Docosahexaenoic acid improves behavior and attenuates blood-brain barrier injury induced by focal cerebral ischemia in rats.
Docosahexaenoic acid improves behavior and attenuates blood-brain barrier injury induced by focal cerebral ischemia in rats.
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Docosahexaenoic酸改善了行为，并减轻大鼠局灶性脑缺血引起的血脑屏障损伤。
DOI：
10.1186/s13231-014-0012-0
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Belayev L
中科院分区：
文献类型：
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作者：
Hong SH;Khoutorova L;Bazan NG;Belayev L
缺血性脑损伤破坏血脑屏障（BBB），然后引发一系列事件，导致水肿形成，继发性脑损伤和不良的神经功能结局。最近，我们发现二十二碳六烯酸（DHA）可以改善实验性中风后的功能和组织学结局。然而，DHA对脑缺血再灌注损伤后血脑屏障功能障碍的影响知之甚少。本研究旨在确定DHA是否对大鼠局灶性脑缺血后BBB破坏具有保护作用。生理控制的SD大鼠接受大脑中动脉阻塞（MCAo）2 h。在MCAo发作后3 h静脉内给予DHA（5 mg/kg）或溶媒（生理盐水）。在MCAo后6 h、24 h或72 h在8个脑区进行伊文思蓝染料（EB）的荧光定量。在中风后第3天评估异硫氰酸异黄绿素（FITC）-葡聚糖渗漏和组织病理学。生理变量稳定，组间无显著差异。DHA在24 h、48 h和72 h改善了神经功能缺损，并在6 h（30%）、24 h（48%）和72 h（38%）减少了缺血半球的EB外渗。此外，在皮质和整个半球中，DHA也减少了EB外渗。与生理盐水组相比，DHA治疗第3天的FITC-葡聚糖渗漏减少了68%。在中风后第3天，与溶剂处理的大鼠相比，DHA处理减少了皮质（50%）和总梗死体积（38%）。DHA治疗减少BBB损伤，伴随着行为恢复的加速和梗死体积的减小。这是合理的建议，DHA有可能治疗局灶性缺血性中风的临床设置。
Ischemic brain injury disrupts the blood–brain barrier (BBB) and then triggers a cascade of events, leading to edema formation, secondary brain injury and poor neurological outcomes. Recently, we have shown that docosahexaenoic acid (DHA) improves functional and histological outcomes following experimental stroke. However, little is known about the effect of DHA on BBB dysfunction after cerebral ischemia-reperfusion injury. The present study was designed to determine whether DHA protects against BBB disruption after focal cerebral ischemia in rats. Physiologically-controlled SD rats received 2 h middle cerebral artery occlusion (MCAo). DHA (5 mg/kg) or vehicle (saline) was administered I.V. at 3 h after onset of MCAo. Fluorometric quantitation of Evans Blue dye (EB) was performed in eight brain regions at 6 h, 24 h or 72 h after MCAo. Fluorescein isothiocynate (FITC) - dextran leakage and histopathology was evaluated on day 3 after stroke. Physiological variables were stable and showed no significant differences between groups. DHA improved neurological deficits at 24 h, 48 h and 72 h and decreased EB extravasation in the ischemic hemisphere at 6 h (by 30%), 24 h (by 48%) and 72 h (by 38%). In addition, EB extravasation was decreased by DHA in the cortex and total hemisphere as well. FITC-dextran leakage was reduced by DHA treatment on day 3 by 68% compared to the saline group. DHA treatment attenuated cortical (by 50%) and total infarct volume (by 38%) compared to vehicle-treated rats on day 3 after stroke. DHA therapy diminishes BBB damage accompanied with the acceleration of behavioral recovery and attenuation of the infarct volume. It is reasonable to propose that DHA has the potential for treating focal ischemic stroke in the clinical setting.