Abstract
BackgroundMetabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia. Microvascular dysfunction is an important feature underlying the pathophysiology of cerebrovascular diseases. In this study, we aimed to investigate the impacts of ischemia and reperfusion (IR) injury on the cerebral microvascular function of rats with high-fat diet-induced MetS.ResultsWe examined Wistar rats fed a high-fat diet (HFD) or normal diet (CTL) for 20 weeks underwent 30 min of bilateral carotid artery occlusion followed by 1 h of reperfusion (IR) or sham surgery. Microvascular blood flow was evaluated on the parietal cortex surface through a cranial window by laser speckle contrast imaging, functional capillary density, endothelial function and endothelial–leukocyte interactions by intravital videomicroscopy. Lipid peroxidation was assessed by TBARs analysis, the expression of oxidative enzymes and inflammatory markers in the brain tissue was analyzed by real-time PCR. The cerebral IR in MetS animals induced a functional capillary rarefaction (HFD IR 117 ± 17 vs. CTL IR 224 ± 35 capillary/mm2; p < 0.05), blunted the endothelial response to acetylcholine (HFD IR −16.93% vs. CTL IR 16.19% from baseline inner diameter p < 0.05) and increased the endothelial–leukocyte interactions in the venules in the brain. The impact of ischemia on the cerebral microvascular blood flow was worsened in MetS animals, with a marked reduction of cerebral blood flow, exposing brain tissue to a higher state of hypoxia.ConclusionsOur results demonstrate that during ischemia and reperfusion, animals with MetS are more susceptible to alterations in the cerebral microcirculation involving endothelial dysfunction and oxidative stress events.
Highlights
Metabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia
Hemodynamic and metabolic effects of high‐fat diet‐induced metabolic syndrome in rats Table 1 summarizes the characteristics of the rats in the CTL or high-fat diet (HFD) groups without the ischemia and reperfusion (IR) procedure
Effects of ischemia and reperfusion on cerebral microvascular blood flow The laser speckle contrast imaging revealed that the basal values of microvascular brain blood flow were significantly reduced in the HFD group (183 ± 21 arbitrary perfusion units (APU), p < 0.05) when compared to CTL group (227 ± 20 APU)
Summary
Metabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia. Cerebrovascular diseases are characterized by brain dysfunction caused by abnormalities of the cerebral circulation, mainly alterations of the cerebral blood supply, including ischemic and hemorrhagic stroke [1] Various conditions, such as aging, hypertension, hypercholesterolemia, diabetes, obesity and atherosclerosis are known to enhance cerebrovascular risk, promote cerebral In this context, the ischemia–reperfusion (IR) injury plays an important role in stroke pathophysiology. Obadia et al BMC Neurosci (2017) 18:67 are, at least in part, due to increased oxidative stress, neuro-inflammation, and impaired vascular reactivity with a progressive decline in microvascular density [5, 6] These pathological adaptations damage cerebral vascular auto-regulation and blood flow reserve, leading to cognitive impairment and dementia [7, 8]
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