Abstract

BackgroundCerebral ischemia and reperfusion (CIR) is a pathological condition characterized by a first blood supply restriction to brain followed by the consequent restoration of blood flow and simultaneous reoxygenation.The aim of this study was to evaluate the neuroprotective effects of Tuscan black kale sprout extract (TBK-SE) bioactivated with myrosinase enzyme, assessing its capability to preserve blood–brain barrier (BBB), in a rat model of CIR.MethodsCIR was induced in rats according to a classic model of carotid artery occlusion for a time period of 1 h and the reperfusion time was prolonged for seven days.ResultsBy immunohistochemical evaluation and western blot analysis of brain and cerebellum tissues, our data have clearly shown that administration of bioactive TBK-SE is able to restore alterations of tight junction components (claudin-5 immunolocalization). Also, bioactive TBK-SE reduces some inflammatory key-markers (p-selectin, GFAP, Iba-1, ERK1/2 and TNF-α), as well as the triggering of neuronal apoptotic death pathway (data about Bax/Bcl-2 balance, p53 and cleaved-caspase 3) and the generation of radicalic species by oxidative stress (results focused on iNOS, nitrotyrosine and Nrf2).ConclusionTaken together, our findings lead to believe that bioactive TBK-SE exerts pharmacological properties in protecting BBB integrity through a mechanism of action that involves a modulation of inflammatory and oxidative pathway as well into control of neuronal death.

Highlights

  • Cerebral ischemia and reperfusion (CIR) is a pathological condition characterized by a first blood supply restriction to brain followed by the consequent restoration of blood flow and simultaneous reoxygenation

  • Treatment of Tuscan black kale sprout extract (TBK-SE) with Myr enzyme catalyzed the quantitative transformation of aliphatic GLs into ITCs, R-sulforaphane being the major one, as already described [20], indole GLs are known to be hydrolysed into highly unstable ITC and are spontaneously transformed to carbinols

  • Bioactive TBK-SE restores blood–brain barrier (BBB) vascular endothelium after CIR induction In order to evaluate whether BBB breakdown is accompanied by the loss or alterations of tight junction (TJ)-associated molecules from the BBB TJs following CIR induction, we investigated the claudin-5 expression by immunohistochemical evaluation

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Summary

Introduction

Cerebral ischemia and reperfusion (CIR) is a pathological condition characterized by a first blood supply restriction to brain followed by the consequent restoration of blood flow and simultaneous reoxygenation. Ready initiation of reperfusion is the most effective treatment for reducing infarct area and behavioural deficits caused by ischemia. Blood flow restoration is causative of additional injury during the cascade of events that characterize and identify the so-called cerebral ischemia/reperfusion (CIR) injury [3]. It is well known that all these events contribute to blood–brain barrier (BBB) breakdown, considered as a critical step in cerebral ischemia pathogenesis [6]. Any abnormality in the structure or function of TJs can lead to BBB dysfunction that may contribute to the development of neurological damage [6]

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