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DEVELOPMENT OF NEUROPROTECTIVE STRATEGY BY THE COMBINATION THERAPY OF IMMUNOSUPPRESANT AND NEURONAL NITRIC OXIDE INHIBITOR ADMINISTRATION AGAINST NEONATAL BRAIN DAMAGE.

Research Project

Project/Area Number 15591135
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTokyo Medical University

Principal Investigator

TAKEI Yukito  Tokyo Medical University, Medicine, Lecturer, 医学部, 講師 (20256259)

Co-Investigator(Kenkyū-buntansha) TAKAMI Takeshi  Tokyo Medical University, Medicine, Clinical assistant, 医学部, 助手 (20287147)
SAITOH Tetsuya  Tokyo Medical University, Medicine, Clinical assistant, 医学部, 助手 (10384968)
立花 真紀  東京医科大学, 医学部, 助手 (60349470)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordshypoxic-ischemic brain damage / FK506 / 7-nitroindazole / neuroprotection / dose dependency / therapeutic time window / combination therapy / neonate / 7-nitroindazole / 低酸素性虚血性脳症 / Cycrosporin A / 脳保護
Research Abstract

The goal of this study was to investigate the clinical neuroprotective strategy by means of the combination therapy of immunosuppressant, FK506, and the neuronal nitric oxide inhibitor, 7-nitroindazole, administration against hypoxic-ischemic (HI) brain damage in neonatal rats. We also investigated the dose dependency and therapeutic time window of FK506 against neonatal brain damage due to hypoxia-ischemia. The rats were performed by the transient occlusion of left carotid artery and the exposure to 8 % oxygen (HI) for 90 min. Then the brains were histologically examined 24 hrs after the HI. The HI insult induced the admixtures of the following neuronal damages; piknosis, eosinophilic change, karyorrhexis, loss of neurons, caspase 3-positive cells, spongy degeneration, and/or cystic change with macrophages in the hippocampus, frontal and temporal cortices, and/or basal ganglia. The severity of the brain damage was estimated by the extent of the damaged neurons in the brain, using the brain damage scores. The treatment of 2 mg/kg FK506 (high dose), but not 1 mg/kg (low dose), immediately after HI insult demonstrated significant decreases in the severity of the neuronal damage and caspase-3 activation 24 h after the insult, compared with vehicle injection (dose dependency). The treatment of 2 mg/kg FK506 immediately and 30 min after HI insult, but not 60 min after, demonstrated significant neuroprotective effect, compared with vehicle injection (therapeutic time window). The combination therapy of 1 mg/kg (low dose) FK506 and 7-nitroindazole demonstrated significantly more neuroprotetive effect than the single usage of either FK506 or 7NI.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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