Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.
- Author(s): Dziennis, Suzan
- Yang, Dongren
- Cheng, Jian
- Anderson, Kim A
- Alkayed, Nabil J
- Hurn, Patricia D
- Lein, Pamela J
- et al.
Published Web Locationhttps://doi.org/10.1289/ehp.10828
BACKGROUND: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. OBJECTIVE:Our goal in this study was to test the hypothesis that developmental exposure to poly-chlorinated biphenyls (PCBs) alters stroke outcome in adults. METHODS: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. RESULTS: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. CONCLUSION: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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