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Inhibition of Colon...
Inhibition of Colony Stimulating Factor 1 Receptor Suppresses Neuroinflammation and Neonatal Hypoxic-Ischemic Brain Injury
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Zhang, B. H. (författare)
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Ran, Y. W. (författare)
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Wu, S. T. (författare)
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Zhang, F. (författare)
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Huang, H. C. (författare)
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- Zhu, Changlian, 1964 (författare)
- Karolinska Institutet,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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Zhang, S. S. (författare)
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Zhang, X. A. (författare)
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(creator_code:org_t)
- 2021-02-18
- 2021
- Engelska.
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12
- Relaterad länk:
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https://www.frontier...
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Hypoxic-ischemic (HI) brain injury is a major cause of neonatal death or lifetime disability without widely accepted effective pharmacological treatments. It has been shown that the survival of microglia requires colony-stimulating factor 1 receptor (CSF1R) signaling and microglia participate in neonatal HI brain injury. We therefore hypothesize that microglia depletion during a HI insult period could reduce immature brain injury. In this study, CD1 mouse pups were treated with a CSF1R inhibitor (PLX3397, 25 mg/kg/daily) or a vehicle from postnatal day 4 to day 11 (P4-11), and over 90% of total brain microglia were deleted at P9. Unilateral hemisphere HI injury was induced at P9 by permanently ligating the left common carotid arteries and exposing the pups to 10% oxygen for 30 min to produce moderate left hemisphere injury. We found that the PLX3397 treatment reduced HI brain injury by 46.4%, as evaluated by the percentage of brain infarction at 48 h after HI. Furthermore, CSF1R inhibition suppressed the infiltration of neutrophils (69.7% reduction, p = 0.038), macrophages (77.4% reduction, p = 0.009), and T cells (72.9% reduction, p = 0.008) to the brain, the production of cytokines and chemokines (such as CCL12, CCL6, CCL21, CCL22, CCL19, IL7, CD14, and WISP-1), and reduced neuronal apoptosis as indicated by active caspase-3 labeled cells at 48 h after HI (615.20 +/- 156.84/mm(2) vs. 1,205.00 +/- 99.15/mm(2), p = 0.013). Our results suggest that CSF1R inhibition suppresses neuroinflammation and neonatal brain injury after acute cerebral hypoxia-ischemia in neonatal mice.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- colony stimulating factor 1 receptor
- PLX3397
- microglia
- neuroinflammation
- neonatal hypoxic-ischemic brain injury
- Neurosciences & Neurology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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