scholarly journals Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Xiao Hu ◽  
Shirong Li ◽  
Desislava Met Doycheva ◽  
Lei Huang ◽  
Cameron Lenahan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Neuronal Degeneration ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Tunel Staining ◽  
Artery Ligation ◽  
Neuroprotective Effects

Oxidative stress (OS) and neuronal apoptosis are major pathological processes after hypoxic-ischemic encephalopathy (HIE). Colony stimulating factor 1 (CSF1), binding to CSF1 receptor (CSF1R), has been shown to reduce neuronal loss after hypoxic-ischemia- (HI-) induced brain injury. In the present study, we hypothesized that CSF1 could alleviate OS-induced neuronal degeneration and apoptosis through the CSF1R/PLCG2/PKA/UCP2 signaling pathway in a rat model of HI. A total of 127 ten-day old Sprague Dawley rat pups were used. HI was induced by right common carotid artery ligation with subsequent exposure to hypoxia for 2.5 h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1 h and 24 h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1 h before HI induction. Brain infarct volume measurement, cliff avoidance test, righting reflex test, double immunofluorescence staining, western blot assessment, 8-OHdG and MitoSOX staining, Fluoro-Jade C staining, and TUNEL staining were used. Our results indicated that the expressions of endogenous CSF1, CSF1R, p-CSF1R, p-PLCG2, p-PKA, and uncoupling protein2 (UCP2) were increased after HI. CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48 h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R/PLCG2/PKA/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE.

scholarly journals Pharmacological activation of GPR55 improved cognitive impairment, neuroinflammation, oxidative stress and apoptosis induced by lipopolysaccharide in mice

2020 ◽  
Author(s):  
Xin Wang ◽  
Xiao Tong Xiang ◽  
Jie Hu ◽  
Yu Mei Wu ◽  
YueYue Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Inflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Sod Activity ◽  
Neuroprotective Effects ◽  
Impaired Performance ◽  
Pro Inflammatory Cytokines

Abstract BackgroundNeuroinflammation, oxidative stress and apoptosis are implicated in the pathogenesis of Alzheimer’s disease (AD). The purpose of the present study was to investigate the neuroprotective effects and possible mechanism of G-protein coupled receptor 55 (GPR55) agonist, O-1602, on lipopolysaccharide (LPS)-induced cognitive deficits in mice. MethodsICR mice were treated with intracerebroventricular (i.c.v.) injection of LPS. Cognitive tests were performed, including the open field, Morris water maze, novel object recognition, and passive avoidance tests. The expression of GPR55, NF-κB p65, caspase-3, Bax and Bcl-2 were examined in the hippocampus by western blotting. Pro-inflammatory cytokines and microglia were detected by ELISA kit and immunohistochemical analyses, respectively. The malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were examined by assay kits. Furthermore, TUNEL-staining was used to detect neuronal apoptosis.ResultsI.c.v. injection of LPS exhibited impaired performance in the behavior tests, which were ameliorated by O-1602 treatment(2.0 or 4.0 μg/mouse, i.c.v.). Importantly, O-1602 reversed GPR55 down-regulation, decreased the expression of NF-κB p65, and suppressed the accumulation of pro-inflammatory cytokines and microglia activation, decreased malondialdehyde (MDA) level, and increased superoxide dismutase (SOD) activity. In addition, O-1602 also significantly decreased Bax and increased Bcl-2 expression as well as decreased caspase-3 activity and TUNEL-positive cells, suppressed neuronal apoptosis in the hippocampus of LPS-treated mice.Conclusionswe conclude that O-1602 may ameliorate LPS-induced cognition deficits via inhibiting neuroinflammation, oxidative stress and apoptosis mediated by NF-κB signaling in mice.

Neuroprotective Effects of Dilong on Cerebral Infarction in Rats

2020 ◽  
Vol 10 (4) ◽  
pp. 449-454
Author(s):  
Qijun Dai ◽  
Qin Xu ◽  
Pei Xu ◽  
Hongmei Yu ◽  
Yueqin Ding
Keyword(s):  
Cerebral Infarction ◽  
Inflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Infarct Volume ◽  
Neurological Impairment ◽  
Immunohistochemical Method ◽  
Tunel Staining ◽  
Antioxidant Enzyme Activities ◽  
Neuroprotective Effects ◽  
Stress Markers

Objective: The aim of the study was to investigate the effect of Dilong on cerebral infarction (CI) in a rat model. Methods: The neurological function of rats was evaluated with the mNSS. The expression of neurotrophic factors was determined using immunohistochemical method and western blotting. Hematoxylin-eosin (H&E) staining was arranged to observe the histopathologic changes. The infarct volume of brain in rats was arranged through TTC stain. Apoptosis was investigated by terminal dUTP nick end labeling (TUNEL) staining. The expressions of oxidative stress markers and pro-inflammatory cytokines were examined using ELISA assay. Results: Rats with CI manifested neurological impairment, elevated BDNF and NGF expression, augmented infarct area, enhanced neuronal apoptosis, increased antioxidant enzyme activities, decreased malondialdehyde (MDA) content in brain tissues, and accelerated production of inflammatory cytokines. With the treatment of Dilong, the neurological impairment, neuronal apoptosis, oxidative damage and inflammatory injury were all attenuated. Conclusion: Dilong could ameliorate CI in rats by anti-oxidant and antiinflammatory effects.

scholarly journals 6′-O-Galloylpaeoniflorin Attenuates Cerebral Ischemia Reperfusion-Induced Neuroinflammation and Oxidative Stress via PI3K/Akt/Nrf2 Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhongmei Wen ◽  
Weichen Hou ◽  
Wei Wu ◽  
Yang Zhao ◽  
Xuechao Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Related Factor ◽  
Neuroprotective Effects ◽  
Phosphorylated Akt

6′-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway.

scholarly journals Dl-3-n-Butylphthalide Promotes Cardiac Function, Inhibit Oxidative Stress and Myocardial Apoptosis of Chronic Heart Failure Mice via Stimulating Nrf2/HO-1 pathway

2021 ◽  
Author(s):  
Zhongyu Wang ◽  
Yan Zhang ◽  
Chun Yang ◽  
Hongliang Yang
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Signaling Pathway ◽  
Myocardial Injury ◽  
Heart Function ◽  
Regulatory Protein ◽  
Camp Response Element Binding ◽  
Tunel Staining ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Abstract PurposeHeart failure (HF) continues to threat the human health and plagues the world, however, there are limited effective drugs for HF. We aimed to investigate the protective effect of Dl-3-n-Butylphthalide (NBP) on myocardial injury in heart failure mice, and to study regulation mechanisms with Nrf2/HO-1/Ca2+-SERCA2a axis. MethodsSixty C57BL/6J mice were grouped into five groups using a random number table: sham group (Sham), Heart Failure model group (HF), Heart Failure+ NBP group (HN), Heart Failure+NBP+Nrf2 inhibitor (HNM), Heart Failure+ NBP + calmodulin-dependent protein kinase II (CaMKⅡ) antagonist, KN93 (HNK). The HF mice was prepared using left anterior descending coronary artery ligation. As animal model preparation, the heart function was detected using echocardiography. H&E and MASSON trichrome staining were performed to identify myocardial injury; The apoptosis of myocardial was examined by TUNEL staining assay. The levels of different oxidative stress-related proteins were measured through ELISA assay ; The reactive oxygen species and Nrf2 expression in heart tissue were observed with immunofluorescence assay. The levels of SERCA2a, calmodulin, endoplasmic reticulum stress regulatory protein and Nrf2/HO-1 protein were measured using western blotting. ResultsThe results demonstrated that NBP can significantly promote heart function, relieve the injury and inhibit cell apoptosis, meanwhile, reduce ERS injury in heart failure mice through increasing SERCA2a level and reducing Ca2+ influx. Finally, NBP was demonstrated to reduce CaMKⅡphosphorylation levels and decrease cAMP-response element binding protein phosphorylation levels, which suggested that NBP could also activate Nrf2/HO-1 signaling pathway. ConclusionsThis study identified that NPBs treatment promotes the cardiomyocytes ERS and alleviates myocardial injury in heart failure mice which is related with stimulating Nrf2/HO-1 signaling pathway, regulating Ca2+-SERCA2a and reducing Ca2+ influx.

scholarly journals The Blood Component Iron Causes Neuronal Apoptosis Following Intracerebral Hemorrhage via the PERK Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Muyao Wu ◽  
Rong Gao ◽  
Baoqi Dang ◽  
Gang Chen
Keyword(s):  
Intracerebral Hemorrhage ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Tunel Staining ◽  
Blood Component ◽  
Blood Components ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Protein Levels ◽  
Neurological Score

PERK signaling pathway plays an important role in neuronal apoptosis after Intracerebral hemorrhage (ICH). ICH can cause the release of blood components into the brain. However, which component in the blood plays a major role still unclear. This study was designed to investigate the activation of the PERK pathway in different blood components after ICH and explore which components have major relationships with neuronal apoptosis. Eighty-five Sprague–Dawley rats were used to establish an ICH model. Western blot (WB) and immunofluorescence (IF) were used to evaluate the expression of the PERK pathway. TUNEL staining, FJC staining and neurological score were used to evaluate neuronal apoptosis and necrosis after ICH. The results showed that protein levels of p-PERK and p-eIF2α were upregulated following ICH with the injection of Fe3+ and Fe2+ after 48 h. Then, deferoxamine (DFX) was used to study the roles of Fe3+ in ICH through the PERK signaling pathway. The results showed that injection of DFX reversed increasing protein levels and prevented neuronal apoptosis. Thus, iron plays an important role in ICH through the PERK signaling pathway. Furthermore, the reduction of iron demonstrates neuroprotective effects in ICH. This suggests that targeting intervention of the iron and PERK pathway could be an effective treatment strategy to improve ICH prognosis.

Protective role of protocatechuic acid in sevoflurane-induced neuron apoptosis, inflammation and oxidative stress in mice

2020 ◽  
Vol 38 (4) ◽  
pp. 323-331
Author(s):  
Yuhua Gao ◽  
Liping Ma ◽  
Tao Han ◽  
Meng Wang ◽  
Dongmei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Protocatechuic Acid ◽  
Protective Role ◽  
Continuous Treatment ◽  
Tunel Staining ◽  
Neuroprotective Effects ◽  
Tnf Α ◽  
Pre Treatment ◽  
And Oxidative Stress

Background: In neonatal mice, sevoflurane, inspired through the nasal cavity to act as anesthesia, triggers neuronal apoptosis, inflammation and oxidative injury that can hamper cognitive functions in the growth of the central nervous system in the later stages of life. Objective: Our study aimed to explore the potential neuroprotective effects of protocatechuic acid (PCA) to ameliorate neonatal sevoflurane-induced neurotoxicity. Methods: Male mice were pretreated with PCA (10 or 20 mg/kg) for half an hour before continuous treatment for 6 h with 3 % sevoflurane. TUNEL staining was performed to examine the apoptotic cells to record their count. ELISA was performed to evaluate the expressions of the proteins - IL-1β, IL-18 and TNF-α. Analysis of the Western blot and test of the Morris maze was determined and the results analyzed. Results: TUNEL findings assay showed a significant reduction with sevoflurane in neuronal apoptosis treated with PCA at 20 mg/kg. The expression of protein Caspase-3 showed significant changes in the group SEV + PCA (20 mg/kg). ELISA analysis showed that the levels of IL-18 and TNF-α were significantly reduced in the SEV + PCA (20 mg/kg) group as compared to SEV + PCA (10 mg/kg) group. MDA, ROS and SOD levels were noted to decrease significantly only in the SEV + PCA group (20 mg/kg) while IL-1β levels decreased in both SEV + PCA groups (10 or 20 mg/kg) respectively. Conclusions: Our findings imply that apoptosis, inflammation, and oxidative stress in the hippocampal region of neonatal mouse brain were significantly reduced by pre-treatment with PCA before sevoflurane exposure. Therefore, suggesting a role for PCA as a novel therapeutic agent in the treatment of sevoflurane anesthesia-induced neurobehavioral dysfunction.

scholarly journals Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury

2019 ◽  
Vol 20 (3) ◽  
pp. 502 ◽  
Author(s):  
Buyandelger Batsaikhan ◽  
Jing-Ya Wang ◽  
Michael Scerba ◽  
David Tweedie ◽  
Nigel Greig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Neuronal Degeneration ◽  
Neurological Deficits ◽  
Post Injury ◽  
Neuroprotective Effects ◽  
Tnf Α

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-α (TNF-α) is known to contribute to these processes. We have previously shown that 3,6′-dithiothalidomide (3,6′-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF-α in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6′-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6′-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6′-DT. Notably, neuronal oxidative stress was also suppressed by 3,6′-DT. We conclude that 3,6′-DT may represent a potential therapy to ameliorate TBI-induced functional deficits.

scholarly journals Calycosin-7-O-β-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Xiangli Yan ◽  
Aiming Yu ◽  
Haozhen Zheng ◽  
Shengxin Wang ◽  
Yingying He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Pathological Process ◽  
Neuroprotective Effects ◽  
Ht22 Cells ◽  
Positive Effects ◽  
Antioxidant Stress

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

scholarly journals Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4138
Author(s):  
Yeon-Jin Cho ◽  
Sun-Hye Choi ◽  
Ra-Mi Lee ◽  
Han-Sung Cho ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Akt Signaling ◽  
Atp Depletion ◽  
Oxygen Species ◽  
Akt Signaling Pathway ◽  
Neuroprotective Effects ◽  
Lpa1 Receptor

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

Sign in / Sign up

Export Citation Format

Share Document