Study of therapeutic efficacy of the specific sigma-receptor ligand on brain injury following transient focal cerebral ischemia.

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671713
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: AKITA UNIVERSITY (1997); University of Tsukuba (1996)
• Principal Investigator: NISHIKAWA Toshiaki Akita University School of Medicine, Professor, 医学部, 教授 (50156048)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Kenji Yoshitomi Pharmaceutical Co., Ltd., 1st Research Institute of Drug Development,, 創薬第一研究所主任, 研究職 ; TAKAHASHI Hiroshi Tsuchiura Kyodo Hospital, Department of Anesthesia and Critical Care Medicine, C, 麻酔科長, 研究職 ; SATO Shigehito University of Tsukuba, Institute of Clinical Medicine, Associate Professor, 臨床医学系, 助教授 (30143176)
• Project Period (FY): 1996 – 1997
• Keywords: Focal cerebral ischemia / Neuronal damage / sigma-receptor / Pentazocine

Research Abstract

1996
Rats underwent focal cerebral ischemia using the filament occlusion technique for 2h, followed by 22h of reperfusion. Rats received saline or 1mol/kg per hour 4-phenyl-1- (4-phenylbutyl) piperidine (PPBP), the potent sigma-receptor ligand, by continuous intravenous infusion starting 1 h after the initiation of ischemia and continuing through 22h of reperfusion. Triphenyltetrazolium-determined infarction volume of ipsilateral striatum (PPBP,19(]SY.+-。[)4 mm<@D13@>D1, mean(]SY.+-。[)SEM) was smaller in rats treated with PPBP than in control (44(]SY.+-。[)4 mm<@D13@>D1) rats. However, because of variability within groups, the effect of PPBP to reduce total ipsilateral cortex infarction volume (PPBP,80(]SY.+-。[)28 mm<@D13@>D1 ; saline, 136(]SY.+-。[)27mm<@D13@>D1) did not reach statistical significance.
1997
Rats underwent focal cerebral ischemia using the filament occlusion technique for 2h, followed by 22h of reperfusion. Rats received (+) or (-)-pentazocine at a dose of 2mg/kg/h by continuous intravenous infusion from 1 h of ischemia to 22h of reperfusion. Triphenyltetrazolium-determined infarction volume of ipsilateral striatum ([+]-pentazocine, 19(]SY.+-。[)4mm<@D13@>D1 ; [-]-pentazocine, 44(]SY.+-。[)5mm<@D13@>D1) and cerebral cortex ([+]-pentazocine, 26(]SY.+-。[)12mm<@D13@>D1 ; [-]-pentazocine, 134(]SY.+-。[)29mm<@D13@>D1) was smaller in rats treated with (+) compared with (-)-pentazocine. Infarction volume in rats treated with (-)-pentazocine was also very similar to the infarction volume in saline-treated control rats from our previous study. These data indicate that sigma<@D21@>D2-receptors may play an important role in the mechanism of injury both in cortex and striatum after 2h of transient focal ischemia in rats.