scholarly journals YiQiFuMai Powder Injection Ameliorates Cerebral Ischemia by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Guosheng Cao ◽  
Huana Zhou ◽  
Nan Jiang ◽  
Yuwei Han ◽  
Yang Hu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Er Stress ◽  
Signaling Pathways ◽  
Pc12 Cells ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Neurological Deficits ◽  
Powder Injection

YiQiFuMai (YQFM) powder injection as a modern preparation derived from Sheng Mai San, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, its neuroprotective effect and underlying mechanism in cerebral ischemia remain to be explored. The present study was designed to investigate the neuroprotective effect of YQFM on endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in the permanent middle cerebral artery occlusion- (MCAO-) injured mice and the oxygen-glucose deprivation- (OGD-) induced pheochromocytoma (PC12) cells. The results showed that single administration of YQFM (1.342 g/kg, i.p.) could reduce the brain infarction and improve the neurological deficits and the cerebral blood flow (CBF) after MCAO for 24 h in mice. Moreover, incubation with YQFM (100, 200, and 400 μg/mL) could increase the cell viability, decrease the caspase-3 activity, and inhibit the cell apoptosis in OGD-induced PC12 cells for 12 h. In addition, YQFM treatment could significantly modulate cleaved caspase-3 and Bcl-2 expressions and inhibit the expressions of ER stress-related marker proteins and signaling pathwaysin vivoandin vitro. In conclusion, our findings provide the first evidence that YQFM ameliorates cerebral ischemic injury linked with modulating ER stress-related signaling pathways, which provided some new insights for its prevention and treatment of cerebral ischemia diseases.

scholarly journals Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Hao Liu ◽  
Zhongren Sun ◽  
Beng Zhang ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Er Stress ◽  
Acupuncture Treatment ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Neurological Score

Abstract Background: Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia-reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. Methods: Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), Hegu (L14), and Taichong (Liv3) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. Results: Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. Conclusions: Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

scholarly journals Neuroprotective Effect of Sodium Butyrate against Cerebral Ischemia/Reperfusion Injury in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Sun ◽  
Fangyan Wang ◽  
Haixiao Li ◽  
Huiqing Zhang ◽  
Jiangtao Jin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Sodium Butyrate ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Morphological Examination ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Sodium butyrate (NaB) is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R) injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg) was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO) mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt), and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1β, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.

scholarly journals Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Lina Zhao ◽  
Huanming Li ◽  
Qian Gao ◽  
Jin Xu ◽  
Yongjie Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Ischemic Penumbra ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Berberine (BBR) has a neuroprotective effect against ischemic stroke, but its specific protective mechanism has not been clearly elaborated. This study explored the effect of BBR on the canopy FGF signaling regulator 2 (CNPY2) signaling pathway in the ischemic penumbra of rats. The model of cerebral ischemia-reperfusion injury (CIRI) was established by the thread embolization method, and BBR was gastrically perfused for 48 h or 24 h before operation and 6 h after operation. The rats were randomly divided into four groups: the Sham group, BBR group, CIRI group, and CIRI + BBR group. After 2 h of ischemia, followed by 24 h of reperfusion, we confirmed the neurologic dysfunction and apoptosis induced by CIRI in rats (p < 0.05). In the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced apoptosis proteins (CNPY2, glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP), and Caspase-3) were significantly increased, but these levels were decreased after BBR treatment (p < 0.05). To further verify the inhibitory effect of BBR on CIRI-induced neuronal apoptosis, we added an endoplasmic reticulum-specific agonist and a PERK inhibitor to the treatment. BBR was shown to significantly inhibit the expression of apoptotic proteins induced by endoplasmic reticulum stress agonist, while the PERK inhibitor partially reversed the ability of BBR to inhibit apoptotic protein (p < 0.05). These results confirm that berberine may inhibit CIRI-induced neuronal apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting a neuroprotective effect.

scholarly journals Acupuncture Protects Against Cerebral Ischemia-Reperfusion Injury Via Suppressing Endoplasmic Reticulum Stress-Mediated Autophagy and Apoptosis

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Hao Liu ◽  
Zhongren Sun ◽  
Beng Zhang ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Er Stress ◽  
Acupuncture Treatment ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Neurological Score

Abstract Background: Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia-reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. Methods: Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), Hegu (L14), and Taichong (Liv3) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. Results: Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. Conclusions: Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

scholarly journals Acupuncture protects against cerebral ischemia–reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Xiaowei Sun ◽  
Hao Liu ◽  
Zhongren Sun ◽  
Beng Zhang ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Er Stress ◽  
Acupuncture Treatment ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Neurological Score

Abstract Background Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia–reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. Methods Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), and Qubin (GB7) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. Results Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. Conclusions Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

scholarly journals Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis

2020 ◽  
Author(s):  
Xiaowei Sun ◽  
Hao Liu ◽  
Zhongren Sun ◽  
Beng Zhang ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Er Stress ◽  
Acupuncture Treatment ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Neurological Score

Abstract Background: Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia-reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. Methods: Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), Hegu (L14), and Taichong (Liv3) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. Results: Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. Conclusions: Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

scholarly journals Neuroprotective Effect of Moxibustion on Cerebral Ischemia/Reperfusion Injury in Rats by Downregulating NR2B Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhong Di ◽  
Qin Guo ◽  
Quanai Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Western Blot ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurological Dysfunction ◽  
Moxibustion Group ◽  
Cerebral Ischemia Reperfusion ◽  
Group I

Objective. Stroke is a common and frequently occurring disease of the central nervous system, which is characterized by high mortality and a high disability rate. Moxibustion is a common method for treating stroke in traditional Chinese medicine, but its neuroprotective mechanism is unknown. N-Methyl-D-Aspartate Receptor Subunit 2B (NR2B) plays an important role in neuronal apoptosis. The objective of this study was to explore the mechanisms underlying the neuroprotective effect of moxibustion on cerebral ischemia/reperfusion (I/R) injury based on NR2B. Methods. Sprague–Dawley rats were randomly divided into 5 groups: the control group, I/R group, I/R + moxibustion group, I/R + Ro25-6981 (NR2B antagonist) group, and I/R + Ro25-6981 + moxibustion group. The cerebral ischemia/reperfusion model was induced by middle cerebral artery occlusion. Before the establishment of the model, the Ro25-6981 group received intraperitoneal injections of Ro25-6981, the moxibustion group received moxibustion, and the Ro25-6981 + moxibustion group received both interventions. The neurological dysfunction was evaluated by a neurological deficiency score (NDS). The infarct volume was examined by TTC (2,3,5-triphenyltetrazolium chloride) staining. The apoptosis rate of cerebral cells in the ischemic area was examined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining, and the expression of Bcl-2, Bax, and caspase-3 was observed by western blot. NR2B and JNK were also observed by western blot. Results. Compared with the I/R group, moxibustion significantly decreased the neurological deficiency score ( P  < 0.05) and the infarct rate ( P  < 0.01) in I/R rats which were similar to those in the Ro25-6981 group. After moxibustion treatment, there was a significant decrease in the apoptosis rate ( P  < 0.001) and the protein expression levels of Bax, caspase-3, and JNK ( P  < 0.001) and an increase in the expression of Bcl-2 ( P  < 0.01). Compared with the I/R group, moxibustion downregulated the expression of NR2B and decreased the activity of NR2B in the cerebral ischemia area ( P  < 0.001). Conclusions. Moxibustion can improve neurological dysfunction and decrease infarction area and neuronal apoptosis caused by cerebral ischemia/reperfusion in rats. Its neuroprotective mechanism may be related to downregulating the expression of NR2B.

scholarly journals γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Hui-qin Li ◽  
Sheng-nan Xia ◽  
Si-yi Xu ◽  
Pin-yi Liu ◽  
Yue Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Ischemic Stroke ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Er Stress ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neuronal Cell

Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ-glutamylcysteine (γ-GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ-GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ-GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ-GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ-GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ-GC may be a promising therapeutic agent for ischemic stroke.

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