1992 Fiscal Year Final Research Report Summary
MRS studies on protective reactions of neonatal cerebral neurons against acidosis
| Project/Area Number |
03670503
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
YOSHIOKA Hiroshi Kyoto Prefectural University of Medicine Department of Pediatrics Assistant Professor, 医学部, 講師 (50128724)
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| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Ko Kyoto Prefectural University of Medicine Department of Pediatrics Assistant Prof, 医学部, 助手 (80228444)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Acidosis / Hypoxia / Neonate / Neuron / Magnetic resonance / Protective reaction |
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| Research Abstract |
1. Cerebral energy metabolism in newborn mice was investigated during and after 8-hour hypoxia produced by exposure to a 5% oxygen, 95% nitrogen mixture by 31P magnetic resonance spectroscopy. PCr/Pi ratio decreased from a control value of 1.55 to 0.56 at the end of hypoxia. The brain intracellular pH (pHi) increased from 7.20 to 7.36 within 1 hour and stayed higher than control throughout the hypoxic period. The control value of mixed arterial and venous blood pH (pHb) was 7.39. pHb decreased immediately after the induction of hypoxia and fell to 7.16 at the end of hypoxia. These results suggest that there may be an unknown protective system in neonatal brain against systemic acidosis.
2. The effects of hypercapnic acidosis on neuronal activity and mitochondrial respiration were studied in the neonatal canin brain with EEG and 31P-MRS. Inspired CO2 levels of 13, 20, and 30% were administered through a ventilator and resulted in 3 levels of hypercapnia where measured PaCO2 values were approximately 70, 100, 140mmHg. pHi was reduced from 7.11 to 6.99, 6.87, and 6.76 in response to the increasing levels of hypercapnia, and free ADP decreased from 21.5 to 18.1, 14.8 and 12.9uM. The cerebral electrical activity was reduced by 20, 30, and 40%. The change in ADP concentration with respect to EEG output was fitted with the Michaelis-Menten relationship for the mitochondrial oxidative phosphorylative enzymes. This study provides evidence that free ADP regulates mitochondrial respiration during hypercapnic acidosis and that acidosis does not inhibit the mitochondrial substrate regulation of respiration.
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[Publications] Iino, S., Yoshioka, H., Osamura, T., Goma, H., Okano, S., Sawata, T., Kusunoki, T.: "Chronic cerebral lesions of mice following neonatal severe hemorrhagic hypoxic-ischemic encephalopathy." Brain Dysfunction. 4. 155-162 (1991)
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[Publications] Yoshioka, H., Papadopoulos, M, D., Younkin, D. P., Chance, B., Mitsufuji, N., Sawada, T.: "Metabolic kinetics" No To Hattatsu (in Japanese). 24. 159-163 (1992)
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[Publications] Yoshioka, Hasewgawa, Matsuo, Y., Hirai, K., Kawase, S., Morioka, H., Sawada, T., Oono, Y., Hirao, K., Oka, K.: "Quantitative measurements of cerebral blood volume in neonates by near-infrared spectroscopy with multi-points method : a preliminary report." Igaku No Ayumi (in Japanese).
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