Hyperlipidemia disrupts cerebrovascular reflexes and worsens ischemic perfusion defect
Hyperlipidemia disrupts cerebrovascular reflexes and worsens ischemic perfusion defect
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DOI：
10.1038/jcbfm.2013.38
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发表时间：
2013-06-01
影响因子：
6.3
通讯作者：
Huang, Paul L.
中科院分区：
文献类型：
--
作者：
Ayata, Cenk;Shin, Hwa Kyoung;Huang, Paul L.
高血压是冠状动脉和颈动脉粥样硬化和中风的一个非常普遍的危险因素。然而，即使没有明显的动脉粥样硬化，高脂血症也会破坏内皮和平滑肌功能。我们研究了高脂血症对静息脑灌注、基本脑血管反射和高脂血症载脂蛋白E基因敲除小鼠急性局灶性缺血期间血流限制性动脉粥样硬化狭窄发展之前的动态灌注缺损的影响。尽管血压升高，绝对静息脑血流量减少了20%，载脂蛋白E基因敲除与野生型相比，当测量[C-14]-碘苯丙胺技术。非侵入性，高时空分辨率激光散斑流成像显示，载脂蛋白E基因敲除小鼠（60与40毫米汞柱）的自我调节下限升高，皮质充血反应高碳酸血症和功能激活分别减弱了30%和64%。与野生型相比，载脂蛋白E基因敲除的大脑中动脉远端闭塞导致显著更大的灌注缺损和梗死体积。脑血管功能障碍与高脂饮食的持续时间有直接关系。这些数据表明，高脂血症破坏脑血流调节，减少侧支循环灌注在急性中风的血液动力学显着动脉粥样硬化的情况下。
Hyperlipidemia is a highly prevalent risk factor for coronary and cervical atherosclerosis and stroke. However, even in the absence of overt atherosclerosis, hyperlipidemia disrupts endothelial and smooth muscle function. We investigated the impact of hyperlipidemia on resting-brain perfusion, fundamental cerebrovascular reflexes, and dynamic perfusion defect during acute focal ischemia in hyperlipidemic apolipoprotein E knockout mice before the development of flow-limiting atherosclerotic stenoses. Despite elevated blood pressures, absolute resting cerebral blood flow was reduced by 20% in apolipoprotein E knockout compared with wild type when measured by [C-14]-iodoamphetamine technique. Noninvasive, high spatiotemporal resolution laser speckle flow imaging revealed that the lower autoregulatory limit was elevated in apolipoprotein E knockout mice (60 vs. 40 mm Hg), and cortical hyperemic responses to hypercapnia and functional activation were attenuated by 30% and 64%, respectively. Distal middle cerebral artery occlusion caused significantly larger perfusion defects and infarct volumes in apolipoprotein E knockout compared with wild type. Cerebrovascular dysfunction showed a direct relationship to the duration of high-fat diet. These data suggest that hyperlipidemia disrupts cerebral blood flow regulation and diminishes collateral perfusion in acute stroke in the absence of hemodynamically significant atherosclerosis.