Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte
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.
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Posted 13 Apr, 2020
On 11 Sep, 2020
On 14 Jul, 2020
Received 10 Jul, 2020
On 04 May, 2020
Received 16 Apr, 2020
On 13 Apr, 2020
Invitations sent on 12 Apr, 2020
On 09 Apr, 2020
On 08 Apr, 2020
On 07 Apr, 2020
On 07 Apr, 2020
Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte
Posted 13 Apr, 2020
On 11 Sep, 2020
On 14 Jul, 2020
Received 10 Jul, 2020
On 04 May, 2020
Received 16 Apr, 2020
On 13 Apr, 2020
Invitations sent on 12 Apr, 2020
On 09 Apr, 2020
On 08 Apr, 2020
On 07 Apr, 2020
On 07 Apr, 2020
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