Different roles of neuronal and endothelial nitric oxide synthases on ischemic nitric oxide production in gerbil striatum

Adachi, Naoto; Lei, Baiping; Soutani, Masao; Arai, T.

doi:10.1016/s0304-3940(00)01222-2

Cited by 26 publications

(25 citation statements)

References 15 publications

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“…Our observations are in correlation with recent studies confirming that neuronal and endothelial NO synthases make different contributions to the postischemic NO production. The findings from the striatum suggest that the increased NO production after short duration of ischemia is derived mainly from nNOS and partly from eNOS, while NO production after a long duration of ischemia is induced by eNOS (Adachi et al, 2000).…”

Section: Discussionmentioning

confidence: 91%

“…Numerous transmitters are activated after the ischemic event. Recent studies have confirmed the involvement of nitric oxide (NO) and different nitric oxide synthase (NOS) isoforms in focal cerebral ischemia (Samdani et al, 1997;Adachi et al, 2000). Large amounts of NO produced during periods of cerebral ischemia mediate neuronal injury in various forms of stroke (Christopherson and Bredt, 1997).…”

Section: Introductionmentioning

confidence: 96%

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The Effect of Long-Term Reduction of Aortic Blood Flow on Spinal Cord Gray Matter in the Rabbit. Histochemical Study of NADPH-Diaphorase

et al. 2006

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1. The aim of this work was to study the influence of reduced aortic blood flow on NADPH-diaphorase (NADPH-d) staining in the gray matter of L4-S3 spinal cord segments. 2. Surgery was performed on the abdominal aorta of the rabbit. Spinal cord ischemia was introduced by infrarenal aortic constriction to 30% from the normal blood flow. Animals were allowed to survive 1 week, 1 month and 3 months after surgery. Neurological outcome was studied in relation to the duration of aortic occlusion. The NADPH-d histochemistry was used for the visualisation of spinal cord sections. 3. The most affected area of the spinal cord was pericentral region, and slight changes were seen in the NADPH-d activities of both dorsal and ventral horns. One week after surgery, NADPH-d positive pericentral neurons were almost unchanged in their shape and intensity of staining, the only difference was seen in slightly increased staining of the background around the central canal. One month following surgery neurons exhibited shrinkage or were swollen, NADPH-d staining was less intensive in the pericentral zone and positively stained vessels were present. 4. Three months of ischemia influenced the NADPH-d activity: (a) In the pericentral region were seen intensively NADPH-d stained neurons almost normal in shape of their bodies but with shortened processes or without them; (b) NADPH-d staining of neuropil was greatly enhanced mostly around the central canal and in the dorsal commissure; (c) Numerous vessels were present in the pericentral zone and in the location of the ventral horn. 5. It can be concluded that the reduction of blood flow in the abdominal aorta makes most changes in the pericentral region of the rabbit spinal cord. Increased NADPH-d staining of neuropil and the presence of positively stained vessels reflect increased NADPH-d/NOS production in the spinal cord gray matter after long-term incomplete aortic occlusion.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 96%

The Effect of Long-Term Reduction of Aortic Blood Flow on Spinal Cord Gray Matter in the Rabbit. Histochemical Study of NADPH-Diaphorase

et al. 2006

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“…This is expected to place the enzyme in a state refractory to direct activation by Ca 2ϩ . NO production has been measured by different methods, including electron paramagnetic resonance (EPR) (Tominaga et al, 1993;Wei et al, 1999), microdialysis (Adachi et al, 2000;Fassbender et al, 2000), and with microsensor probes (Lin et al, 1996;Stingele et al, 1998). Studies with microsensors observed variable concentrations of NO, whereas the readings from microdialysis or EPR studies have been difficult to translate into brain NO concentrations.…”

Section: Sequential Stimulatory and Inhibitory Phosphorylationsmentioning

confidence: 99%

Biphasic Coupling of Neuronal Nitric Oxide Synthase Phosphorylation to the NMDA Receptor Regulates AMPA Receptor Trafficking and Neuronal Cell Death

Rameau¹,

Tukey²,

Garcin³

et al. 2007

J. Neurosci.

148

130

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Postsynaptic nitric oxide (NO) production affects synaptic plasticity and neuronal cell death. Ca 2ϩ fluxes through the NMDA receptor (NMDAR) stimulate the production of NO by neuronal nitric oxide synthase (nNOS). However, the mechanisms by which nNOS activity is regulated are poorly understood. We evaluated the effect of neuronal stimulation with glutamate on the phosphorylation of nNOS. We show that, in cortical neurons, a low glutamate concentration (30 M) induces rapid and transient NMDAR-dependent phosphorylation of S1412 by Akt, followed by sustained phosphorylation of S847 by CaMKII (calcium-calmodulin-dependent kinase II). We demonstrate that phosphorylation of S1412 by Akt is necessary for activation of nNOS by the NMDAR. nNOS mutagenesis confirms that these phosphorylations respectively activate and inhibit nNOS and, thus, transiently activate NO production. A constitutively active (S1412D), but not a constitutively repressed (S847D) nNOS mutant elevated surface glutamate receptor 2 levels, demonstrating that these phosphorylations can control AMPA receptor trafficking via NO. Notably, an excitotoxic stimulus (150 M glutamate) induced S1412, but not S847 phosphorylation, leading to deregulated nNOS activation. S1412D did not kill neurons; however, it enhanced the excitotoxicity of a concomitant glutamate stimulus. We propose a swinging domain model for the regulation of nNOS: S1412 phosphorylation facilitates electron flow within the reductase module of nNOS, increasing nNOS sensitivity to Ca 2ϩ -calmodulin. These findings suggest a critical role for a kinetically complex and novel series of regulatory nNOS phosphorylations induced by the NMDA receptor for the in vivo control of nNOS.

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“…As a result of the multiple and contradictory actions of NO as well as the different sources of NO synthase (NOS), modulations of NO in ischemic brain have been shown to produce a variety of outcomes [6]. Both neuronal NOS (nNOS) and inducible NOS (iNOS) activities have been proposed to be detrimental to the ischemic brain, whereas endothelial NOS (eNOS) activity might be protective [7][8][9]. However, little information is available on the contributions of the three isoforms of NOS to the ischemic brain in details, for example, the exact working time window and how the concentration changes.…”

Section: Introductionmentioning

confidence: 99%

The dynamic detection of NO during stroke and reperfusionin vivo

Liu

Zhang

et al. 2009

Brain Injury

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Different roles of neuronal and endothelial nitric oxide synthases on ischemic nitric oxide production in gerbil striatum

Cited by 26 publications

References 15 publications

The Effect of Long-Term Reduction of Aortic Blood Flow on Spinal Cord Gray Matter in the Rabbit. Histochemical Study of NADPH-Diaphorase

The Effect of Long-Term Reduction of Aortic Blood Flow on Spinal Cord Gray Matter in the Rabbit. Histochemical Study of NADPH-Diaphorase

Biphasic Coupling of Neuronal Nitric Oxide Synthase Phosphorylation to the NMDA Receptor Regulates AMPA Receptor Trafficking and Neuronal Cell Death

The dynamic detection of NO during stroke and reperfusionin vivo

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