scholarly journals cGMP Imaging in Brain Slices Reveals Brain Region-Specific Activity of NO-Sensitive Guanylyl Cyclases (NO-GCs) and NO-GC Stimulators

2018 ◽  
Vol 19 (8) ◽  
pp. 2313 ◽  
Author(s):  
Stefanie Peters ◽  
Michael Paolillo ◽  
Evanthia Mergia ◽  
Doris Koesling ◽  
Lea Kennel ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Brain Region ◽  
Specific Activity ◽  
Brain Slices ◽  
Specific Effect ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Cgmp Signaling ◽  
Ca1 Area ◽  
The Brain

Impaired NO-cGMP signaling has been linked to several neurological disorders. NO-sensitive guanylyl cyclase (NO-GC), of which two isoforms—NO-GC1 and NO-GC2—are known, represents a promising drug target to increase cGMP in the brain. Drug-like small molecules have been discovered that work synergistically with NO to stimulate NO-GC activity. However, the effects of NO-GC stimulators in the brain are not well understood. In the present study, we used Förster/fluorescence resonance energy transfer (FRET)-based real-time imaging of cGMP in acute brain slices and primary neurons of cGMP sensor mice to comparatively assess the activity of two structurally different NO-GC stimulators, IWP-051 and BAY 41-2272, in the cerebellum, striatum and hippocampus. BAY 41-2272 potentiated an elevation of cGMP induced by the NO donor DEA/NO in all tested brain regions. Interestingly, IWP-051 potentiated DEA/NO-induced cGMP increases in the cerebellum and striatum, but not in the hippocampal CA1 area or primary hippocampal neurons. The brain-region-selective activity of IWP-051 suggested that it might act in a NO-GC isoform-selective manner. Results of mRNA in situ hybridization indicated that the cerebellum and striatum express NO-GC1 and NO-GC2, while the hippocampal CA1 area expresses mainly NO-GC2. IWP-051-potentiated DEA/NO-induced cGMP signals in the striatum of NO-GC2 knockout mice but was ineffective in the striatum of NO-GC1 knockout mice. These results indicate that IWP-051 preferentially stimulates NO-GC1 signaling in brain slices. Interestingly, no evidence for an isoform-specific effect of IWP-051 was observed when the cGMP-forming activity of whole brain homogenates was measured. This apparent discrepancy suggests that the method and conditions of cGMP measurement can influence results with NO-GC stimulators. Nevertheless, it is clear that NO-GC stimulators enhance cGMP signaling in the brain and should be further developed for the treatment of neurological diseases.

scholarly journals Protective Effects of a New C-Jun N-terminal Kinase Inhibitor in the Model of Global Cerebral Ischemia in Rats

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1722 ◽  
Author(s):  
Mark B. Plotnikov ◽  
Galina A. Chernysheva ◽  
Oleg I. Aliev ◽  
Vera I. Smol’iakova ◽  
Tatiana I. Fomina ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cerebral Ischemia ◽  
Endothelial Dysfunction ◽  
Neurological Deficit ◽  
Neuroprotective Effect ◽  
Global Cerebral Ischemia ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area ◽  
The Brain

c-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5′-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S. The experiments were performed in a rat model of ischemic stroke with three-vessel occlusion (model of 3VO) affecting the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. After 7-min episode of GCI in rats, 25% of animals died, whereas survived animals had severe neurological deficit at days 1, 3, and 5 after GCI. At day 5 after GCI, we observing massive loss of pyramidal neurons in the hippocampal CA1 area, increase in lipid peroxidation products in the brain tissue, and decrease in local cerebral blood flow (LCBF) in the parietal cortex. Moreover, blood hyperviscosity syndrome and endothelial dysfunction were found after GCI. Administration of IQ-1S (intragastrically at a dose 50 mg/kg daily for 5 days) was associated with neuroprotective effect comparable with the effect of citicoline (intraperitoneal at a dose of 500 mg/kg, daily for 5 days).The neuroprotective effect was accompanied by a decrease in the number of animals with severe neurological deficit, an increase in the number of animals with moderate degree of neurological deficit compared with control GCI group, and an increase in the number of unaltered neurons in the hippocampal CA1 area along with a significant decrease in the number of neurons with irreversible morphological damage. In rats with IQ-1S administration, the LCBF was significantly higher (by 60%) compared with that in the GCI control. Treatment with IQ-1S also decreases blood viscosity and endothelial dysfunction. A concentration-dependent decrease (IC50 = 0.8 ± 0.3 μM) of tone in isolated carotid arterial rings constricted with phenylephrine was observed after IQ-1S application in vitro. We also found that IQ-1S decreased the intensity of the lipid peroxidation in the brain tissue in rats with GCI. 2.2-Diphenyl-1-picrylhydrazyl scavenging for IQ-1S in acetonitrile and acetone exceeded the corresponding values for ionol, a known antioxidant. Overall, these results suggest that the neuroprotective properties of IQ-1S may be mediated by improvement of cerebral microcirculation due to the enhanced vasorelaxation, beneficial effects on blood viscosity, attenuation of the endothelial dysfunction, and antioxidant/antiradical IQ-1S activity.

Transplantation of neural progenitor cells stimulates endogenous neurogenesis in mice after ischemic stroke

2014 ◽  
Vol 2 (1) ◽  
pp. 85-89 ◽  
Author(s):  
O. Tsupykov ◽  
V. Kyryk ◽  
A. Mamchur ◽  
P. Poberezhnyi ◽  
G. Butenko ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Brain Slices ◽  
Neural Progenitor ◽  
Short Term ◽  
Hippocampal Ca1 ◽  
Ca1 Area ◽  
Adaptation Processes ◽  
The Brain

The researchers have currently been actively investigating the possibilities for transplantation of the stem cells of various sources for treatment of the ischemic and degenerative diseases of the nervous systemInfluence of transplantation of the hippocampal neural progenitor cells (NPCs) on endogenous neurogenesis in the mice after brain ischemia-reperfusion induced by 20 min occlusion of both carotid arteries has been studied. Following 24 hours after occlusion the NPCsisolated from the hippocampus of the FVB-Cg-Tg(GFPU)5Nagy/J mice transgenic by the GFP gene were transplanted stereotactically into hippocampal CA1 area of the experimental animals. For evaluating neurogenesis in the hippocampus of the ischemic animals we used immunohistochemical staining of the brain slices for BrdU and doublecortin (DCX). It has been found that transplantation of neural progenitor cells increased the number of BrdU- and DCX-positive cells in the dentate gyrus of the hippocampus after short-term global ischemia.These data allow admit that NPC transplantation to the ischemic animals influences on endogenous adaptation processes in the brain and on the neurogenesis, in particular.

scholarly journals Propolis inhibited Bax expression and increased neuronal count of hippocampal area CA1 in rats receiving sodium nitrite

2019 ◽  
Vol 38 (2) ◽  
pp. 73
Author(s):  
Kuswati Kuswati ◽  
Ety Sari Handayani ◽  
Zainuri Sabta Nugraha ◽  
Fishella Aprista Rahmanti ◽  
Zulfikar Loka Wicaksana ◽  
...  
Keyword(s):  
Sodium Nitrite ◽  
Neuronal Damage ◽  
Control Group ◽  
Wistar Strain ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Hippocampal Area ◽  
Ca1 Area ◽  
The Brain ◽  
Antioxidant Effects

Background<br />Sodium nitrite induces hypoxia and oxidative stress in the hippocampus, decreasing the number of neurons in the hippocampus and cognitive function. Propolis contains chrysin that has antioxidant effects that are expected to inhibit neuronal damage in the hippocampus. This study aims to determine the effects of propolis on the expression Bcl-2-associated X protein (Bax) and the number of neurons in the rat hippocampus receiving sodium nitrite.<br /><br />Methods<br />This study of laboratory experimental design was conducted on 18 male Wistar strain rats (Rattus norvegicus), they were randomized into 3 groups: one control group (K) received sodium nitrite and two intervention groups  (P1 and P2) received sodium nitrite and propolis at doses of 100 and 200 mg/kgBW. Treatment with sodium nitrite and propolis were given for 60 days, followed by termination. The number of neurons and Bax expression in the hippocampal CA1 area were measured. One-way ANOVA was used to analyze the data.<br /><br />Results<br />There were significant differences in Bax expression between group K and groups P1 and P2 (p&lt;0.001). The lowest number of neurons in the hippocampal CA1 area was in the K group. There were significant differences in the number of neurons between control (K) group and groups P1 and P2 (p&lt;0.001).<br /><br />Conclusion<br />Propolis inhibited the expression of Bax and decreased the number of neurons in the hippocampal CA1 area of rats receiving sodium nitrite. This study provides information about the benefits of propolis as an antioxidant in the brain.

scholarly journals Pre-treated Populus tomentiglandulosa extract inhibits neuronal loss and alleviates gliosis in the gerbil hippocampal CA1 area induced by transient global cerebral ischemia

2017 ◽  
Vol 50 (4) ◽  
pp. 284 ◽  
Author(s):  
Joon Ha Park ◽  
Tae-Kyeong Lee ◽  
Ji Hyeon Ahn ◽  
Bich-Na Shin ◽  
Jeong Hwi Cho ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Loss ◽  
Global Cerebral Ischemia ◽  
Transient Global Cerebral Ischemia ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area

scholarly journals Oxytocin protects neurons from hypoxic-ischemic brain injury by enhancing inhibitory neurotransmission in neonatal rats

2021 ◽  
Vol 20 (9) ◽  
pp. 1909-1914
Author(s):  
Linhua Xiang ◽  
Rong Wu ◽  
Kangling Liu ◽  
Jing Wang
Keyword(s):  
Protective Effect ◽  
Hippocampal Slices ◽  
Time Lapse ◽  
Oxytocin Receptor ◽  
Neonatal Rats ◽  
Model Group ◽  
Ischemic Brain ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area

Purpose: To study the protective effect of oxytocin on hypoxic-ischemic brain neuron injury in neonatal rats, and the mechanism of action involved.Methods: Hippocampal slices from neonatal SD rats were cultured in oxygen/glucose-deprived (OGD) solution, leading to establishment of hypoxic-ischemic model of hippocampal slices in vitro. The slices were assigned to 3 groups: control (ACSF solution), model (OGD solution), and oxytocin (OGD solution + 1 μM oxytocin). The effect of oxytocin on vertebral neurons in hippocampal CA1 region of HIBD rats was determined using TOPRO-3 staining, while the effects of oxytocin on hypoxic depolarization (AD) and inhibitory postsynaptic currents (iPSCs) were measured by cell patch clamp technique.Results: The fluorescence intensity of vertebral lamina in hippocampal CA1 area of model group was significantly higher than that of control group, while the corresponding value for oxytocin group was significantly lower than that of model group (p < 0.05). The time lapse before occurrence of AD in hippocampal CA1 area was significantly longer in oxytocin group than in model group, while the time lapse before neuronal AD in oxytocin receptor antagonist group was lower than that in oxytocin group. The frequency and amplitude of iPSCs in oxytocin group were markedly higher than the corresponding control values.Conclusion: Oxytocin exerts protective effect against hypoxic-ischemic brain neuronal damage in neonatal rats by regulating the activation of oxytocin receptor and GABA receptor, and inhibiting nerve transmission. These findings may be of benefit in the development of a suitable therapy for HIBD.

Limited Effect of Neuritic Plaques on Neuronal Density in the Hippocampal CA1 Area of Alzheimer Patients

1998 ◽  
Vol 12 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Ahmad Salehi ◽  
Jan M. Bakker ◽  
Monique Mulder ◽  
Dick F. Swaab
Keyword(s):  
Neuritic Plaques ◽  
Limited Effect ◽  
Neuronal Density ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area

scholarly journals Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Fang Li ◽  
Chao-Qun Yan ◽  
Li-Ting Lin ◽  
Hui Li ◽  
Xiang-Hong Zeng ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Cognitive Deficits ◽  
Pyramidal Neuron ◽  
Neuron Number ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area
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