1992 Fiscal Year Final Research Report Summary
Effects of Excitatory Amino Acid Antagonists and Calcium Channel Blockers in the Treatment of Ischemic Brain Injury
| Project/Area Number |
03670729
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | Ehime University |
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Principal Investigator |
ARAI Tatsuru Ehime Univ., Sch. of Med., Professor, 医学部, 教授 (50033436)
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| Co-Investigator(Kenkyū-buntansha) |
YOROZUYA Toshihiro Ehime Univ., Hospital, Assistant Instructor, 医学部附属病院, 助手 (10230848)
KUZUME Koh Ehime Univ., Sch. of Med., Assistant Instructor, 医学部, 助手 (70161635)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Forebrain ischemia / Hippocampal CA1 cell / Barbiturate / Calcium channel blocker / NMDA receptor antagonist / AMPA receptor antagonist |
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| Research Abstract |
Increase in the levels of excitatory amino acid (EAA) in extracellular fluid and Ca^<2+> in neuronal cell may be playing an important role in the occurrence of neuronal cell injury after transient brain ischemia. This study was carried out to deter-mine the effects of EAA receptor antagonist, Ca^<2+> channel blocker and barbiturate on the process of brain cell injury after ischemia.
Materials and Methods: Fifty-three Mongolian gerbils were divided into 3 groups, sham, control and experimental. In experimental group one of following drugs was administered intraperitoneally 15 min before 3 min of forebrain ischemia by carotid occlusion; Pentobarbital 30 mg/kg, Ketamine 10 mg/kg, Benidipine 10, 30 and 50 micg/kg and MK801 4 mg/kg. NBQX 60 mg/kg was given immediately after ischemia in one group. In Pentobarbital group influences of 5 min ischemia was studied as well. During the ischemia brain temperature was kept at 37ﾟC strictly monitoring brain and rectal temperatures continuously. The brains were excised 1 week later and the grade of injury of hippocampal CA1 cells were examined microscopically. Results: In the control group CA1 cell injury as severe as in 5 min ischemia with ordinary ischemia method was observed. The groups in which Pentobarbital was given before ischemia and NBQX after ischemia were the only ones in the drug groups, which had significantly better results than control group. Discussion: That pretreatment with barbiturate is beneficial for ischemic cell injury has been well known and is confirmed in our study. Beneficial effect of NBQX, the AMPA receptor antagonist, was demonstrated as well but Benidipine, the voltage sensitive Ca^<2+> channel blocker, and MK801, the NMDA receptor antagonist, were not beneficial for the preservation of brain cells during ischemia. This indicates the importance of AMPA receptor in the process of ischemic brain cell injury.
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