Abstract

Background and PurposeIschemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model.MethodsC57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO.ResultsLBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains.ConclusionsSeven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.

Highlights

  • Ischemic stroke is a devastating cerebrovascular event and a leading cause of death worldwide

  • Mice were subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22hour reperfusion upon filament removal

  • The present study suggests that Lycium barbarum polysaccharides (LBP) may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke

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Summary

Introduction

Ischemic stroke is a devastating cerebrovascular event and a leading cause of death worldwide. Interruption of oxygen and glucose supply leads to cell death cascades which result in BBB breakdown and cerebral edema [5]. Increased BBB permeability contributes to vasogenic edema, causing intravascular fluid to move to the surrounding brain parenchyma. This detrimental edema further reduces blood flow supplying the neurons, causing irreversible apoptosis [6,7]. Extensive interactions among these three components become a vicious cycle, which accelerates brain damage. Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model

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