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. 2002 Dec;22(5-6):827–834. doi: 10.1023/A:1021877512519

Treatment with 7-Nitroindazole Enhances Kainic Acid Induced Cholinergic Neurotoxicity in the Rat Striatum: A Neuroprotective Role for Neuronal Nitric Oxide

Beatriz H Guevara 1,2,3, Ghislaine C Cespedes 1,2,3, Luigi X Cubeddu 2,3,✉
PMCID: PMC11533795  PMID: 12585700

Abstract

1. In this study we investigated the effect of 7-nitroindazole (7-NI), a preferential inhibitor of neuronal nitric oxide synthase (nNOS), on kainic acid (KA) induced neurotoxicity in rats. Choline acetyltransferase activity (CAT), a cholinergic marker, and histological changes were employed to assess neurotoxicity.

2. In control rats, the local intrastriatal injection of 0.5 μg of KA reduced CAT from 22.9 ± 2.2 to 14.7 ± 2.0 nmol/h/mg tissue ((38 ± 6)% reduction) (P < 0.001). Greater reductions in CAT were observed with 1 and 2 μg of KA ((70 ± 6)% and (80 ± 3)%, respectively). 7-NI aggravated KA-induced cholinergic and histological damage. KA reduced CAT by (68.2 ± 4)% in 7-NI-treated rats, by (38 ± 6)% in saline-treated controls, and by (41 ± 4)% in peanut-oil- (7-NI-vehicle-) treated rats (P = 0.0047).

3. After KA, CAT activity averaged 14.3 ± 2.0 in peanut-oil-treated rats and 7.9 ± 1.0 nmol/h/mg tissue in 7-NI- (peanut-oil-) treated rats (P = 0.015). Similarly to changes in CAT, 7-NI treatment aggravated KA-induced histological changes indicative of neuronal damage (acute ischemic neuronal changes, disorganization of myelinated fibers bundle, and vacuolation changes of the neuropil). Treatment with 7-NI was not associated with increased mortality.

4. Our findings suggest that neuronal NO plays a neuroprotective action on excitotoxicity.

Keywords: brain nitric oxide, kainic acid, 7-nitroindazole, striatum, neurotoxicity, cholinergic neurons

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