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

Christoph Kleinschnitz*, Stine Mencl, Pamela W. M. Kleikers, Michael K. Schuhmann, Manuela G. Lopez, Ana I. Casas, Bilge Surun, Andreas Reif, Harald H. H. W. Schmidt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.
Original languageEnglish
Pages (from-to)1508-1512
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number9
DOIs
Publication statusPublished - Sep 2016

Keywords

  • Nitric oxide
  • stroke
  • excitotoxicity
  • experimental
  • free radicals

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