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Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.

Dziennis S, Yang D, Cheng J, Anderson KA, Alkayed NJ, Hurn PD, Lein PJ - Environ. Health Perspect. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Peri-Operative Medicine, Oregon Health & Science University, Portland, Oregon 97239, 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 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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Related in: MedlinePlus

Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on infarct volume measured after 22 hr of reperfusion following MCAO in female (8–10 weeks of age) and male rats (6–8 weeks of age); see “Materials and Methods” for details. Representative photomicrographs of TTC-stained coronal slices demonstrating infarcts (nonstained region) in the ipsilateral (left) cortex and striatum of females from vehicle control (A) and 0.1-mg/kg/day (B) treatment groups. Infarct size was significantly reduced in the striatum of females (C) and males (D) in the 0.1- and 1.0-mg/kg A1254 groups, respectively. Data are presented as the mean ± SE. n = 7–9 per treatment group.*p < 0.05.
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f3-ehp0116-000474: Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on infarct volume measured after 22 hr of reperfusion following MCAO in female (8–10 weeks of age) and male rats (6–8 weeks of age); see “Materials and Methods” for details. Representative photomicrographs of TTC-stained coronal slices demonstrating infarcts (nonstained region) in the ipsilateral (left) cortex and striatum of females from vehicle control (A) and 0.1-mg/kg/day (B) treatment groups. Infarct size was significantly reduced in the striatum of females (C) and males (D) in the 0.1- and 1.0-mg/kg A1254 groups, respectively. Data are presented as the mean ± SE. n = 7–9 per treatment group.*p < 0.05.

Mentions: To test the hypothesis that developmental PCB exposure influences adult sensitivity to ischemic brain injury, we performed transient MCAO in adult rats exposed throughout gestation and lactation to A1254 in the maternal diet. The survival rate was 100% in all treatment groups. Arterial blood pressure and gases, body temperature, and laser Doppler perfusion values were monitored throughout surgery, MCAO, and early reperfusion. Physiologic values obtained from the midpoint of MCAO were generally comparable between treatment groups (Table 1). While mean arterial blood pressure and blood glucose were significantly decreased in a subset of A1254 dose groups, these lower values were still well within the normal physiologic range for these parameters. However, relative to vehicle controls (Figure 3A), infarct volume was significantly decreased in both females and males exposed developmentally to A1254, although in females this effect was observed only in the lower A1254 dose group (Figure 3B,C) and in males only in the higher A1254 dose group (Figure 3D). Although similar trends were noted in the cortex and total hemisphere, significant treatment-related effects were limited to the striatum.


Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.

Dziennis S, Yang D, Cheng J, Anderson KA, Alkayed NJ, Hurn PD, Lein PJ - Environ. Health Perspect. (2008)

Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on infarct volume measured after 22 hr of reperfusion following MCAO in female (8–10 weeks of age) and male rats (6–8 weeks of age); see “Materials and Methods” for details. Representative photomicrographs of TTC-stained coronal slices demonstrating infarcts (nonstained region) in the ipsilateral (left) cortex and striatum of females from vehicle control (A) and 0.1-mg/kg/day (B) treatment groups. Infarct size was significantly reduced in the striatum of females (C) and males (D) in the 0.1- and 1.0-mg/kg A1254 groups, respectively. Data are presented as the mean ± SE. n = 7–9 per treatment group.*p < 0.05.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2291013&req=5

f3-ehp0116-000474: Effects of A1254 exposure [0 (vehicle), 0.1, or 1 mg/kg] on infarct volume measured after 22 hr of reperfusion following MCAO in female (8–10 weeks of age) and male rats (6–8 weeks of age); see “Materials and Methods” for details. Representative photomicrographs of TTC-stained coronal slices demonstrating infarcts (nonstained region) in the ipsilateral (left) cortex and striatum of females from vehicle control (A) and 0.1-mg/kg/day (B) treatment groups. Infarct size was significantly reduced in the striatum of females (C) and males (D) in the 0.1- and 1.0-mg/kg A1254 groups, respectively. Data are presented as the mean ± SE. n = 7–9 per treatment group.*p < 0.05.
Mentions: To test the hypothesis that developmental PCB exposure influences adult sensitivity to ischemic brain injury, we performed transient MCAO in adult rats exposed throughout gestation and lactation to A1254 in the maternal diet. The survival rate was 100% in all treatment groups. Arterial blood pressure and gases, body temperature, and laser Doppler perfusion values were monitored throughout surgery, MCAO, and early reperfusion. Physiologic values obtained from the midpoint of MCAO were generally comparable between treatment groups (Table 1). While mean arterial blood pressure and blood glucose were significantly decreased in a subset of A1254 dose groups, these lower values were still well within the normal physiologic range for these parameters. However, relative to vehicle controls (Figure 3A), infarct volume was significantly decreased in both females and males exposed developmentally to A1254, although in females this effect was observed only in the lower A1254 dose group (Figure 3B,C) and in males only in the higher A1254 dose group (Figure 3D). Although similar trends were noted in the cortex and total hemisphere, significant treatment-related effects were limited to the striatum.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Peri-Operative Medicine, Oregon Health & Science University, Portland, Oregon 97239, 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 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.

Show MeSH
Related in: MedlinePlus