Lin Y, Xu M, Wan J, Wen S, Sun J, Zhao H, Lou M
Department of Neurology, The Second Affiliated Hospital, Zhejiang University, School of Medicine, #88 Jiefang Road, Hangzhou, China.
Department of Radiology, The Second Affiliated Hospital, Zhejiang University, School of Medicine, #88 Jiefang Road, Hangzhou, China.
Neuroscience. 2015 Aug 20;301:471-9. doi: 10.1016/j.neuroscience.2015.06.024. Epub 2015 Jun 20.
Hemorrhagic transformation (HT) is a feared complication of cerebral ischemic infarction, especially following the use of thrombolytic therapy. In this study, we examined whether docosahexaenoic acid (DHA; 22:6n-3), an omega-3 essential fatty acid family member, can protect the brain from injury and whether DHA can decrease the risk of HT enhanced by hyperglycemia after focal ischemic injury. Male Sprague-Dawley rats were injected with 50% dextrose (6ml/kg intraperitoneally) to induce hyperglycemia 10min before 1.5h of filament middle cerebral artery occlusion (MCAO) was performed. Treatment with DHA (10mg/kg) 5min before reperfusion reduced HT and further improved the 7-day neurological outcome. It also reduced infarct volume, which is consistent with the restricted DWI and T2WI hyperintensive area. Reduced Evans Blue extravasation and increased expression of collagen IV indicated the improved integrity of the blood-brain barrier (BBB) in DHA-treated rats. Moreover, DHA reduced the expression of the intercellular adhesion molecule-1 (ICAM-1) in the ischemic injured brain. Therefore, we conclude that DHA attenuated hyperglycemia-enhanced HT and improved neurological function by preserving the integrity of BBB and reducing inflammation.
出血性转化（HT）是脑缺血性梗死令人担忧的并发症，尤其是在使用溶栓治疗后。在本研究中，我们研究了ω-3必需脂肪酸家族成员二十二碳六烯酸（DHA；22:6n-3）是否能保护大脑免受损伤，以及DHA是否能降低局灶性缺血损伤后高血糖增强的HT风险。在进行1.5小时线栓法大脑中动脉闭塞（MCAO）前10分钟，给雄性Sprague-Dawley大鼠腹腔注射50%葡萄糖（6ml/kg）以诱导高血糖。再灌注前5分钟用DHA（10mg/kg）治疗可减少HT，并进一步改善7天的神经功能结局。它还减少了梗死体积，这与弥散加权成像（DWI）受限和T2加权成像（T2WI）高信号区域一致。伊文思蓝外渗减少和IV型胶原表达增加表明DHA治疗的大鼠血脑屏障（BBB）完整性得到改善。此外，DHA降低了缺血损伤脑中细胞间黏附分子-1（ICAM-1）的表达。因此，我们得出结论，DHA通过维持BBB的完整性和减轻炎症，减轻了高血糖增强的HT并改善了神经功能。
