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Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte
WeiDong Mi
The First Center of Chinese PLA General Hospital
Corresponding Author
Yulong Ma
The First Center of Chinese PLA General Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0982-9571
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Neuroinflammation.
Background: Ischemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported.
Methods: We treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 hours of reperfusion. Then we measured the neurological scores, infarction volume, neuronal injury and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), NF-κB and C3d, and the presence of A1 type astrocytes and A2 type astrocytes.
Results: We found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood–brain barrier (BBB) disruption and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1β, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells.
Conclusion: Our results first found that CSO treatment alleviated ischemic stroke injury by inhibiting TLR4/NF-κB pathway-mediated microglial and astrocytic activation and inflammation, and by reducing A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.
Keywords
Cottonseed Oil (CSO), Ischemic Stroke, Neuroinflammation, Microglia, Astrocyte, Neuroprotection
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CURRENT STATUS: Published
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Posted 13 Apr, 2020
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On 11 Sep, 2020
No community comments so far
Editorial decision: Major Revision
On 14 Jul, 2020
Review #2 received
Received 10 Jul, 2020
Reviewer #2 agreed
On 04 May, 2020
Review #1 received
Received 16 Apr, 2020
Reviewer #1 agreed
On 13 Apr, 2020
Reviewers invited
Invitations sent on 12 Apr, 2020
Editor invited
On 09 Apr, 2020
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On 08 Apr, 2020
First submitted
On 07 Apr, 2020
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Subject Areas
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This preprint is under consideration at Journal of Neuroinflammation. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte
WeiDong Mi
The First Center of Chinese PLA General Hospital
Corresponding Author
Yulong Ma
The First Center of Chinese PLA General Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0982-9571
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 1
Posted 13 Apr, 2020
Published
On 11 Sep, 2020
No community comments so far
Editorial decision: Major Revision
On 14 Jul, 2020
Review #2 received
Received 10 Jul, 2020
Reviewer #2 agreed
On 04 May, 2020
Review #1 received
Received 16 Apr, 2020
Reviewer #1 agreed
On 13 Apr, 2020
Reviewers invited
Invitations sent on 12 Apr, 2020
Editor invited
On 09 Apr, 2020
Editor assigned
On 08 Apr, 2020
First submitted
On 07 Apr, 2020
Submission checks complete
On 07 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Neuroinflammation.
Background: Ischemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported.
Methods: We treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 hours of reperfusion. Then we measured the neurological scores, infarction volume, neuronal injury and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), NF-κB and C3d, and the presence of A1 type astrocytes and A2 type astrocytes.
Results: We found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood–brain barrier (BBB) disruption and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1β, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells.
Conclusion: Our results first found that CSO treatment alleviated ischemic stroke injury by inhibiting TLR4/NF-κB pathway-mediated microglial and astrocytic activation and inflammation, and by reducing A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8