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Complement C3a trea...
Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity
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- Stokowska, Anna (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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Aswendt, M. (author)
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Zucha, D. (author)
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- Lohmann, Stephanie (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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Wieters, F. (author)
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- Suarez, Javier Morán (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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- Atkins, Alison L (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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- Li, YiXian (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Miteva, Maria (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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- Lewin, Julia (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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Wiedermann, Dirk (author)
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Diedenhofen, M. (author)
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- Torinsson Naluai, Åsa, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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Abaffy, P. (author)
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Valihrach, L. (author)
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Kubista, M. (author)
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Hoehn, M. (author)
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- Pekny, Milos, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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- Pekna, Marcela, 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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(creator_code:org_t)
- 2023-03-30
- 2023
- English.
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In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:10
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- focal cerebral-ischemia
- spinal sensitization
- corticospinal tract
- functional recovery
- neural plasticity
- microglia
- receptor
- thrombospondin-4
- anaphylatoxin
- transcriptome
- Research & Experimental Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Clini ...
- By the university
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University of Gothenburg