Effects of aminoguanidine on cerebral ischemia in mice: comparison between mice with and without inducible nitric oxide synthase gene

Abstract

The expression of inducible nitric oxide synthase (iNOS) is induced in the late stage of cerebral ischemia, and NO produced by iNOS contributes to delays in recovery from brain neuronal damage. To examine the importance of iNOS in the above process, we compared the effects of aminoguanidine (AG), selective iNOS inhibitor, on infarct volume and neurological deficit in iNOS null mice and normal mice subjected to brain ischemia. Neurological deficits in iNOS null mice at 24 h post-ischemia were mild compared with those of normal mice, and did not improve by AG treatment at 96 h post-ischemia. The mean infarct volume of iNOS null mice was smaller than that of normal mice at 96 h post-ischemia, and was not influenced by AG treatment. In contrast, AG reduced the infarct volume in normal mice to levels similar to those of saline-treated iNOS null mice at 96 h post-ischemia. Our results indicated that AG suppresses iNOS activity in mice with brain ischemia to level equivalent to those seen in iNOS knockout mice, confirming that this enzyme is involved in ischemic brain injury.