| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toru Okayama University, Hospital, Department of Anesthesiology, Senior Assistant Professor (40252952)
YAMAAI Yuichiro Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Oral Function and Anatomy, assistant professor (00158057)
MIYAWAKI Takuya Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Disability and Oral Sciences, and Dental Anesthesiology, Professor (00219825)
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| Research Abstract |
In last year, Fe-NTA was injected into peritoneal fluid. In this year, Fe-NTA was administered with intracerebroventricular (icv) injection in order to avoid effects on peripheral tissue. Fe-NTA solusion (Fe 0.1mg/ml, 0.25 μl/hr) was administered continuously into lateral ventricle using osmotic pump and brain infusion kit, and changes of the brains were evaluated. In control, normal saline solution was administered by icy injection in a same manner. After 2 weeks administration, hypothalamus, cerebral cortex, hippocampus, and striatum were dissected, and evaluated in mRNA of hemeoxygenase (HO)-1, IL-6 and superoxidedismutase (SOD) 2 with real-time PCR. Levels of HO-1 and IL-6 mRNA was raised, but SOD 2 mRNA was stable. After 4 weeks administration of Fe-NTA, brain sections were stained in HE, Pearl stain, and TUNEL. In quantitative evaluation, 4-hydroxy-2-nonenal (4-HNE) was measured by dot blot, and mRNAs of HO-1, IL-6, TNFα, SOD 1, SOD 2, SOD 3, Bc12, Bad, and FasL were analyzed by real-time PCR in the hippocampus and hypothalamus. As a result, hippocampus was damaged remarkably and replaced with inflammatory tissue in HE staining. Iron localized between inflammatory tissue and normal tissue. Apoptosis was induced in neuronal cells in same area as iron localization. Significant increases were observed in 4-HNE, HO-1, IL-6, IL-1β, and TNFα mRNA in the hippocampus and hypothalamus. In control, those changes were not observed. Given together, inflammation and oxidative changes were induced by icy injection of Fe-NTA. And since the hippocampus was damaged remarkably, it may be vulnerable to oxidative stress caused by Fe-NTA.
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