Intracerebral Hemorrhage-Associated Iron Release Leads to Pericyte-Dependent Cerebral Capillary Function Disruption.

Balk S, Panier F, Brandner S, Coras R, Blümcke I, Ekici AB, Sembill J, Schwab S, Huttner HB, Sprügel M (2025)


Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 15

Journal Issue: 2

DOI: 10.3390/biom15020164

Abstract

Intracerebral hemorrhage leads to immediate brain injury due to local mechanical damage, on which current treatment approaches are focused, but it also induces secondary brain injury. The purpose of this study is to characterize blood components, degradation products and their effects in secondary brain injury. Immunocyto- and immunohistochemistry, Fluorescence-Activated Cell Sorting, WST-1 assays and RNA sequencing were applied using human cell cultures and human ex vivo brain tissue slices. Brain tissue was immediately collected, cooled and sliced during neurosurgical operations to perform experiments on living tissue slices of the human brain. Among the blood degradation products, free iron (Fe2+ and Fe3+), but not hemoglobin, induced detrimental effects on pericyte function and survival (78.5% vs. 94.3%; p-value < 0.001). RNA sequencing revealed ferroptosis as the underlining cellular mechanism, mediated via GPX-4 (log2 fold change > 1.0, p-value < 1.08 × 10-30) in pathway analysis and eventually resulting in oxidative cell death. Pericytes located at cerebral capillary branching sites were specifically affected by ferroptosis, leading to capillary disruption and vasoconstriction, which were partially prevented by ferrostatin-1. Free iron induces the pericyte-dependent disruption of cerebral capillary function and represents a therapeutic target to attenuate secondary injury after intracerebral hemorrhage.

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APA:

Balk, S., Panier, F., Brandner, S., Coras, R., Blümcke, I., Ekici, A.B.,... Sprügel, M. (2025). Intracerebral Hemorrhage-Associated Iron Release Leads to Pericyte-Dependent Cerebral Capillary Function Disruption. Biomolecules, 15(2). https://doi.org/10.3390/biom15020164

MLA:

Balk, Stefanie, et al. "Intracerebral Hemorrhage-Associated Iron Release Leads to Pericyte-Dependent Cerebral Capillary Function Disruption." Biomolecules 15.2 (2025).

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