2003 Fiscal Year Final Research Report Summary
Investigation of neuroprotctive effect of glial cell line-derived neurotrophic factor in neonatal central and peripheral nervous system
| Project/Area Number |
14370535
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | (Miyazaki Medical College) University of Miyazaki |
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Principal Investigator |
IKENOUE Tsuyomu Miyazaki Medical College, University of Miyazaki, Dept. OB & GYN, Professor, 医学部, 教授 (60232211)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Tomoaki Miyazaki Medical College, University of Miyazaki, Perinatal Center, Assistant Professor, 医学部, 講師 (80202894)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Glial cell line-derived neurotrophic factor / Neonate / Fetus / Hypoxia-icchemia / Free radical / Edaravone / Erb's palsy / Slowly progressive brain damage |
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| Research Abstract |
(A)We examined the effect of Glial cell line-derived neurotrophic factor (GDNF), newly discovered neuroprotective neurotrophin in neonatal rat model.
1)We have shown that the infarction is reduced by direct injection of GDNF immediately after the hypoxic-ischemic insult. For the purpose of clinical application, we developed a delivery system, which enabled the constant supply of GDNF to the brain. Encapsulated GDNF-secreting cells, which was produced with bioengineering technique, was implanted 48hrs prior to hypoxic-ischemic insult. The GDNF capsule significantly reduced the infarction volume in the brain of neonatal hypoxic-ischemic encephalopathy rat model.
2)Local administration of GDNF in a neonatal preganglionic Erb's palsy model resulted in significant improvement in deficits on the basis of behavioral and histological evaluations.
(B)A newly developed free radical scavenger, edaravone, which is commonly used as the first choice of drug for adult cerebral ischemia, was examined for
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the ability of neuroprotection in neonatal rat model of hypoxic-ischemic encephalopathy.
1)The optimal duration of edaravone administration at the dosage of 9mg/kg was evaluated in terms of histological and behavioral improvement. Acute (2 and 5 days) edaravone therapy has greater effect on neonatal hypoxic-ischemic brain damage than that of chronic (10 days) therapy.
2)Edaravone significantly decreased the production of reactive oxygen radicals in the neonatal examined with microdialysis method during hypoxic-ischemic stress.
3)In the neonatal hypoxic-ischemic encephalopathy model, edaravone-treated rat group showed the ability to reduce nitroxide radical even in the contralateral hemisphere at the age of 6 wk.
(C)Long-term follow up study of an unilateral hypoxic-ischemic encephalopathy rat model revealed compensative hypertrophy of the contralateral brain hemisphere which was observed within 5 wks after the insult. The volume of the both hemispheres were gradually decreased subsequently. We named this phenomenon as "slowly progressive brain damage". Less
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