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Complement C3a trea...
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Stokowska, AnnaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
(author)
Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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2023-03-30
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American Society for Clinical Investigation,2023
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/327307
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https://gup.ub.gu.se/publication/327307URI
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https://doi.org/10.1172/jci162253DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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Aswendt, M.
(author)
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Zucha, D.
(author)
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Lohmann, StephanieGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xlohst
(author)
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Wieters, F.
(author)
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Suarez, Javier MoránGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xmorja
(author)
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Atkins, Alison LGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xatkal
(author)
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Li, YiXianGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
(author)
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Miteva, MariaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
(author)
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Lewin, JuliaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
(author)
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Wiedermann, Dirk
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Diedenhofen, M.
(author)
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Torinsson Naluai, Åsa,1968Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine(Swepub:gu)xnalas
(author)
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Abaffy, P.
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Valihrach, L.
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Kubista, M.
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Hoehn, M.
(author)
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Pekny, Milos,1965Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xpekmi
(author)
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Pekna, Marcela,1966Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xpekma
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
(creator_code:org_t)
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In:Journal of Clinical Investigation: American Society for Clinical Investigation133:100021-97381558-8238
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Stokowska, Anna
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Aswendt, M.
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Zucha, D.
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Lohmann, Stephan ...
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Wieters, F.
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Suarez, Javier M ...
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Atkins, Alison L
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Li, YiXian
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Miteva, Maria
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Lewin, Julia
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Wiedermann, Dirk
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Diedenhofen, M.
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Torinsson Naluai ...
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Abaffy, P.
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Valihrach, L.
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Kubista, M.
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Hoehn, M.
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Pekny, Milos, 19 ...
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Pekna, Marcela, ...
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- MEDICAL AND HEALTH SCIENCES
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and Neurosciences
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University of Gothenburg