{"entity": "publication", "iuid": "c81c05cd10ed48cf8f9ee510abbbe1ea", "timestamp": "2026-03-16T17:50:04.275Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c81c05cd10ed48cf8f9ee510abbbe1ea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c81c05cd10ed48cf8f9ee510abbbe1ea"}}, "title": "Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity.", "authors": [{"family": "Stokowska", "given": "Anna", "initials": "A"}, {"family": "Aswendt", "given": "Markus", "initials": "M"}, {"family": "Zucha", "given": "Daniel", "initials": "D"}, {"family": "Lohmann", "given": "Stephanie", "initials": "S"}, {"family": "Wieters", "given": "Frederique", "initials": "F"}, {"family": "Mor\u00e1n Suarez", "given": "Javier", "initials": "J"}, {"family": "Atkins", "given": "Alison L", "initials": "AL"}, {"family": "Li", "given": "YiXian", "initials": "Y"}, {"family": "Miteva", "given": "Maria", "initials": "M"}, {"family": "Lewin", "given": "Julia", "initials": "J"}, {"family": "Wiedermann", "given": "Dirk", "initials": "D"}, {"family": "Diedenhofen", "given": "Michael", "initials": "M"}, {"family": "Torinsson Naluai", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Abaffy", "given": "Pavel", "initials": "P"}, {"family": "Valihrach", "given": "Lukas", "initials": "L"}, {"family": "Kubista", "given": "Mikael", "initials": "M"}, {"family": "Hoehn", "given": "Mathias", "initials": "M"}, {"family": "Pekny", "given": "Milos", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}], "type": "journal article", "published": "2023-05-15", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "volume": "133", "issue": "10", "issn-l": "0021-9738"}, "abstract": "Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.", "doi": "10.1172/JCI162253", "pmid": "36995772", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10178843"}, {"db": "pii", "key": "162253"}], "notes": [], "created": "2023-12-01T10:52:07.051Z", "modified": "2023-12-01T10:52:07.054Z"}