Abstract
ObjectiveTo investigate whether irisin could protect against blood–brain barrier (BBB) dysfunction following focal cerebral ischemia/reperfusion in rats.Methods and MaterialsSeventy‐two adult male Sprague Dawley rats weighing 280–320 g were randomly divided into three groups: sham operation group (S), focal cerebral ischemia/reperfusion group (FC), and irisin group (IR). Focal cerebral ischemia was induced by improved thread occlusion of right middle cerebral artery (MCAO) for 2 hr followed by reperfusion for 24 hr in rats. After 24 hr of reperfusion, the neurological evaluation was performed by the method of Longa's score. The histopathological changes were observed by HE staining. The brain water content was determined by detecting the wet weight and dry weight. The BBB permeability was assessed by fluorescence spectrophotometer and fluorescence microscopy for Evans blue (EB) extravasation. The activity and expression of matrix metalloproteinase‐9 (MMP‐9) in different groups were detected by immunohistochemical staining, Western blot, and gel gelatin zymography.ResultsAfter MCAO, the neurological deficit scores, the infarct volume, the brain water content, and the EB content were higher in the FC group than those in the S group (p < .05). While after irisin treatment, these indicators mentioned above were lower than those in the IR group (p < .05). Moreover, the protein expression of MMP‐9 in the cortex increased significantly after MCAO, while irisin treatment could decrease the protein expression of MMP‐9 in the cortex (p < .05).ConclusionOur data suggest that irisin can attenuate brain damage both morphologically and functionally and protect BBB from disruption after focal cerebral ischemia/reperfusion, which is highly associated with the inhibition of the expression and activity of MMP‐9 in the brain tissue.
Highlights
Acute ischemic stroke (AIS) is one of the main reasons for morbid‐ ity and death worldwide, especially during perioperative period, and the incidence of AIS is generally 0.08%–0.4% in surgeries and anesthesia (Froehler et al, 2017; Wu, Guo, Jin, & Ke, 2018; Wu, Tang, Tai, & Yao, 2018)
Rats were randomly divided into three groups: (a) sham operation group (S), a healthy control group that subjected to sham operation; (b) focal cerebral ischemia/reperfusion group (FC), a FC group that underwent the occlusion of right middle cerebral artery (MCAO) for 2 hr followed by reperfusion for 24 hr; and (c) irisin group (IR), an IR group that underwent middle cerebral artery occlusion (MCAO) injury at 30 min after pretreatment with 10 μg/kg irisin intravenously
At 24 hr after reperfusion, our zymography analysis revealed that the expression of activated matrix metalloproteinase‐9 (MMP‐9) increased in the FC group and IR group, while the treatment of irisin significantly lightened the intensity of the Matrix metalloproteinases (MMPs)‐9 band
Summary
Acute ischemic stroke (AIS) is one of the main reasons for morbid‐ ity and death worldwide, especially during perioperative period, and the incidence of AIS is generally 0.08%–0.4% in surgeries and anesthesia (Froehler et al, 2017; Wu, Guo, Jin, & Ke, 2018; Wu, Tang, Tai, & Yao, 2018). This leads to deterioration of the disease and greatly influ‐ ences clinical prognosis (Gardner & Ghorpade, 2003; Kamada et al, 2007; Strbian et al, 2008). Stroke patients with lower irisin concentration level in their serum had poor prognosis and cognitive function recovery (Wu, Guo, et al, 2018; Wu, Tang, et al, 2018) In this perspective, it is reasonable for us to speculate that treatment of irisin can exert certain impact upon the occurrence and development of cardiovascular and cere‐ brovascular diseases. Based on the previous studies, this study is intended to explore the effects of irisin treatment on BBB permeability after focal ce‐ rebral ischemia/reperfusion in rats, and to explore its possible mechanism
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