Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.
Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.
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DOI：
10.1289/ehp.10828
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发表时间：
2008-04
影响因子：
10.4
通讯作者：
Lein PJ
中科院分区：
文献类型：
--
作者：
Dziennis S;Yang D;Cheng J;Anderson KA;Alkayed NJ;Hurn PD;Lein PJ
“成人疾病的发育起源”假说最初是从将低出生体重与包括中风在内的心血管疾病联系起来的证据中得出的。随后，它已扩大到包括发育暴露于环境污染物作为成人发病的风险因素。我们在这项研究中的目标是测试的假设，发育暴露于多氯联苯（PCBs）改变中风的结果在成年人。在整个妊娠期和哺乳期，我们在母体饮食中以0.1或1 mg/kg/天的剂量将大鼠暴露于PCB混合物Aroclor 1254（A1254）。在6-8周龄时通过大脑中动脉闭塞诱导局灶性脑缺血，并在再灌注22小时时测量大脑皮质和纹状体中的梗死面积。多氯联苯同系物定量在脑组织中的气相色谱与微电子捕获检测，皮质和纹状体Bcl 2和Cyp 2C 11的表达进行了定量逆转录-聚合酶链反应。在0.1和1 mg/kg/天剂量下，A1254的发育暴露分别显著降低了雌性和雄性的纹状体梗死。在接触1毫克/千克/天（而非0.1毫克/千克/天）A1254的成年雌性和雄性动物的大脑中，检测到的主要是邻位取代的多氯联苯同系物高于背景水平。发育A1254暴露对Bcl 2和Cyp 2C 11表达的影响与对梗死体积的影响无关。我们的数据提供了原则的证据，即发育暴露于环境污染物影响成人大脑缺血性损伤的反应，因此代表了中风易感性的潜在重要决定因素。
The “developmental origins of adult disease” hypothesis was originally derived from evidence linking low birth weight to cardiovascular diseases including stroke. Subsequently, it has been expanded to include developmental exposures to environmental contaminants as risk factors for adult onset disease. Our goal in this study was to test the hypothesis that developmental exposure to poly-chlorinated biphenyls (PCBs) alters stroke outcome in adults. We exposed rats to the PCB mixture Aroclor 1254 (A1254) at 0.1 or 1 mg/kg/day in the maternal diet throughout gestation and lactation. Focal cerebral ischemia was induced at 6–8 weeks of age via middle cerebral artery occlusion, and infarct size was measured in the cerebral cortex and striatum at 22 hr of reperfusion. PCB congeners were quantified in brain tissue by gas chromatography with microelectron capture detection, and cortical and striatal expression of Bcl2 and Cyp2C11 were quantified by quantitative reverse transcriptase-polymerase chain reaction. Developmental exposure to A1254 significantly decreased striatal infarct in females and males at 0.1 and 1 mg/kg/day, respectively. Predominantly ortho-substituted PCB congeners were detected above background levels in brains of adult females and males exposed to A1254 at 1 but not 0.1 mg/kg/day. Effects of developmental A1254 exposure on Bcl2 and Cyp2C11 expression did not correlate with effects on infarct volume. Our data provide proof of principle that developmental exposures to environmental contaminants influence the response of the adult brain to ischemic injury and thus represent potentially important determinants of stroke susceptibility.
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影响因子：
11.4
作者：
Decastro, BR;Korrick, SA;Soto, AM
通讯作者：
Soto, AM
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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