NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage. Issue 9 (September 2016)

• Record Type: Journal Article
• Authors: Kleinschnitz, Christoph; Mencl, Stine; Kleikers, Pamela WM; Schuhmann, Michael K; G López, Manuela; Casas, Ana I; Sürün, Bilge; Reif, Andreas; Schmidt, Harald HHW
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 36:Issue 9(2016)
• Page Start: 1508
• Page End: 1512
• Publication Date: 2016-09
• Subjects: Nitric oxide -- stroke -- excitotoxicity -- experimental -- free radicals; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X16657094
• Languages: English
• ISSNs: 0271-678X

Abstract

Promising results have been reported in preclinical stroke target validation for pharmacological principles that disrupt the N-methyl-D-aspartate receptor–post-synaptic density protein-95–neuronal nitric oxide synthase complex. However, post-synaptic density protein-95 is also coupled to potentially neuroprotective mechanisms. As post-synaptic density protein-95 inhibitors may interfere with potentially neuroprotective mechanisms and sufficient validation has often been an issue in translating basic stroke research, we wanted to close that gap by comparing post-synaptic density protein-95 inhibitors with NOS1 −/− mice and a NOS inhibitor. We confirm the deleterious role of NOS1 in stroke both in vivo and in vitro, but find three pharmacological post-synaptic density protein-95 inhibitors to be therapeutically ineffective.