iNOS contribution to the NMDA-induced excitotoxic lesion in the rat striatum.

1 The aim of this study was to assess whether an excitotoxic insult induced by NMDA may induce an iNOS activity which contributes to the lesion in the rat striatum. 2 For this purpose, rats were perfused with 10 mM NMDA through a microdialysis probe implanted in the left striatum. Microdialysate nitrite content, striatal Ca-independent nitric oxide synthase activity and lesion volume were measured 48 h after NMDA exposure in rats treated with dexamethasone (DXM) (3 mg kg(-1) x 4) or aminoguanidine (AG) (100 mg kg(-1) x 4). 3 A significant increase in microdialysate nitrite content and in the Ca-independent NOS activity was observed 48 h after NMDA infusion. Both these increases were reduced by DXM and AG. The NMDA-induced striatal lesion was also reduced by both treatments. 4 Our results demonstrate that NMDA excitotoxic injury induces a delayed, sustained activation of a Ca-independent NOS activity. This activity is blocked by DXM and AGI strongly suggesting the involvement of iNOS. The fact that AG and DXM reduce the NMDA-elicited lesion suggests that iNOS contributes to the brain damage induced by excitotoxic insult.