Wechsler LR;Zhang JH;Koroshetz W
通讯作者：
Koroshetz W
影响因子：
37.8
作者：
Baek AE;Sutton NR;Petrovic-Djergovic D;Liao H;Ray JJ;Park J;Kanthi Y;Pinsky DJ
通讯作者：
Pinsky DJ
影响因子：
1.6
作者：
Agrawal P;Gupta K;Mishra V;Agrawal S
通讯作者：
Agrawal S
影响因子：
15.9
作者：
Hyman, Matthew C.;Petrovic-Djergovic, Danica;Pinsky, David J.
通讯作者：
Pinsky, David J.
影响因子：
8.3
作者：
Ito, D;Tanaka, K;Fukuuchi, Y
通讯作者：
Fukuuchi, Y