title: White Matter Repair After Extracellular Vesicles Administration in an Experimental Animal Model of Subcortical Stroke.
abstract: Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50-100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers. We found that a single administration of EVs improved functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers in an experimental animal model of subcortical stroke. EVs were found in the animals' brain and peripheral organs after euthanasia. White matter integrity was in part restored by EVs administration mediated by molecular repair factors implicated in axonal sprouting, tract connectivity, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery. This novel role for EVs presents a new perspective in the development of biologics for brain repair.
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Otero-Ortega
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Laso-García
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: María Del Carmen
authors.initials: MD
authors.lastname: Gómez-de Frutos
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Rodríguez-Frutos
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pascual-Guerra
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Fuentes
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Exuperio
authors.initials: E
authors.lastname: Díez-Tejedor
authors.affiliation: Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gutiérrez-Fernández
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D063132:Connectome; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000737:chemistry / Q000637:transplantation*; D005786:Gene Expression Regulation; D007275:Injections, Intravenous; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020521:Stroke / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D060225:Tetraspanin 28 / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D066127:White Matter / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; C554797:Cd81 protein, rat; D009419:Nerve Tissue Proteins; C492143:Pdcd6ip protein, rat; D020543:Proteome; D060225:Tetraspanin 28