| Project/Area Number |
13671585
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Yamaguchi University |
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Principal Investigator |
MATSUMOTO Mishiya Yamaguchi Univ. Hospital, Assistant Professor, 医学部附属病院, 講師 (60243664)
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| Co-Investigator(Kenkyū-buntansha) |
SAKABE Takefumi Yamaguchi Univ. School of Medicine, Professor, 医学部, 教授 (40035225)
FUKUDA Shirou Yamaguchi Univ. Hospital, Research Associate, 医学部附属病院, 助手 (70322245)
IIDA Yasuhiko Yamaguchi Univ. Hospital, Research Associate, 医学部附属病院, 助手 (90304485)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Neurotoxicity / local anesthetics / glutamate / apoptosis / oligodendrocyte / rabbit / 脊椎麻酔 / 脊髄 |
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| Research Abstract |
High concentrations of local anesthetics have been known to be neurotoxic. However, the mechanism for their neurotoxicity Is obscure. We have reported that high concentrations of tetracaine administered intrathecally in the spinal cord increase glutamate concentrations and cause neuronal injury in a dose dependent manner. We investigated whether this is true in other local anesthetics and whether an AMPA receptor antagonist (YM872) can reduce neuronal injury caused by high concentrations of local anesthetics.
Lidocaine (10%) , tetracaine (2%), bupivacaine (2%), and ropivacaine (2%) were administered intrathecally at the cauda equina level to the rabbits implanted with an intrathecal microdialysis probe at the lumbar spinal cord level. Glutamate concentrations in the lumbar spinal cord level were monitored by microdialysis. Neurologic and histologic assessment was done one week after the administration. The peak concentrations of glutamate after lidocaine, tetracaine, bupivacaine, and ropivacaine were 10-fold, 6-fold, 5-fold, and 2.5-fold greater than baseline values, respectively. The degree of neuronal injury was in order of lidocaine > tetracaine > bupivacaine > ropivacaine.
Intrathecal administration of YM872 tended to reduce sensory and motor function at one week after administration of tetracaine. A chromatolytic change of the motor neuron caused by tetracaine was attenuated by YM872.
These results suggest that increased concentrations of glutamate in the cerebrospinal fluid is the common p phenomenon after intrathecal administration of local anesthetics and that glutamate plays, at least in part, an role in the mechanism of neurotoxicity by local anesthetics
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