Endothelial EGLN3-PKM2 signaling induces the formation of acute astrocytic barrier to alleviate immune cell infiltration after subarachnoid hemorrhage

作者全名：Duan, Mingxu; Ru, Xufang; Zhou, Jiru; Li, Yuanshu; Guo, Peiwen; Kang, Wenbo; Li, Wenyan; Chen, Zhi; Feng, Hua; Chen, Yujie

作者地址：[Duan, Mingxu; Ru, Xufang; Zhou, Jiru; Li, Yuanshu; Guo, Peiwen; Kang, Wenbo; Li, Wenyan; Chen, Zhi; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, 29 Gaotanyan St, Chongqing 400038, Peoples R China; [Duan, Mingxu; Ru, Xufang; Zhou, Jiru; Li, Yuanshu; Guo, Peiwen; Kang, Wenbo; Li, Wenyan; Chen, Zhi; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, State Key Lab Trauma Burn & Combined Injury, 29 Gaotanyan St, Chongqing 400038, Peoples R China; [Duan, Mingxu; Ru, Xufang; Zhou, Jiru; Li, Yuanshu; Guo, Peiwen; Kang, Wenbo; Li, Wenyan; Chen, Zhi; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Key Lab Intelligent Diag Treatment & Re, Chongqing 400038, Peoples R China; [Duan, Mingxu; Ru, Xufang; Zhou, Jiru; Li, Yuanshu; Guo, Peiwen; Kang, Wenbo; Li, Wenyan; Chen, Zhi; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Clin Res Ctr Neurosurg, Chongqing 400038, Peoples R China; [Zhou, Jiru] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing 400016, Peoples R China

通信作者：Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, 29 Gaotanyan St, Chongqing 400038, Peoples R China.; Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, State Key Lab Trauma Burn & Combined Injury, 29 Gaotanyan St, Chongqing 400038, Peoples R China.; Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Key Lab Intelligent Diag Treatment & Re, Chongqing 400038, Peoples R China.; Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Clin Res Ctr Neurosurg, Chongqing 400038, Peoples R China.

来源：FLUIDS AND BARRIERS OF THE CNS

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001227220200001

JCR分区：Q1

影响因子：5.9

年份：2024

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Subarachnoid hemorrhage; Glial limitans; Blood-brain barrier; Immune cell infiltration; EGLN3

摘要：Background Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood-brain barrier dysfunction and vasogenic brain edema. However, there is a few days between blood-brain barrier dysfunction and vasogenic brain edema. The present study sought to investigate whether this phenomenon is caused by endothelial injury induced by the acute astrocytic barrier, also known as the glial limitans.Methods Bioinformatics analyses of human endothelial cells and astrocytes under hypoxia were performed based on the GEO database. Wild-type, EGLN3 and PKM2 conditional knock-in mice were used to confirm glial limitan formation after SAH. Then, the effect of endothelial EGLN3-PKM2 signaling on temporal and spatial changes in glial limitans was evaluated in both in vivo and in vitro models of SAH.Results The data indicate that in the acute phase after SAH, astrocytes can form a temporary protective barrier, the glia limitans, around blood vessels that helps maintain barrier function and improve neurological prognosis. Molecular docking studies have shown that endothelial cells and astrocytes can promote glial limitans-based protection against early brain injury through EGLN3/PKM2 signaling and further activation of the PKC/ERK/MAPK signaling pathway in astrocytes after SAH.Conclusion Improving the ability to maintain glial limitans may be a new therapeutic strategy for improving the prognosis of SAH patients.

基金机构：National Natural Science Foundation of China

基金资助正文：Not applicable.