Nitric oxide synthase and cytochrome c oxidase changes in the tumoural and peritumoural cerebral cortex.

Abstract

We analysed changes in nitric oxide synthase (NOS) and cytochrome oxidase (CO) activities in the tumoural and peritumoural cerebral cortex in order to investigate: a) the role of NO in tumourigenesis, in TBF regulation, and in vasogenetic PBE; b) the metabolic changes caused by the neoplasm in the surrounding tissues. Intra-operative samples of cerebral cortex were studied by means of immunohistochemistry for nNOS and iNOS, and by histochemistry for NADPH-diaphorase (NADPH-d) and CO. In contrast with normal cortex, reactive glial cells and the endothelium of small blood vessels displayed strong NADPH-d and iNOS activities in oedematous peritumoural tissue. In the tumoural cortex, NADPH-d and nNOS-positive neurones were reduced in number and their dendrites were thin and interrupted, and infiltrates of NADPH-d and iNOS-positive tumoural cells were frequent. CO activity was decreased in the deep layers of peritumoural cortex, and it was almost absent in the tumoural cortex. In peritumoural and tumoural cortex changes in NOS and CO activities suggest that the coupling between neuronal activity and blood flow is impaired in the damaged cerebral cortex, and that the increase in NOS activity may play a role in tumour vascularization and progression.