This title appears in the Scientific Report : 2001 

Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia : evidence for direct and indirect mechanisms towards their resistance to neuropathology
Bidmon, H. J.
Emde, B. / Kowalski, T. / Schmitt, M. / Mayer, B. / Kato, K. / Asayama, K. / Witte, O. W. / Zilles, K.
Institut für Medizin; IME
Journal of chemical neuroanatomy, 22 (2001) S. 167 - 184
Amsterdam [u.a.] Elsevier Science 2001
167 - 184
Journal Article
Journal of Chemical Neuroanatomy 22
Please use the identifier: in citations.
Neuronal nitric oxide-I is constitutively expressed in approximate to2% of cortical interneurons and is co-localized with gamma -amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the, glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal peroxynitrite, H2O2-formation and caspase activation. (C) 2001 Elsevier Science B.V. All rights reserved.