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 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 9
  • Publication Date: 2016
  • Doi Number: 10.1177/0271678x16657094
  • Journal Name: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1508-1512
  • Keywords: Nitric oxide, stroke, excitotoxicity, experimental, free radicals, CEREBRAL-ISCHEMIA, GUANYLYL CYCLASE, STROKE, TRIAL
  • Middle East Technical University Affiliated: Yes

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.