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Neuronal expression of inducible nitric oxide synthase after oxygen and glucose deprivation in rat forebrain slices


, : Neuronal expression of inducible nitric oxide synthase after oxygen and glucose deprivation in rat forebrain slices. European Journal of Neuroscience 10(2): 445-456, Feb

Nitric oxide (NO) overproduction has been postulated to contribute significantly to ischaemia-reperfusion neurotoxicity. Inducible or type 11 NO synthase (NOS) synthesizes NO in large quantities for long periods of time. Therefore we investigated the expression and localization of iNOS after oxygen and glucose deprivation in rat forebrain slices. In this experimental model, calcium-independent NOS activity reached a maximum 180 min after the end of a 20 min oxygen-glucose deprivation period. During the same period of time, the calcium-independent activity was absent in control forebrain slices. To test whether this calcium-independent NOS activity was due to the expression of iNOS, the effects of the addition of dexamethasone, cycloheximide and pyrrolidine dithiocarbamate were determined. All of them inhibited the induction of the calcium-independent NOS activity measured in the rat forebrain slices after oxygen and glucose deprivation. Furthermore, oxygen and glucose deprivation caused the expression of the gene encoding iNOS in rat forebrain slices, as assessed by the detection of iNOS message and protein in these samples. A sixfold increase in the iNOS mRNA levels was observed at 180 min and the time-course of the expression of iNOS mRNA was in agreement with the temporal profile of iNOS enzymatic activity. Immunohistochemistry analysis revealed that iNOS was highly expressed in neurones, astrocytes and microglial cells. These results demonstrate for the first time that iNOS is expressed in neurones after oxygen and glucose deprivation, and that this expression occurs in short periods of time. These findings suggest that NO can play an important pathogenic role in the tissue damage that occurs after cerebral ischaemia.

US$19.90

PMID: 9749707

DOI: 10.1046/j.1460-9568.1998.00028.x


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