Complement inhibition targets a rich-club within the neuroinflammatory network after stroke to improve radiographic and functional outcomes

Following recent advances in post-thrombectomy stroke care, the role of neuroinflammation and neuroprotective strategies in mitigating secondary injury has gained prominence. Yet, while neuroprotection and anti-inflammatory agents have re-emerged in clinical trials, their success has been limited. T...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neuroinflammation 2025-01, Vol.22 (1), p.1-16, Article 1
Main Authors: Zohdy, Youssef M, Garzon-Muvdi, Tomas, Grossberg, Jonathan A, Barrow, Daniel L, Howard, Brian M, Pradilla, Gustavo, Kobeissy, Firas H, Tomlinson, Stephen, Alawieh, Ali M
Format: Article
Language:English
Subjects:
Anopheles
Complement inhibition
Complications and side effects
Drug therapy
Genes
Genetic aspects
Genetic regulation
Health aspects
Inflammation
Ischemia
Network analysis
Rich-club
Social networks
Stroke
Stroke (Disease)
Transcriptomics
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Following recent advances in post-thrombectomy stroke care, the role of neuroinflammation and neuroprotective strategies in mitigating secondary injury has gained prominence. Yet, while neuroprotection and anti-inflammatory agents have re-emerged in clinical trials, their success has been limited. The neuroinflammatory response in cerebral ischemia is robust and multifactorial, complicating therapeutic approaches targeting single pathways. In this study, we aimed to characterize early inflammatory gene dysregulation following ischemic stroke using translational in-silico and in-vivo approaches. Using an in vivo ischemic stroke model, transcriptomic analysis revealed significant dysregulation of inflammatory genes. Graph theory analysis then showed a rich-club organization among stroke-related genes, with highly connected core nodes. The expression levels of the core genes identified within this network significantly explained radiological outcomes, including T2-signal hyperintensity (R  = 0.57, P 
ISSN:1742-2094
1742-2094
DOI:10.1186/s12974-024-03316-z