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.
Keywords
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Article info
Publication history
Accepted:
June 18,
2001
Received in revised form:
June 15,
2001
Received:
September 25,
2000
Identification
Copyright
© 2001 Elsevier Science Inc. Published by Elsevier Inc. All rights reserved.
