Inducible nitric oxide synthase expression in human cerebral infarcts

The inducible or "immunological" isoform of nitric oxide synthase (iNOS) is induced in many cell types by inflammatory stimuli and synthesizes toxic a mounts of NO. In rodent models of focal cerebral ischemia, iNOS is expresse d in neutrophils invading the injured brain and in local blood vessels. Stu dies with iNOS inhibitors and iNOS null mice indicate that NO produced by i NOS contributes to ischemic brain injury. In the present study, we sought t o determine whether iNOS is also expressed in the human brain after ischemi c stroke. Studies were conducted using immunohistochemistry on autopsy brai ns with neuropathological evidence of acute cerebral infarction. iNOS immun oreactivity was observed in neutrophils infiltrating the ischemic brain and in blood vessels within the ischemic territory. iNOS-positive cells also w ere immunoreactive for nitrotyrosine, reflecting protein nitration by NO-de rived peroxynitrite and nitrites. iNOS or nitrotyrosine immunoreactivity wa s not detected outside the region of the infarct. These observations provid e evidence that iNOS is expressed in the human brain after ischemic infarct ion and support the hypothesis that iNOS inhibitors may be useful in the tr eatment of ischemic stroke in humans.