2001 Fiscal Year Final Research Report Summary
Investigation of therapy for neonatal hypoxic-ischemic brain damage
| Project/Area Number |
12470345
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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 | 宮崎医科大学 |
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Principal Investigator |
IKENOUE Tsuyomu Miyazaki Medical College, Dept. OB & GYN, Professor, 医学部, 教授 (60232211)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Tomoaki Miyazaki Medical College, Perinatal Center, Assistant Professor, 医学部, 講師 (80202894)
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| Project Period (FY) |
2000 – 2001
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| Keywords | hypoxic-ischemic brain damage / glial cell line-derived neurotrophic facto / rat / neonate / glucocorticoid / brachial plexus injury / cerebrospinal fluid |
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| Research Abstract |
Glial cell line-derived neurotrophic factor (GDNF) was discovered as a potent neurotrophic factor to the dopaminergic neurons in the midbrain at 1993. The subsequent studies revealed its trophic effect on the motor neuron and beneficial effect on brain edema. We have investigated the involvement of GDNF in neonatal hypoxic-ischemic brain damage as follows.
(1) Intraparenchymal administration of 2μg and 4μg of GDNF provided remarkable protection against ischemia/hypoxia-induced brain damage in 7-day-old rats in a dose-dependent manner.
(2) Expression of GDNF in developing rat brain form post natal day (PND) 1 to 14 and on PND 21 was examined immunocytochemically. The results revealed the characteristic developmental shifts in GDNF expression in neuronal and non-neuronal cells, which indicated that GDNF may be of critical importance at different stages of brain growth and differentiation. ELISA of the cerebrospinal fluid (CSF) revealed a rapid rise in GDNF levels from PND 1 to peak levels at PND 7-9, and thereafter, the levels gradually decreased.
(3) In hypoxic-ischemic brain damage model of 7-day-old rat, brain GDNF levels took two peak, 3 and 48 hours after the insult. Immunocytochemical study showed that the former peak was represented by GDNF production in neurons and the latter peak was corresponded by that in migrating astrocytes.
(4) Administration of dexamethasone (0.5 mg/kg) for 3 days beginning from PND 1 significantly increased GDNF levels in the CSF at PND 3-5. However, GDNF levels in the CSF in the group which receive dexamethasone in the early life were lower than that in the control group at PND 10.
(5) We established the neonatal rat model mimicking upper brachial plexus palsy in newborn, in which the behavioral and histological changes could be evaluated. Topical application of gelform soaked with 4μg of GDNF dramatically improved the behavioral and histological impairment.
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