2006 Fiscal Year Final Research Report Summary
Investigation of cerebral paralysis and its development of new drugs in neonatal hypoxic-ischemia-induced slowly progressive brain damage
| Project/Area Number |
17590479
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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 |
Applied pharmacology
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| Research Institution | Fukuoka University |
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Principal Investigator |
MISHIMA Kenichi Fukuoka University, Pharmaceutical Science, Assistant Professor, 薬学部, 助手 (00320309)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Michihiro Fukuoka University, Pharmaceutical Science, Professor, 薬学部, 教授 (10091331)
IWASAKI Katsunori Fukuoka University, Pharmaceutical Science, Professor, 薬学部, 教授 (10183196)
IKEDA Tomoaki National Cardiovascular Center, Perinatology, Director, 周産期科, 部長 (80202894)
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| Project Period (FY) |
2005 – 2006
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| Keywords | neonate / astrocyte / hypoxia-ischemia / corticosterone / learning and memory |
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| Research Abstract |
The present study was designed to determine potential associations between the brain damage induced by hypoxic-ischemic (HI) insult and spatial learning impairment in 8-arm radial maze task. The brain damage was progressed from 2 weeks of recovery and up to 17 weeks of recovery. The magnetic resonance imaging (MRI) changes were similar with the histological changes, and the brain damages were exacerbated in contralateral hemisphere after 57 weeks of recovery following the HI. The spatial learning impairments of 8-arm radial maze starting at 16 weeks of recovery were more severe than those at 7 weeks of recovery, indicating that the spatial learning impairments were progressive and depended on the degree of brain damage. Therefore we called this phenomenon, slowly progressive brain damage (SPBD, Nuerosci Lett, 376,194-199,2005). We examined this mechanism of the SPBD.
1) The time course of astrocyte in thalamus and hypothalamus The GFAP-positive cell progressively increased in the thalamus from 2 weeks and in the hypothalamus from 9 weeks after the HI. The S-100 protein-positive cells were observed in both thalamus and hypothalamus 17 weeks after the HI.
2) The time course of glutamate, NOx and corticosterone in the CSF The glutamate decreased from 2 weeks to 17 weeks after the HI, and the NOx increased from 9 weeks after the HI. The corticosterone tended to decrease in the female rats.
3) Effect of the CSF at 17 weeks after the HI on the CRT task in intact rats.
The CSF was corrected at 17 weeks after the HI and was injected i.c.v. in intact rats. The CSF (20-40 uL) did not affect the CRT task.
These results suggest that the SPBD was related to the activating of astrocyte in the hypothalamus, a decrease in the glutamate and an increase in the NOx.
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Research Products
(11 results)
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[Journal Article] High-cholesterol feeding aggravates cerebral infarction via decreasing the CB(1) receptor.2007
Author(s)
Hayakawa K, Mishima K, Nozako M, Hazekawa M, Aoyama Y, Ogata A, Harada K, Fujioka M, Abe K, Egashira N, Iwasaki K, Fujiwara M
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Journal Title
Neurosci Lett. 414
Pages: 183-187
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Delta(9)-tetrahydrocannabinol (Delta(9)-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.2007
Author(s)
Hayakawa K, Mishima K, Nozako M, Hazekawa M, Ogata A, Fujioka M, Harada K, Mishima S, Orito K, Egashira N, Iwasaki K, Fujiwara M
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Journal Title
Life Sci. 80
Pages: 1466-1471
Description
「研究成果報告書概要(和文)」より
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[Journal Article] High-cholesterol feeding aggravates cerebral infarction via decreasing the CB(1) receptor.2007
Author(s)
Hayakawa K, Mishima K, Nozako M, Hazekawa M, Aoyama Y, Ogata A, Harada K, Fujioka M, Abe K, Egashira N, Iwasaki K, Fujiwara M.
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Journal Title
Neurosci Lett. 414
Pages: 183-187
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Delta(9)-tetrahydrocannabinol (Delta(9)-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.2007
Author(s)
Hayakawa K, Mishima K, Nozako M, Hazekawa M, Ogata A, Fujioka M, Harada K, Mishima S, Orito K, Egashira N, Iwasaki K, Fujiwara M.
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Journal Title
Life Sci. 80
Pages: 1466-1471
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats.2005
Author(s)
Katsuragi S, Ikeda T, Date I, Shingo T, Yasuhara T, Mishima K, Aoo N, Harada K, Egashira N, Iwasaki K, Fujiwara M, Ikenoue T
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Journal Title
Am J Obstet Gyneco 192
Pages: 1028-1037
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Short-Term Administration of a New Free Radical Scavenger, Edaravone, Is More Effective Than its Long-Term Administration for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy.2005
Author(s)
Noor JI, Ikeda T, Mishima K, Aoo N, Ohta S, Egashira N, Iwasaki K, Fujiwara M, Ikenoue T
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Journal Title
Stroke 36
Pages: 2468-2474
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Short-Term Administration of a New Free Radical Scavenger, Edaravone, Is More Effective Than its Long-Term Administration for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy.2005
Author(s)
Noor JI, Ikeda T, Mishima K, Aoo N, Ohta S, Egashira N, Iwasaki K, Fujiwara M, Ikenoue T.
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Journal Title
Stroke 36
Pages: 2468-2474
Description
「研究成果報告書概要(欧文)」より
