Direct evidence for the role of nitric oxide on the glutamate-induced neuronal death in cultured cortical neurons

1998 ◽  
Vol 780 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Masanori Yamauchi ◽  
Keiichi Omote ◽  
Takafumi Ninomiya
Keyword(s):  
Nitric Oxide ◽  
Neuronal Death ◽  
Cortical Neurons ◽  
Direct Evidence ◽  
Cultured Cortical Neurons

An Na+/H+ exchanger inhibitor suppresses cellular swelling and neuronal death induced by glutamate in cultured cortical neurons

2003 ◽  
pp. 223-226 ◽  
Author(s):  
Seiji Yamamoto ◽  
Y. Matsumoto ◽  
Y. Suzuki ◽  
T. Tsuboi ◽  
S. Terakawa ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Cortical Neurons ◽  
Cultured Cortical Neurons ◽  
Cellular Swelling

In vivo location and mechanism of EDHF-mediated vasodilation in canine coronary microcirculation

1999 ◽  
Vol 277 (3) ◽  
pp. H1252-H1259 ◽  
Author(s):  
Yasuhiro Nishikawa ◽  
David W. Stepp ◽  
William M. Chilian
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Direct Evidence ◽  
Coronary Microcirculation ◽  
Combined Administration ◽  
Cytochrome P 450 ◽  
Coronary Arterioles

Responses of epicardial coronary arterioles to ACh were measured using stroboscopic fluorescence microangiography in dogs ( n = 38). ACh (0.1 and 0.5 μg ⋅ kg−1 ⋅ min−1ic) dilated small (<100 μm, 11 ± 2 and 19 ± 2%, respectively) and large (>100 μm, 6 ± 3 and 13 ± 3%, respectively) arterioles at baseline. Combined administration of N ω-monomethyl-l-arginine (l-NMMA; 1.0 μmol/min ic) and indomethacin (10 mg/kg iv) eliminated ACh-induced dilation in large coronary arterioles but only partially attenuated that in small arterioles. Suffusion of a buffer containing 60 mM KCl (high KCl) completely abolished cromakalim-induced dilation in arterioles and in combination with l-NMMA plus indomethacin completely blocked ACh-induced dilation in small arterioles. This indicated that the vasodilation to ACh that persists in small arterioles after administration of l-NMMA and indomethacin is mediated via a hyperpolarizing factor. The ACh-induced vasodilation remaining after l-NMMA and indomethacin was completely blocked by the large-conductance potassium-channel antagonist iberiotoxin or by epicardial suffusion of miconazole or metyrapone, inhibitors of cytochrome P-450 enzymes. These observations are consistent with the view that endothelium-derived hyperpolarizing factor (EDHF) is a product of cytochrome P-450 enzymes and produces vasodilation by the opening of large-conductance potassium channels. We conclude that ACh-induced dilation in large coronary arterioles is mediated mainly by nitric oxide (NO), whereas, in small arterioles both NO and EDHF mediate dilation to ACh. These data provide the first direct evidence for an in vivo role of EDHF in small coronary arterioles.

scholarly journals MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Xingping Qin
Keyword(s):  
Neuronal Death ◽  
Cortical Neurons ◽  
Detection System ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Neuroprotective Effects ◽  
Mortality And Morbidity ◽  
Microglial Polarization ◽  
Show Evidence ◽  
Cultured Cortical Neurons

Abstract INTRODUCTION Glycine is a nonessential amino acid with known neuroprotective effects. Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite extensive research, the treatment for SAH is limited. The present study was designed to investigate the role of glycine in neuroprotection following SAH. We have previously demonstrated that glycine is involved in neuroprotection in intracerebral hemorrhage via the PTEN/AKT signal pathway. However, whether it has a role in inducing neuroprotection following SAH is not known. METHODS We established the SAH model, evaluated the SAH grade, neurological scores, brain water content, glycine-mediated C (FJC) staining, cell viability and LDH release, and did cortical neuron and microglia culture. Treatment was conducted by intracerebroventricular injection. Cultured cortical neurons and cultured cortical microglia were treated with standard ECS for 60 min and then treated with glycine (100 μM) for 60 min. Cell replacement medium was used for subsequent experiments. vPCR was performed on the Opticon 2 real-time polymerase chain reaction (PCR) detection system using the corresponding primers and SYBR gene PCR master mix. RESULTS In this present study, we show evidence of glycine mediated amelioration of neuronal death and brain edema following SAH via a novel pathway. Following SAH there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), which is reversed with glycine treatment. We also found that glycine-regulated neuroprotection following SAH via AKT activation. Glycine was shown to down-regulate PTEN by up-regulating miRNA-26b, followed by activation of AKT, resulting in inhibition of neuronal death. Inhibition of AKT, PTEN depletion or suppression of miRNA-26b blocked the neuroprotective effect of glycine. Glycine treatment also suppresses SAH-induced M1 microglial polarization and promotes anti-inflammation, which indirectly inhibits neuronal death. CONCLUSION Glycine has neuroprotective effects in SAH injury and is mediated by the miRNA-26b/PTEN/AKT signal pathway, which may be a therapeutic target for treatment of SAH injury.

The AMPAR antagonist perampanel regulates neuronal necroptosis via Akt/GSK3β signaling after acute traumatic injury in cortical neurons

2020 ◽  
Vol 19 ◽  
Author(s):  
Tao Chen ◽  
Li-Kun Yang ◽  
Jie Zhu ◽  
Chun-Hua Hang ◽  
Yu-Hai Wang
Keyword(s):  
Traumatic Brain Injury ◽  
Protective Effect ◽  
Neuronal Death ◽  
Cortical Neurons ◽  
Therapeutic Potential ◽  
Traumatic Injury ◽  
Neuroprotective Effects ◽  
Stroke Models ◽  
Cultured Cortical Neurons

Background: Perampanel is a highly selective and non-competitive α-amino-3-hydroxy-5 -methyl-4-isoxazole propionate (AMPA) receptor (AMPAR) antagonist, which has been licensed as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was found to exert neuroprotective effects in hemorrhagic and ischemic stroke models. Objective: In this study, the protective effect of perampanel was investigated. Method: The protective effect of perampanel was investigated in an in vitro traumatic neuronal injury (TNI) model in primary cultured cortical neurons. Conclusion: Our present data suggest that necroptosis plays a key role in the pathogenesis of neuronal death after TNI, and that perampanel might have therapeutic potential for patients with traumatic brain injury (TBI).

Abstract 3629: Crucial Role of Nitric Oxide Synthases System in Endothelium-Dependent Hyperpolarization in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Aya Takaki ◽  
Keiko Morikawa ◽  
Yoshinori Murayama ◽  
Ender Tekes ◽  
Hiroto Yamagishi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Antihypertensive Treatment ◽  
Direct Evidence ◽  
No Synthase ◽  
Mesenteric Arteries ◽  
Superoxide Anions ◽  
Nos Isoforms ◽  
Nos Gene

We have previously demonstrated that endothelium-derived hydrogen peroxide (H 2 O 2 ) is an endothelium-derived hyperpolarizing factor (EDHF) in mouse and human mesenteric arteries and porcine coronary microvessels. We also have demonstrated that endothelial NO synthase (eNOS) is a major source of EDHF/H 2 O 2 , where Cu,Zn-superoxide dismutase (SOD) plays an important role to dismutate eNOS-derived superoxide anions to EDHF/H 2 O 2 in animals and humans. However, the mechanism for the endothelial production of H 2 O 2 as an endogenous EDHF remains to be elucidated. Indeed, some EDHF-mediated responses still remain in singly eNOS −/− mice and the remaining responses are also sensitive to catalase that dismutates H 2 O 2 to form water and oxygen. It is widely known that 3 NOS isoforms (neuronal, inducible, and endothelial) compensate each other. In this study, we examined the effects of genetic disruption of all NOS isoforms (n/i/eNOS −/− ) on EDHF responses in mice. We examined the contribution of the whole NOS system to EDHF-mediated responses in eNOS −/− , n/eNOS −/− and n/i/eNOS −/− mice that we have recently generated. Isometric tensions and membrane potentials were recorded by organ chamber experiments and microelectrode technique, respectively. EDHF-mediated relaxations and hyperporalizations in response to acetylcholine of mesenteric arteries were progressively reduced as the number of disrupted NOS genes increased (n=6 each), whereas vascular smooth muscle functions were preserved (n=6 each). Expressions of endothelial NOS isoforms in the NOSs −/− mice were compensated by NOS gene that had not been disrupted (n=5 each). Laser confocal microscopic examination demonstrated that endothelial H 2 O 2 and superoxide production was absent in n/i/eNOS −/− mice (n=3–5), whereas antihypertensive treatment with hydralazine failed to improve the EDHF-mediated responses (n= 4). Involvement of NOS uncoupling was ruled out as modulation of BH 4 synthesis had no effects (n=6–7) and BH 4 /BH 2 ratio (an index of BH 4 bioavailability) was preserved (n=4). These results provide the first direct evidence that EDHF-mediated responses are totally dependent on endothelial NOSs system in mouse mesenteric arteries.

scholarly journals A Concerted Role of Na+—K+—Cl− Cotransporter and Na+/Ca2+ Exchanger in Ischemic Damage

2007 ◽  
Vol 28 (4) ◽  
pp. 737-746 ◽  
Author(s):  
Jing Luo ◽  
Yanping Wang ◽  
Hai Chen ◽  
Douglas B Kintner ◽  
Sam W Cramer ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Mortality Rate ◽  
Neuronal Death ◽  
Cortical Neurons ◽  
Infarct Volume ◽  
Glucose Deprivation ◽  
Ischemic Damage ◽  
Oxygen And Glucose Deprivation

Na+–K+–Cl− cotransporter isoform 1 (NKCC1) and Na+/Ca2+ exchanger isoform 1 (NCX1) were expressed in cortical neurons. Three hours of oxygen and glucose deprivation (OGD) significantly increased expression of full-length NCX1 protein (∼116 kDa), which remained elevated during 1 to 21 h reoxygenation (REOX) and was accompanied with concurrent cleavage of NCX1. Na+/Ca2+ exchanger isoform 1 heterozygous (NCX1+/−) neurons with ∼50% less of NCX1 protein exhibited ∼64% reduction in NCX-mediated Ca2+ influx. Expression of NCX1 and NKCC1 proteins was reduced in double heterozygous (NCX1+/−/NKCC1+/−) neurons. NCX-mediated Ca2+ influx was nearly abolished in these neurons. Three-hour OGD and 21-h REOX caused ∼80% mortality rate in NCX1+/+ neurons and in NCX1+/− neurons. In contrast, NKCC1+/− neurons exhibited ∼45% less cell death. The lowest mortality rate was found in NCX1+/−/NKCC1+/− neurons (∼65% less neuronal death). The increased tolerance to ischemic damage was also observed in NCX1+/−/NKCC1+/− brains after transient cerebral ischemia. NCX1+/−/NKCC1+/− mice had a significantly reduced infarct volume at 24 and 72 h reperfusion. In conclusion, these data suggest that NKCC1 in conjunction with NCX1 plays a role in reperfusion-induced brain injury after ischemia.

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