Effect of resolvin D1 on focal cerebral ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the effect of resolvin D1 on focal cerebral ischemia-reperfusion (I/R) injury in rats. Methods One hundred and twenty adult male Sprague-Dawley rats, aged 7 weeks, weighing 260-280 g, were randomly divided into 5 groups (n=24 each) using a random number table: sham operation group (group S) , group I/R, low-dose resolvin D1 group (group LRD) , medium-dose resolvin D1 group (group MRD) , and high-dose resolvin D1 group (group HRD) . Focal cerebral I/R was induced by right middle cerebral artery occlusion using a nylon thread inserted into internal carotid artery and advanced cranially until resistance was met.The occlusion was maintained for 2 h followed by 24 h reperfusion.In LRD, MRD and HRD groups, 0.03, 0.10, 0.30 nmol resolvin D1 5 μl was injected into the lateral cerebral ventricle at the beginning of reperfusion, respectively.Neurological deficits were evaluated at 24 h of reperfusion and scored.The rats were then sacrificed, and their brains were removed for determination of infarct volume (by TTC staining) , cerebral water content, Evans blue content and expression of matrix metalloproteinase-9 (MMP-9) in the ischemic cortex. Results Compared with group S, the neurological deficit scores, cerebral infarct volume, and cerebral water and Evans blue content were significantly increased, and the expression of MMP-9 was up-regulated in the other 4 groups.Compared with group I/R, the neurological deficit scores, cerebral infarct volume, and cerebral water and Evans blue content were significantly decreased, and the expression of MMP-9 was down-regulated in group MRD and group HRD, and no significant change was found in the parameters mentioned above in group LRD. Conclusion Resolvin D1 can attenuate focal cerebral I/R injury in rats, and down-regulation of MMP-9 expression and decrease in permeability of blood-brain barrier may be involved in the mechanism. Key words: Docosahexaenoic acids; Reperfusion injury; Cerebral