2002 Fiscal Year Final Research Report Summary
Protective mechanism of fetal brain against hypoxia: in vivo optical recordings
| Project/Area Number |
13671138
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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 | Yamaguchi University |
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Principal Investigator |
SAKATA Yoshiyuki Yamaguchi Univ. Sch. Med. Assistant Professor, 医学部, 講師 (10034927)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Yoshiyuki Yamaguchi Univ. Sch. Med. Assistant, 医学部, 助手 (20325210)
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| Project Period (FY) |
2001 – 2002
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| Keywords | hypoxia / fetal brain / glutamate receptor / non-NMDA / NMDA / Ca^<2+> / optical imaging / in vivo |
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| Research Abstract |
It is known that fetal brain is strong against hypoxia. During delivery, intermittent severe hypoxia on fetus lasts for a long time. However, Almost fetus was born without the brain damage. Therefore, it is thought the fetal brain may have protective mechanism against hypoxia. We studied the protective mechanism by forcusing on glutaminergic synaptic transmission, using the optic imaging system. The termed pregnant rat (Sprague Dawly rat, 3 months old) was anesthetized with uretane (1.2-1.4 g/kg, i. P.). The fetus which was connected with dam by umbilical cord, was fixed on a stereotaxic instrument. The uterus was exposed by caesarean section and partially cut to exposure of the fetus. For electrical stimulation of the fetal superior colliculus (SC), a bipolar electrode (stainless steel wire) was inserted into the rostral part of the SC. Focal stimulation of the SC was made by a single pulse or train pulse (10 pulses) at currents of 1-3 mA. Fluorescent Ca2+ sensitive dye (Fura-2/AM ) w
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as loaded into the SC regions for 90 min. The fractional changes in fluorescence of Ca2+ sensitive dye were recorded by an optical imaging system (ARGUS/HiSCA). The fetus with the dam was set under the microscope. The acute hypoxia was performed with occluding the umbilical cord by a fine clip.
1) [Ca2+]I in SC was increased during with the occlusion of the umbilical cord and recovered gradually after the release of the umbilical cord occlusion. The increased [Ca2+]I was attenuated by NMDA receptor antagonist (AP-5) after pretreatment with non-NMDA receptor antagonist (CNQX ).
2) [Ca2+]I in the SC regions was steeply increased by the focal SC stimulation of the train pulses (the early response). Increasing the stimulus current from 1 to 3 mA produced greater increases in [Ca2+]i. The train pulse stimulation induced a prolonged response (>10 sec) (the late response). The early response was antagonized with CNQX and AP-5. The late response was antagonized by AP-5.
3) At 3hrs after the occlusion of umbilical cord, the early response was induced with the focal SC stimulation, but the late response was markedly reduced. The early response was antagonized by CNQX but not almost by AP-5.
These results suggest that the Ca2+influx following focal SC stimulation and hypoxia in fetal rats is mediated by glutaminergic synapse transmission. Further, after receiving hypoxia, NMDA receptor may be inactivated with a lapse of time. This may contribute to protect fetal brain from an excess of Ca2+influx. Less
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