Abstract Details

Title Biofluid Markers of Ischemic Penumbra in Stroke: A Systematic Review and Pathway Analysis

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) P4 - Poster Session 4 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-014

Objective This systematic review aims to assess biomarkers associated with the penumbra in acute ischemic stroke and their underlying molecular pathways.

Background Ischemic penumbra is metabolically active, functionally impaired brain tissue surrounding the infarct core in acute ischemic stroke (AIS). While imaging can identify penumbra via perfusion–diffusion mismatch, access is limited. Biofluid biomarkers may provide a scalable, cost-effective alternative.

Design/Methods A search of Ovid MEDLINE, Embase, PsycINFO, and Web of Science (till September 2023) identified studies involving adults or animal AIS models with imaging-confirmed penumbra, following PRISMA 2020 guidelines. Study quality was assessed using QUADAS-2. Biomarkers were analyzed using STRING (protein–protein interactions) and clusterProfiler (pathway enrichment via Reactome, KEGG, GO).

Results Ten studies (1,293 humans and 8 primates) met inclusion criteria, identifying 51 biomarkers. Four biomarkers demonstrated statistical association with penumbra, interleukin-10 (IL-10; SMD 1.94 [95% CI 0.85–3.03], p = 0.04), mid-regional pro-adrenomedullin (MR-proADM; SMD 0.81 [0.50–1.11], p < 0.001), F2-isoprostanes (F2-isoPs; SMD 0.18 [–0.10–0.48], p = 0.19), and circular OGDH RNA (circOGDH; SMD 0.71 [–0.66–2.07], p = 0.31). 2 of these, IL-10 and MR-proADM were statistically significant. Correlation analyses identified 34 significant genes (e.g., STK26 r = 0.58, p = 0.003; MGA r = 0.58, p = 0.004; IL1B r = –0.59, p = 0.003; NUP98 r = –0.71, p < 0.001) and NT-proBNP (r = 0.199, p < 0.001). Protein–protein network analysis showed IL-1β with highest connectivity (9 interactions), followed by IL-10 (5) and HDAC1/HCAR2 (4). Pathway enrichment revealed positive associations with angiogenesis (FDR < 0.05) and IL-12 signaling, and negative associations with leukocyte migration, chemokine signaling, and platelet activation.

Conclusions IL-10 and MR-proADM were significant penumbra markers, reflecting anti-inflammatory and vasodilatory mechanisms. Markers of leukocyte migration and platelet activation (IL-1β, PF4) were negatively associated. Findings support circulating biomarkers as complementary or alternative tools to imaging for identifying salvageable brain tissue in AIS.

Authors/Disclosures
Amr Elshahat, MD, MBBS (Yale university) PRESENTER	Dr. Elshahat has nothing to disclose.
Yuki Kawamura	Mr. Kawamura has nothing to disclose.
Shubham Misra, PhD (Yale University)	Dr. Misra has nothing to disclose.
Erum Khan, MD	Dr. Khan has nothing to disclose.
Pei Yi Chook	Pei Yi Chook has nothing to disclose.
Ethan Y. Wang (Yale School of Medicine)	Mr. Wang has nothing to disclose.
Priyal Shah (Yale School of Medicine)	No disclosure on file
Mark Reed	Mr. Reed has nothing to disclose.
Melissa Funaro (Yale)	Melissa Funaro has nothing to disclose.
Nishant K. Mishra, MD, MBBS, PhD, FESO (Yale University)	Dr. Mishra has nothing to disclose.

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