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. , ...Daha Fazla

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, cilt.36, ss.1508-1512, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 36 Konu: 9
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1177/0271678x16657094
  • Dergi Adı: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
  • Sayfa Sayıları: ss.1508-1512

Özet

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.