Uric Acid Treatment After Stroke Prevents Long-Term Middle Cerebral Artery Remodelling and Attenuates Brain Damage in Spontaneously Hypertensive Rats

AbstractHypertension 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 str ess 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 hypertrophi c 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 normoten...
Source: Translational Stroke Research - Category: Neurology Source Type: research