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Updated: May 31, 2026
A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
Pan-Cell Death Protein Signature as a Novel Diagnostic and Prognostic Biomarker for Intracerebral Hemorrhage
Tianhong Wang1, Wenbiao Huang2, Zhe Li2
1Department of Neurosurgery, Kunming Jinning District People's Hospital, No. 36 Juqiao Road, Kunyang Subdistrict, Kunming 650000, China.
Insights
Researchers identified a blood-based protein signature to diagnose and predict outcomes for intracerebral hemorrhage (ICH). This discovery offers a promising tool for early detection and risk stratification in brain injury patients.
Area of Science:
- Biochemistry
- Neurology
- Biomarker Discovery
Background:
- Intracerebral hemorrhage (ICH) is a leading cause of death and disability.
- Current diagnostic methods for secondary brain injury lack rapid, blood-based biomarkers.
- There is a critical need for accessible tools to assess ICH severity and prognosis.
Purpose of the Study:
- To identify a circulating protein signature indicative of cell death for diagnosing and prognosing ICH.
- To evaluate the diagnostic and prognostic potential of identified protein biomarkers.
- To investigate the role of these proteins in ICH pathology.
Main Methods:
- Prospective enrollment of 60 ICH patients and 60 healthy controls.
- Plasma sample collection and analysis using Olink proteomics.
- Validation of key proteins (TLR4, ALOX15, FTL, BMF) via ELISA and RT-qPCR.
- Correlation analysis with clinical severity and prognosis (hematoma volume, mRS).
- In vivo validation in animal models.
Main Results:
- A panel of 13 apoptosis-related proteins showed significant dysregulation in ICH patients.
- Four proteins (TLR4, ALOX15, FTL, BMF) demonstrated good diagnostic performance (AUCs 0.799-0.835).
- A multiprotein model achieved excellent diagnostic accuracy (AUC = 0.955).
- Biomarker levels correlated with ICH severity and 90-day functional outcomes (mRS).
- TLR4 upregulation in astrocytes was confirmed in animal models.
Conclusions:
- A circulating pan-cell death protein signature shows promise for ICH diagnosis and prognosis.
- These biomarkers offer a potential tool for early risk stratification and therapeutic targeting.
- The findings provide novel insights into the molecular mechanisms of ICH-induced brain injury.
Abstract:
Intracerebral hemorrhage (ICH) remains a major cause of morbidity and mortality, with no rapid blood-based biomarkers available to assess secondary brain injury. This study aimed to identify a circulating pan-cell death protein signature for diagnosing and prognosing ICH. We prospectively enrolled 60 ICH patients and 60 age/sex-matched healthy controls, collecting plasma at defined time points after ICH onset. Using Olink proteomics, we identified 13 apoptosis-related proteins with significant dysregulation. Four key proteins─TLR4, ALOX15, FTL, and BMF─were validated through ELISA and RT-qPCR, showing good diagnostic performance (AUCs 0.799-0.835). A multiprotein logistic model demonstrated excellent diagnostic accuracy (AUC = 0.955). These biomarkers correlated with clinical severity and prognosis, including hematoma volume and a 90-day modified Rankin Scale (mRS). Additionally, animal models confirmed time-dependent upregulation of TLR4 in astrocytes. This pan-cell death protein signature provides valuable insights into ICH pathology and offers a promising tool for early diagnosis, risk stratification, and therapeutic targeting.
