Journal
TRANSLATIONAL STROKE RESEARCH
Volume 11, Issue 6, Pages 1332-1347Publisher
SPRINGER
DOI: 10.1007/s12975-018-0661-8
Keywords
Hypertension; Ischaemia-reperfusion; Ischaemic stroke; Vascular remodelling; Oxidative stress; Antioxidant
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Funding
- Instituto de Salud Carlos III [FIS PI13/0091, RIC RD12/0042/0006, RETICS-INVICTUS-RD16/019] Funding Source: Medline
- Ministerio de Ciencia e Innovación [SAF2014-56111-R] Funding Source: Medline
- Agència de Gestió d'Ajuts Universitaris i de Recerca [2017-SGR-645] Funding Source: Medline
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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 long-lasting MCA remodelling in hypertension. These results suggest that uric acid might be an effective strategy to improve stroke outcomes in hypertensive subjects.
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