NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage


Kleinschnitz C., Mencl S., Kleikers P. W. M. , Schuhmann M. K. , Lopez M. G. , Casas A. I. , ...More

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, vol.36, no.9, pp.1508-1512, 2016 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 9
  • Publication Date: 2016
  • Doi Number: 10.1177/0271678x16657094
  • Title of Journal : JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
  • Page Numbers: pp.1508-1512

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 invivo and invitro, but find three pharmacological post-synaptic density protein-95 inhibitors to be therapeutically ineffective.