Uric Acid Treatment After Stroke Prevents Long-Term Middle Cerebral Artery Remodelling and Attenuates Brain Damage in Sp
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ORIGINAL ARTICLE
Uric Acid Treatment After Stroke Prevents Long-Term Middle Cerebral Artery Remodelling and Attenuates Brain Damage in Spontaneously Hypertensive Rats Elena Jiménez-Xarrié 1 & Belén Pérez 2 & Ana Paula Dantas 3 & Lídia Puertas-Umbert 2 & Joan Martí-Fabregas 1 & Ángel Chamorro 4,5 & Anna Maria Planas 5,6 & Elisabet Vila 2 & Francesc Jiménez-Altayó 2 Received: 23 May 2018 / Revised: 2 August 2018 / Accepted: 30 August 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract Hypertension is the most important modifiable risk factor for stroke and is associated with poorer post-stroke outcomes. The antioxidant uric acid is protective in experimental normotensive ischaemic stroke. However, it is unknown whether this treatment exerts long-term protection in hypertension. We aimed to evaluate the impact of transient intraluminal middle cerebral artery (MCA) occlusion (90 min)/reperfusion (1–15 days) on brain and vascular damage progression in adult male Wistar-Kyoto (WKY; n = 36) and spontaneously hypertensive (SHR; n = 37) rats treated (i.v./120 min post-occlusion) with uric acid (16 mg kg−1) or vehicle (Locke’s buffer). Ischaemic brain damage was assessed longitudinally with magnetic resonance imaging and properties of MCA from both hemispheres were studied 15 days after stroke. Brain lesions in WKY rats were associated with a transitory increase in circulating IL-18 and cerebrovascular oxidative stress that did not culminate in long-term MCA alterations. In SHR rats, more severe brain damage and poorer neurofunctional outcomes were coupled to higher cortical cerebral blood flow at the onset of reperfusion, a transient increase in oxidative stress and long-lasting stroke-induced MCA hypertrophic remodelling. Thus, stroke promotes larger brain and vascular damage in hypertensive rats that persists for long-time. Uric acid administered during early reperfusion attenuated short- and long-term brain injuries in both normotensive and hypertensive rats, an effect that was associated with abolishment of the acute oxidative stress response and prevention of stroke-induced longlasting MCA remodelling in hypertension. These results suggest that uric acid might be an effective strategy to improve stroke outcomes in hypertensive subjects. Keywords Hypertension . Ischaemia-reperfusion . Ischaemic stroke . Vascular remodelling . Oxidative stress . Antioxidant
Introduction Acute ischaemic stroke is a principal contributor to morbidity and mortality worldwide, and the current trends indicate that
its burden will increase by 2030 [1]. About 90% of the population-attributable risk of stroke is associated with several
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12975-018-0661-8) contains supplementary material, which is available to authorized users. * Francesc Jiménez-Altayó [email protected] 1
2
Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Instituto de Investigación Biomédica (IIB)-Sant Pau, Barcelona
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