Prolonged suppression of brain nitric oxide synthase activity by 7-nitroindazole protects against cerebral hypoxic-ischemic injury in neonatal rat

Akira Ishida, William H. Trescher, Mary S. Lange, Michael V. Johnston

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Nitric oxide mediates glutamate-induced excitotoxicity associated with cerebral hypoxia-ischemia through production in the brain by several isoforms of nitric oxide synthase (NOS). We examined the influence of the selective neuronal NOS inhibitor, 7-nitroindazole (7-NI), on brain NOS activity and its neuroprotective effects against cerebral hypoxic-ischemic injury in the postnatal day (PND) 7 rat. In the first set of experiments, 7-NI (50 mg/kg) administered intraperitoneally (i.p.) transiently inhibited NOS activity to 40% below the vehicle control level at 1 h after injection (P < 0.001, analysis of variance (ANOVA)). In contrast, 7-NI (100 mg/kg, i.p.) inhibited NOS activity to 56% below the control level at 1 h with prolonged suppression of NOS activity at 3, 6, 9 and 12 h after injection. Two-factor ANOVA revealed an overall effect on NOS activity of 7-NI treatment (P < 0.001) and time after injection (P < 0.001). In the second set of experiments, 7-NI (50, 100 mg/kg) or an equal volume of vehicle was administered after unilateral carotid artery ligation, but 30 min before hypoxia in PND 7 rats. 7-NI (100 mg/kg) significantly protected against cerebral hypoxic-ischemic injury (100 mg/kg of 7-NI, 1.7 ± 1.0% damage; control, 8.7 ± 1.6%,P < 0.05). 7-NI administered 15 min after cerebral hypoxia-ischemia was not neuroprotective. The data suggest that the protective effect of 7-NI is dose dependent, and is related to the duration of suppressed NOS activity.

Original languageEnglish (US)
Pages (from-to)349-354
Number of pages6
JournalBrain and Development
Volume23
Issue number5
DOIs
StatePublished - Aug 22 2001

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Prolonged suppression of brain nitric oxide synthase activity by 7-nitroindazole protects against cerebral hypoxic-ischemic injury in neonatal rat'. Together they form a unique fingerprint.

Cite this