Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke

Year: 2023

Authors: Conti E., Carlini N., Piccardi B., Mascaro ALA., Pavone FS.

Autors Affiliation: CNR, Neurosci Inst, I-56124 Pisa, Italy; European Lab Nonlinear Spect, I-50019 Sesto Fiorentino, Italy; Univ Florence, Neurofarba Dept, I-50139 Florence, Italy; Univ Florence, Dept Phys & Astron, I-50019 Sesto Fiorentino, Italy; CNR, Natl Inst Opt, I-50019 Sesto Fiorentino, Italy; Translat Res Stroke TREES Working Grp, Florence, Italy.

Abstract: Stroke is one of the main causes of death and disability worldwide. Over the past decades, several animal models of focal cerebral ischemia have been developed allowing to investigate pathophysiological mechanisms underlying stroke progression. Despite intense preclinical research efforts, the need for noninvasive mouse models of vascular occlusion targeting the middle cerebral artery yet avoiding mechanical intervention is still pressing. Here, by applying the photothrombotic stroke model to the distal branch of the middle cerebral artery, we developed a novel strategy to induce a targeted occlusion of a large blood vessel in mice. This approach induces unilateral damage encompassing most of the dorsal cortex from the motor up to the visual regions 1 week after stroke. Pronounced limb dystonia one day after the damage is partially recovered after one week. Furthermore, we observe the insurgence of blood vessel leakage and edema formation in the periinfarct area. Finally, this model elicits a notable inflammatory response revealed as a strong increase in astrocyte density and morphologic complexity in the perilesional region of the cortex compared with both other regions of the ipsilesional and contralesional hemispheres, and in sham-operated mice. To conclude, the stroke model we developed induces in mice the light-mediated occlusion of one of the main targets of human ischemic stroke, the middle cerebral artery, free from the limitations of commonly used preclinical models.

Journal/Review: ENEURO

Volume: 10 (2)      Pages from: ENEURO024422202  to: ENEURO024422202

More Information: This research was funded by the Regione Toscana-Bando Ricerca Salute 2018; by Grant 20RSVP for the project NIMBLE: Integrating Novel NeuroImaging Measurements and Circulating Biomarkers for the Prediction of Secondary Injury following Stroke: from Bench to Bedside; by the Fondazione Cassa di Risparmio di Firenze, Grant SIME 2018/1179 id#24055 for the project STROKELAB2BED . Ictus Ischemico Acuto: dal Laboratorio al Letto del Malato. Studio di biomarcatori ematici e di neuroimaging come predittori di edema cerebrale, estensione della lesione ischemica e dell’outcome funzionale; by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme under Grant no. 692943 (BrainBIT) ; and by the Bank Foundation Fondazione Cassa di Risparmio di Firenze Grant Human Brain Optical Mapping. A.L.A.M F.S.P. providing funding for the study.
KeyWords: astrocytes; BBB permeability; clasping test; immunofluorescence; MCA photothrombotic occlusion
DOI: 10.1523/ENEURO.0244-22.2022

Citations: 3
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