VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage

Objective: Perihematomal edema (PHE) is one of the significant secondary cerebral damages, with the blood–brain barrier's integrity playing a pivotal role in its progression. Strengthening tight junction (TJ) proteins enhances blood–brain barrier integrity, yet the complex genetics behind brain...

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Main Authors: Jingjing Chen, Yi Zhong, Xueshun Xie, Guannan Jiang, Lei Bai, Haiying Li, Xiang Li, Ximing Wang, Gang Chen
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-10-01
Series:Brain Hemorrhages
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589238X24000299
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author Jingjing Chen
Yi Zhong
Xueshun Xie
Guannan Jiang
Lei Bai
Haiying Li
Xiang Li
Ximing Wang
Gang Chen
author_facet Jingjing Chen
Yi Zhong
Xueshun Xie
Guannan Jiang
Lei Bai
Haiying Li
Xiang Li
Ximing Wang
Gang Chen
author_sort Jingjing Chen
collection DOAJ
description Objective: Perihematomal edema (PHE) is one of the significant secondary cerebral damages, with the blood–brain barrier's integrity playing a pivotal role in its progression. Strengthening tight junction (TJ) proteins enhances blood–brain barrier integrity, yet the complex genetics behind brain edema remain not fully understood. Our research endeavors to uncover pivotal genes and their roles in brain edema following cerebral hemorrhage, and to investigate potential treatment strategies. Methods: By analyzing intracerebral hemorrhage (ICH) and control samples using the GSE216607 and GSE206971 datasets, we identified differentially expressed genes. Cross-referencing with the KEGG database, we aligned these genes with those related to tight junctions. Extensive enrichment analysis and protein interactions were performed to examine the expression and clinical significance of the identified genes. Our study employed the C57BL/6J mouse ICH model and qRT-PCR for key gene validation. Results: Notably, VASP, HCLS1, MSN, and EZR, critical for tight junctions, showed increased expression post-ICH, emphasizing their significance in BBB upkeep and PHE progression. Drug validation indicated potential therapeutic effects of Testosterone enanthate, SELENIUM, and LY 294002 on tight junction-related genes. Conclusion: This study sheds light on the potential involvement of these genes in brain edema progression post-ICH, offering promising therapeutic targets. Further research is needed for deeper understanding.
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spelling doaj-art-afbc003fbe1640419de338a1d423e8602025-08-20T01:50:45ZengKeAi Communications Co., Ltd.Brain Hemorrhages2589-238X2024-10-015522323210.1016/j.hest.2024.04.002VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhageJingjing Chen0Yi Zhong1Xueshun Xie2Guannan Jiang3Lei Bai4Haiying Li5Xiang Li6Ximing Wang7Gang Chen8Department of Radiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Corresponding authors at: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China (X. Li). Department of Radiology & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China (X. Wang).Department of Radiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Corresponding authors at: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China (X. Li). Department of Radiology & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China (X. Wang).Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, China; Institute of Stroke Research, Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu Province, ChinaObjective: Perihematomal edema (PHE) is one of the significant secondary cerebral damages, with the blood–brain barrier's integrity playing a pivotal role in its progression. Strengthening tight junction (TJ) proteins enhances blood–brain barrier integrity, yet the complex genetics behind brain edema remain not fully understood. Our research endeavors to uncover pivotal genes and their roles in brain edema following cerebral hemorrhage, and to investigate potential treatment strategies. Methods: By analyzing intracerebral hemorrhage (ICH) and control samples using the GSE216607 and GSE206971 datasets, we identified differentially expressed genes. Cross-referencing with the KEGG database, we aligned these genes with those related to tight junctions. Extensive enrichment analysis and protein interactions were performed to examine the expression and clinical significance of the identified genes. Our study employed the C57BL/6J mouse ICH model and qRT-PCR for key gene validation. Results: Notably, VASP, HCLS1, MSN, and EZR, critical for tight junctions, showed increased expression post-ICH, emphasizing their significance in BBB upkeep and PHE progression. Drug validation indicated potential therapeutic effects of Testosterone enanthate, SELENIUM, and LY 294002 on tight junction-related genes. Conclusion: This study sheds light on the potential involvement of these genes in brain edema progression post-ICH, offering promising therapeutic targets. Further research is needed for deeper understanding.http://www.sciencedirect.com/science/article/pii/S2589238X24000299VASPHCLS1MSNEZRIntracerebral hemorrhagePerihematomal edema
spellingShingle Jingjing Chen
Yi Zhong
Xueshun Xie
Guannan Jiang
Lei Bai
Haiying Li
Xiang Li
Ximing Wang
Gang Chen
VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage
Brain Hemorrhages
VASP
HCLS1
MSN
EZR
Intracerebral hemorrhage
Perihematomal edema
title VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage
title_full VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage
title_fullStr VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage
title_full_unstemmed VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage
title_short VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage
title_sort vasp hcls1 msn and ezr key molecular beacons in the pathophysiology of perihematomal edema post intracerebral hemorrhage
topic VASP
HCLS1
MSN
EZR
Intracerebral hemorrhage
Perihematomal edema
url http://www.sciencedirect.com/science/article/pii/S2589238X24000299
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