Editors' ChoiceStroke

Fortifying the BBB: Border control by increasing regulators

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Science Translational Medicine  28 Jun 2017:
Vol. 9, Issue 396, eaan6726
DOI: 10.1126/scitranslmed.aan6726

Abstract

Treatment with exogenous regulatory T cells fortifies the blood-brain barrier after tissue plasminogen activator therapy in models of acute ischemic stroke.

Reperfusion strategies using recombinant tissue plasminogen activator (tPA) have been shown to improve clinical outcomes after acute ischemic stroke (AIS). Unfortunately, tPA treatment can lead to complications, the most serious being hemorrhagic transformation. Loss of blood-brain barrier (BBB) integrity is associated with excessive inflammation and an increased risk for hemorrhagic transformation. Recent data have shown that regulatory T cells (Tregs) balance the excessive immune response and protect the integrity of the BBB after stroke. In this study, Mao et al. investigated the therapeutic potential of exogenous Treg infusion in combination with tPA.

In AIS patients, the number of circulating Tregs decreased after stroke and began to repopulate one day later. However, after tPA treatment, repopulation was blunted, suggesting that tPA inhibits Treg production. In two different animal models of stroke, a combination treatment of tPA with Tregs decreased infarct volume, inflammatory markers, and BBB disruption, and also improved behavioral responses. In an in vitro model of BBB, the tPA-induced increased permeability following ischemic-like challenge was recovered by Treg exposure.

These findings confirm the importance of Tregs in regulating the BBB and emphasize the beneficial effects of Treg administration after stroke. An interesting next step is to study the role of Tregs in other clinical settings involving reperfusion injury. AIS patients who undergo mechanical thrombectomy (an invasive procedure to recanalize an occluded artery) experience intense reperfusion; therefore, the combined treatment presented here might potentially provide protective effects.

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