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

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


Association analysis of Glutathione S-transferase omega-1 and omega-2 genetic polymorphisms and ischemic stroke risk in a Turkish population
Bilgin, Esra; Can Demirdöğen, Birsen; Ozcelik, Aysun Turkanoglu; Demirkaya, Seref; Adalı, Orhan (Informa UK Limited, 2019-01-01)
Objectives: Oxidative stress is a known risk factor for the pathogenesis of atherosclerosis, the main cause of ischemic stroke. Glutathione S-transferase (GST) omega-1 and omega-2, members of phase II enzymes, play a role in the antioxidant system. The single nucleotide polymorphisms (SNPs), C419A and A424G in GST omega genes can cause a decrease in enzyme activity. The aim of this study was to investigate the possible association between these polymorphisms and ischemic stroke risk in a Turkish population.
Dielectrophoretic detection of imatinib resistance in K562 Cells Using A lab-on-a-chip system
Demircan Yalçın, Yağmur; Toral, Taylan Berkın; Sukaş, Serkan; Yıldırım, Ender; Zorlu, Özge; Gündüz, Ufuk; Külah, Haluk (Chemical and Biological Microsystems Society (CBMS); 2019-10-27)
This study presents label-free detection of imatinib resistance in K562 cells via integrated dielectrophoretic detection and impedimetric counting on a lab-on-a-chip system. Two impedimetric counting units were placed upstream and downstream of dielectrophoretic detection unit to obtain differential cell count and consequently the trapping ratio. The trapping ratio up to 57% was achieved for imatinib resistant (~60-fold) K562 cells, while it was minimized to 20% for wild type K562 cells
Multielectrode venous catheter mapping as a high quality constraint for electrocardiographic inverse solution
Serinağaoğlu Doğrusöz, Yeşim; YILMAZ, BÜLENT; Brooks, DH (Elsevier BV, 2002-01-01)
A persistent challenge in solving inverse problems in electrocardiography is the application of suitable constraints to the calculation of cardiac sources. Whether one formulates the inverse problem in terms of epicardial potentials or activation wavefronts, the problem is physically ill-posed and hence results in numerically unstable computations. Suitable physiological constraints applied with appropriate weighting can recover useful inverse solutions. However, it is often difficult to determine the best ...
Simultaneous mapping of endocardium and epicardium from multielectrode intrachamber and intravenous catheters: a computer simulation-based validation
Baysoy, Engin; Cunedioglu, Ugur; Yilmaz, Buelent (Elsevier BV, 2010-01-01)
A multielectrode basket-shaped contact catheter (MBC) provides simultaneous recordings of unipolar or bipolar electrograms from within the heart chambers Another catheter-based mapping approach uses the multielectrode intravenous catheters (MIVCs), which are widely used to diagnose and treat supraventricular arrhythmias It is also known that mapping techniques are usually limited to one surface at a time Therefore, an approach that can be used for simultaneous mapping of left and right endocardial surfaces ...
Rapid ionic liquid-supported nano-hybrid composite reinforced hollow-fiber electromembrane extraction followed by field-amplified sample injection-capillary electrophoresis: An effective approach for extraction and quantification of Imatinib mesylate in human plasma
Forough, Mehrdad; Farhadi, Khalil; Eyshi, Ali; Molaei, Rahim; Khalili, Hedayat; Kouzegaran, Vahid Javan; Matin, Amir Abbas (2017-09-01)
The focus of this study is development of a new, convenient, rapid and sensitive electromembrane extraction approach (based on an ionic liquid-supported MWCNTs/ZnO reinforced hollow fiber, for the first time) as an off-line sample clean-upipreconcentration method coupled with capillary electrophoresis (CE-UV) using field-amplified sample injection (FASI) for quantification of Imatinib mesylate in human plasma. The nano-hybrid sorbent, coated by 1-octyl-3-methylimidazolium bromide ionic liquid (E0M1m]Br) in ...
Citation Formats
C. Kleinschnitz et al., “NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage,” JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, pp. 1508–1512, 2016, Accessed: 00, 2020. [Online]. Available: