Intrinsic endothelial remodeling drives brain capillary repair

Jacqueline Condrau; Chaim Glück; Matthias T Wyss; Ladina Hösli; Eva Erlebach; Henri S Zanker; Alexandra von Faber-Castell; Luca Ravotto; Gina Eberle; Srinivasa R Allu; Tatiana V Esipova; Thomas Troxler; Jeffrey L Bennett; Marina Herwerth; Susanne Wegener; Aiman S Saab; Sergei A Vinogradov; Mohamad El Amki; Bruno Weber

doi:10.1016/j.neuron.2026.04.020

Intrinsic endothelial remodeling drives brain capillary repair

Neuron. 2026 May 11:S0896-6273(26)00315-6. doi: 10.1016/j.neuron.2026.04.020. Online ahead of print.

Authors

Jacqueline Condrau¹, Chaim Glück¹, Matthias T Wyss¹, Ladina Hösli¹, Eva Erlebach¹, Henri S Zanker¹, Alexandra von Faber-Castell¹, Luca Ravotto¹, Gina Eberle¹, Srinivasa R Allu², Tatiana V Esipova², Thomas Troxler², Jeffrey L Bennett³, Marina Herwerth⁴, Susanne Wegener⁵, Aiman S Saab¹, Sergei A Vinogradov², Mohamad El Amki⁵, Bruno Weber⁶

Affiliations

¹ Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zürich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zürich, Switzerland.
² Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
³ Departments of Neurology and Ophthalmology, Programs in Neuroscience and Immunology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
⁴ Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zürich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zürich, Switzerland; Department of Neurology, University Hospital Zurich, 8091 Zürich, Switzerland.
⁵ Neuroscience Center Zurich, University and ETH Zurich, 8057 Zürich, Switzerland; Department of Neurology, University Hospital Zurich, 8091 Zürich, Switzerland.
⁶ Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zürich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zürich, Switzerland. Electronic address: bweber@pharma.uzh.ch.

PMID: 42119560
DOI: 10.1016/j.neuron.2026.04.020

Abstract

The brain's microvasculature is essential for oxygen and nutrient delivery; however, the mechanisms underlying cerebral capillary repair following injury remain largely elusive. Here, we identify an unrecognized mechanism through which brain capillary endothelial cells (ECs) autonomously promote capillary remodeling. Using longitudinal two-photon imaging in mice, we demonstrate that following focal endothelial injury and selective loss of a single EC, neighboring ECs extend their plasma membranes toward each other, rapidly re-establishing capillary continuity and blood flow within 24-48 h. This repair process engages vascular endothelial growth factor receptor 2 (VEGFR2) signaling but occurs independently of perivascular or glial cell involvement. Finally, we reveal regional differences in repair efficacy, with hippocampal capillaries exhibiting a slower and less-efficient response compared with those in the cortex. These findings reveal an intrinsic mechanism that safeguards microvascular integrity and suggest that regional vulnerabilities in endothelial repair could shape brain resilience to injury and disease.

Keywords: brain endothelium; capillary repair; cerebral microvasculature; endothelial cell death; endothelial remodeling; in vivo two-photon imaging; microstroke; microvascular dynamics; stroke.