Therapeutic Targets for Cerebral Ischemia Based on the Signaling Pathways of the GluN2B C Terminus

Sun, Yongjun; Zhang, Linan; You, Chun‐Xiang; Zhan, Liying

doi:10.1161/strokeaha.115.009314

Cited by 35 publications

(29 citation statements)

References 78 publications

(81 reference statements)

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“…Sun et al reported that NR2B was more lethal than those containing NR2A. Moreover, prodeath signaling pathways mediated by neuronal nitric oxide synthase (nNOS), phosphatase and tensin homolog located on chromosome 10 (PTEN), and calcium/calmodulin-dependent protein kinase II (CaMKII) have been linked to NR2B activation [ 59 ]. Therefore, the effects of the signaling pathways that activated NR2B are worthy of consideration.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Attenuates Cerebral Ischemia and Reperfusion Injury in Middle Cerebral Artery Occlusion of Rat via Modulation of Apoptosis, Inflammation, Oxidative Stress, and Excitotoxicity

Shen

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Electroacupuncture (EA) has several properties such as antioxidant, antiapoptosis, and anti-inflammatory properties. The current study was to investigate the effects of EA on the prevention and treatment of cerebral ischemia-reperfusion (I/R) injury and to elucidate possible molecular mechanisms. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. EA stimulation was applied to both Baihui and Dazhui acupoints for 30 min in each rat per day for 5 successive days before MCAO (pretreatment) or when the reperfusion was initiated (treatment). Neurologic deficit scores, infarction volumes, brain water content, and neuronal apoptosis were evaluated. The expressions of related inflammatory cytokines, apoptotic molecules, antioxidant systems, and excitotoxic receptors in the brain were also investigated. Results showed that both EA pretreatment and treatment significantly reduced infarct volumes, decreased brain water content, and alleviated neuronal injury in MCAO rats. Notably, EA exerts neuroprotection against I/R injury through improving neurological function, attenuating the inflammation cytokines, upregulating antioxidant systems, and reducing the excitotoxicity. This study provides a better understanding of the molecular mechanism underlying the traditional use of EA.

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Section: Discussionmentioning

confidence: 99%

Electroacupuncture Attenuates Cerebral Ischemia and Reperfusion Injury in Middle Cerebral Artery Occlusion of Rat via Modulation of Apoptosis, Inflammation, Oxidative Stress, and Excitotoxicity

Shen

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…In addition, PTEN plays an important role in limiting the synaptic function in the signaling through NMDA and AMPA receptors. This makes inhibition of PTEN a feasible molecular approach to revert neurological damage under pathological circumstances [ 139 , 140 , 141 , 142 , 143 , 144 ].…”

Section: Pten Inhibition By Small Molecules In Human Disease Theramentioning

confidence: 99%

PTEN Inhibition in Human Disease Therapy

Pulido

2018

Molecules

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The tumor suppressor PTEN is a major homeostatic regulator, by virtue of its lipid phosphatase activity against phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], which downregulates the PI3K/AKT/mTOR prosurvival signaling, as well as by its protein phosphatase activity towards specific protein targets. PTEN catalytic activity is crucial to control cell growth under physiologic and pathologic situations, and it impacts not only in preventing tumor cell survival and proliferation, but also in restraining several cellular regeneration processes, such as those associated with nerve injury recovery, cardiac ischemia, or wound healing. In these conditions, inhibition of PTEN catalysis is being explored as a potentially beneficial therapeutic intervention. Here, an overview of human diseases and conditions in which PTEN inhibition could be beneficial is presented, together with an update on the current status of specific small molecule inhibitors of PTEN enzymatic activity, their use in experimental models, and their limitations as research or therapeutic drugs.

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“…Neurotransmitter plays a critical role in the occurrence of ischemia cerebrovascular disease [7,8]. Some studies showed that during the process of brain ischemia, low neurotransmitter levels were found in hypothalamus, cerebral cortex and hippocampus, along with low neural activity, leading to cell apoptosis [9,10]. Hypoxia and insufficient perfusion caused intracellular Ca 2+ imbalance.…”

Section: Introductionmentioning

confidence: 99%

The effect of dexmedetomidine on GluR2 and NR2B expression of cortical neurons after cerebral ischemia-reperfusion in rats

Li¹,

Liu²

2018

biomedicalresearch

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Objective: Neurotransmitter plays a crucial role in ischemia cerebrovascular disease. Study has shown that Dexmedetomidine (Dex) contributes to neuroprotective functions. We thus observed the regulatory effect of Dex on the expressions of Glutamate Receptor-2 (GluR2) and N-Methyl-D-Aspartic Acid (NMDA) receptor 2B (NR2B) in cerebral cortical neurons with an ischemia-reperfusion rat model. Patients and methods: Healthy male SD rats were randomly divided into sham, model and Dex treatment groups (N=20 each). Whole-brain ischemia-reperfusion model was generated by the clipping of bilateral common carotid artery with hypotension. Dex (9 μg/kg) was infused immediately after reperfusion, while the other two groups received equal volume of saline. Morris water maze was employed to detect learning and memory function of rats. Brain tissues were extracted at 6, 24 and 72 h after reperfusion. Immunohistochemistry (IHC) was used to detect GluR2 and NR2B receptor levels, the mRNA levels of which were determined by real-time PCR. Results: The longer escape latency and fewer number of crossing platform in water maze were shown in Model rats group. Cortical GluR2 expression was down-regulated while NR2B level was increased. Dex treatment inhibited escape latency and increased crossing times, along with the rise of cortical GluR2 expression and reduction of NR2B expression (p<0.05) in a time-dependent manner (p<0.05). Conclusion: Dex could alleviate ischemia-reperfusion injury of rat brain via down-regulating GluR2 while increasing NR2B expression.

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Therapeutic Targets for Cerebral Ischemia Based on the Signaling Pathways of the GluN2B C Terminus

Cited by 35 publications

References 78 publications

Electroacupuncture Attenuates Cerebral Ischemia and Reperfusion Injury in Middle Cerebral Artery Occlusion of Rat via Modulation of Apoptosis, Inflammation, Oxidative Stress, and Excitotoxicity

Electroacupuncture Attenuates Cerebral Ischemia and Reperfusion Injury in Middle Cerebral Artery Occlusion of Rat via Modulation of Apoptosis, Inflammation, Oxidative Stress, and Excitotoxicity

PTEN Inhibition in Human Disease Therapy

The effect of dexmedetomidine on GluR2 and NR2B expression of cortical neurons after cerebral ischemia-reperfusion in rats

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