2007 Fiscal Year Final Research Report Summary
The effect of intrauterine inflammation on fetal cerebral hemodynamics and white matter injury in the chronically instrumented fetal sheep
| Project/Area Number |
18591213
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
MATSUDA Tadashi Tohoku University, Tohoku University Hospital, Associate Professor (50361100)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Tatsuya Tohoku University Hospital, 病院, Associate Professor (70400380)
HANITA Takushi Tohoku University Hospital, 病院, Senior Residents (30400360)
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| Project Period (FY) |
2006 – 2007
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| Keywords | intrauterine inflammation / cerebral blood flow / brain sparing effect / cerebral ischemia / cerebral white matter damage / periventricular leukomalacia / fetus / sheep |
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| Research Abstract |
We developed an animal model of fetal cerebral white matter injury (WMl) associated with inflammation in stem to clarify the pathogenesis of and preventive measures against it using chronically instrumented fetal sheep; intrauterine inflammation, induced by the infusion with intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin, led fetal hypoxia and then resulted in a compensatory increase of fetal cerebral blood flow, i. e., brain span effect (BSE). Subsequently, at 24 hours after the endotoxin infusion, anemic hypoxia as a hemodynamic insult induced sudden cessation of BSE and resulted in focal WMI. In the current experiment using this model, fetal sheep were divided into 4 groups. In an oxygen supplement group (n=3), the hemodynamic insult was performed after the BSE bad been already cancelled by maternal oxygen supplement. In an anti-inflammation group (n=2), fetuses were administered dexamethasone simultaneously with the BSE induction before the hemodynamic insult. In a pan-inflammation group (n=2), anemic hypoxia was done again after the initial anemic insult induced the BSE without the inflammatory preparation. Neither inflammatory nor hypoxic insult was done in a control group (n 3). Consequently, periventricular focal and/or subcortical multi-focal WMI was found in 2 of the 3 fetuses in the oxygen supplement group, 1 of the 2 in the anti-inflammation group and 2 of the 2 in the non-inflammation group but none in the control group. Based on these results, it was considered that (1) sudden cessation of BSE, even if induced by inflammation, or hypoxia, might be essential in the genesis of fetal cerebral WMI and (2) both oxygen supplement and dexamethasone might be unable to prevent the development of the WMI associated with BSE.
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