ECgo: All-optical induction of single endothelial cell injury and capillary occlusion in the brain
Abstract
The ability to induce endothelial cell (EC) damage in the mouse brain with high spatial precision is invaluable for mechanistic studies of brain capillary injury and repair. Here, we introduce an optical method, termed Endothelial Cell guided obliteration (ECgo), that utilizes a two-photon-excitable porphyrin-based photosensitizer ( Ps2P ) to selectively obliterate single ECs within the brain microvascular network. Using the developed approach, we were able to induce occlusions of single capillaries with high spatiotemporal control, while preserving the surrounding tissue. Combined with longitudinal two-photon imaging, ECgo enables studies of morphological and functional consequences of targeted single capillary EC injury in vivo under healthy and diseased conditions.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Jacqueline Condrau
Institute of Pharmacology and Toxicology, University of Zurich
Srinivasa R. Allu
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania
Tatiana V. Esipova
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania
Eva Erlebach
Institute of Pharmacology and Toxicology, University of Zurich
Matthias T. Wyss
Institute of Pharmacology and Toxicology, University of Zurich
Chaim Glück
Institute of Pharmacology and Toxicology, University of Zurich
Luca Ravotto
Institute of Pharmacology and Toxicology, University of Zurich
Thomas Troxler
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania
Mikhail Drobizhev
Department of Microbiology and Cell Biology, Montana State University
Marco Villa
Department of Chemistry “G. Ciamician”, University of Bologna, Via Piero Gobetti 85, 40129 Bologna, Italy
Paola Ceroni
Dipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum− Universit̀a di Bologna, Via Selmi 2, 40126 Bologna, Italy
Mohamad El Amki
Neuroscience Center Zurich, University and ETH Zurich
Sergei A. Vinogradov
Department of Biochemistry and Biophysics, University of Pennsylvania
Bruno Weber
Institute of Pharmacology and Toxicology, University of Zurich