Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte.

Abstract

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 h 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), nuclear factor kappa B (NF-κB), C3d and S100A10, 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 and S100A10 protein expression.

CONCLUSION:

Our results first found that CSO treatment alleviated ischemic stroke injury by reducing microglial and astrocytic activation and inflammation, which was related to the inhibition of TLR4/NF-κB pathway and the reduction of A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.

• Authors: Min Liu, Zhipeng Xu, Long Wang, Lixia Zhang, Yi Liu, Jiangbei Cao, Qiang Fu, Yanhong Liu, Hao Li, Jingsheng Lou, Wugang Hou, Weidong Mi, Yulong Ma
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 17 Issue 1 Pg. 270 (Sep 11 2020) ISSN: 1742-2094 [Electronic] England
• PMID: 32917229 (Publication Type: Journal Article)

Chemical References

• Cottonseed Oil
• Cytokines
• Neuroprotective Agents

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Cottonseed Oil (pharmacology, therapeutic use)
• Cytokines (metabolism)
• Inflammation (drug therapy, metabolism)
• Ischemic Stroke (drug therapy, metabolism)
• Male
• Microglia (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)