Aminoguanidine reduces brain lesion volume after cold injury in the rat

The aim of this study was to examine the effect of aminoguanidine (AG), whi ch is thought to be an inducible nitric oxide synthase (iNOS) inhibitor, on lesion volume induced by cold injury in the parietal cortex of the rat. Co ld lesion was induced by applying a precooled (-78 degrees C) copper cylind er (diameter: 3 mm) for 6 s to the intact dura. Lesion volume was determine d using the triphenyltetrazolium-chloride method after 24 h. Pretreatment ( 1 h) and posttreatment (7.5 h) with AC; [10 or 100 mg/kg body mass (BM)] re duced the lesion volume by 15 and 27%, respectively. However, posttreatment alone with AG (10 and 100 mg/kg BM) caused less of a reduction in lesion v olume, by 8 and 20%, respectively. Pre- and posttreatment with AG also redu ced the plasma nitrate/nitrite concentration compared with lesioned, saline -treated rats. Only a double therapy with AG (100 mg/kg BM) resulted in a s ignificant reduction (48%) compared to saline alone, which was even larger (55%) compared to the sham group. The tissue nitrate/nitrite concentration was significantly attenuated by pre- and posttreatment with AG (100 mg/kg B M) not only in the ipsilateral but also in the contralateral hemisphere. Th ere was no difference regarding the parameter be tween shams and lesioned, saline-treated rats. Since combined pre- and posttreatment with AG reduced the lesion volume more than posttreatment alone and the plasma and tissue n itrate/nitrite concentrations were di minished during AG therapy compared t o shams, we hypothesize that AG inhibits not only iNOS but also other enzym es, such as nNOS, diamine oxidase, and advanced glycation endproducts synth ase.