# Neutrophil extracellular traps and high-precision MRI measures of tissue injury after intracerebral hemorrhage > **NIH NIH K23** · UNIVERSITY OF PENNSYLVANIA · 2024 · $231,255 ## Abstract PROJECT SUMMARY Among stroke subtypes, spontaneous intracerebral hemorrhage (ICH) has the highest mortality and disability. Neutrophilic inflammation is associated with poor outcomes after ICH. However, the mediators of such injury are unknown. Neutrophils are known to secrete neutrophil extracellular traps (NETs). NETs are complexes of DNA and proteins, that neutrophils can secrete into the blood as part of an innate immune response. NETs also facilitate endothelial injury and thrombosis. Previously, NETs have been therapeutically targeted in animal models in other disease entities. In ICH, edema formation through endothelial disruption and ischemic lesions through microthrombosis are prime candidates for NET-mediated tissue injury. Both are associated with poor outcomes. However, the contribution of NETs to edema and ischemic events after ICH has not been investigated. This proposal seeks to biochemically measure markers of harmful neutrophil inflammation (NETs), transendothelial tissue migration (soluble intercellular adhesion molecule 1, sICAM-1), and resulting neuronal injury (neurofilament lightchain, NfL) in blood and cerebrospinal fluid of patients with ICH, and assess local tissue injury (perihemorrhagic edema, PHE volumes), and remote tissue injury (new ischemic lesions) using an innovative MRI approach with high spatial resolution and short imaging time. The proposed research will demonstrate 1) a contribution of NETs to PHE and new ischemic lesions, framed by increased neutrophil tissue infiltration and resulting neuronal death, and will thereby shed light on this mechanism of neutrophil tissue injury in ICH, and identify potential treatment targets to prevent secondary injury after ICH, and 2) the feasibility of a precise MRI sequence that will make PHE measurements a usable study endpoint in future ICH treatment trials. This proposal will allow the candidate to transition to independence with expertise in biomarker validation, clinical trial conduct, and implementation of MRI markers as study endpoints in hemorrhagic stroke studies. The acquired expertise through this proposal will allow the candidate to prospectively study new therapies for ICH using tissue-based definitions of therapeutic success in addition to conventional outcome measures. The candidate has the support of an interdisciplinary team led by the co-primary mentors (1) Dr. Ramon Diaz- Arrastia, an expert in the field of molecular and imaging biomarkers in neurological disease, and (2) Dr. Scott Kasner, an internationally distinguished stroke trialist. The committed collaborators will provide expertise in the use of novel MRI measures as study endpoints in studies on ICH (neuroimaging acquisition, analysis, and interpretation). All mentors and collaborators are committed to the success of the proposed research and to guiding the candidate in becoming an independent clinician-scientist and expert in the field of secondary injury with the long-term goal to find therapie... ## Key facts - **NIH application ID:** 10808669 - **Project number:** 1K23NS131588-01A1 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** Jens Julian Witsch - **Activity code:** K23 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $231,255 - **Award type:** 1 - **Project period:** 2024-03-01 → 2025-02-28 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10808669 ## Citation > US National Institutes of Health, RePORTER application 10808669, Neutrophil extracellular traps and high-precision MRI measures of tissue injury after intracerebral hemorrhage (1K23NS131588-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10808669. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*