Abstract

BackgroundIschemic 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.

Highlights

  • Stroke is an important contributor to global mortality and disability burden, with 10.3 million new stroke cases per year [1]

  • We found that Cottonseed oil (CSO) treatment significantly improved neurological deficits, reduced infarction volume, and increased neuronal survival in the ischemic penumbra, suggesting that CSO treatment could be a new strategy for preventing ischemic stroke

  • We found that following Middle cerebral artery occlusion and reperfusion (MCAO-R) injury, the activation of microglia and astrocytes were initiated through Toll-like receptor 4 (TLR4) and Nuclear factor kappa B (NF-κB), respectively

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Summary

Introduction

Stroke is an important contributor to global mortality and disability burden, with 10.3 million new stroke cases per year [1]. Thrombolytic therapy is still the most effective treatment for ischemic stroke, but only a small number of patients receive effective thrombolytic therapy within its narrow therapy time window (4 to 6 h) after stroke onset [2, 3]. Several studies have found that CSO exerts protective effects against peripheral tissue injury such as gastrointestinal disease, principally by reducing inflammatory response [7, 8]. The specific effects and underlying mechanisms by which CSO treatment may alleviate ischemic stroke injury have not been systematically studied. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, CSO is mostly used as a solvent for lipid-soluble drugs. The role of CSO in neuroprotection against stroke has not been previously reported

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