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 language | English |
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Pages (from-to) | 1508-1512 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 36 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2016 |
Keywords
- Nitric oxide
- stroke
- excitotoxicity
- experimental
- free radicals