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, sa.9, ss.1508-1512, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 9
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1177/0271678x16657094
  • Dergi Adı: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1508-1512
  • Anahtar Kelimeler: Nitric oxide, stroke, excitotoxicity, experimental, free radicals, CEREBRAL-ISCHEMIA, GUANYLYL CYCLASE, STROKE, TRIAL
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

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.