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Suzan Dziennis,^1* Dongren Yang,^2* Jian Cheng,¹ Kim A. Anderson,³ Nabil J. Alkayed,¹ Patricia D. Hurn,¹ and Pamela J. Lein²

¹Department of Anesthesiology and Peri-Operative Medicine, and ²Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USA; ³Environmental & Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA

Abstract
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 polychlorinated 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.

Key words: Aroclor 1254, cerebral ischemia, developmental origins of adult disease, polychlorinated biphenyls, stroke. Environ Health Perspect 116:474–480 (2008) . doi:10.1289/ehp.10828 available via http://dx.doi.org/ [Online 14 January 2008]

Address correspondence to P.J. Lein, 3181 SW Sam Jackson Park Rd., CROET/L606, Oregon Health & Science University, Portland, OR 97239 USA. Telephone: (503) 494-9279. Fax: (503) 494-3849. E-mail: leinp@ohsu.edu

*These authors contributed equally to this work.

This research was supported by grants from the National Institutes of Health (ES010338 and NS046649 to P.J.L. ; NS49210 to P.D.H. and N.J.A. ; NS33668 to P.D.H. ; NS44313 to N.J.A. ; and F32 Ruth L. Kirschstein NRSA to S.D.) .

The authors declare they have no competing financial interests.

Received 30 August 2007 ; accepted 14 January 2008.