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 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.

PKM2 Aggravates Cerebral Ischemia Reperfusion-Induced Neuroinflammation via TLR4/MyD88/TRAF6 Signaling Pathway

2021 ◽  
pp. 1-9
Author(s):  
Baocheng Zhang ◽  
Jie Shen ◽  
Zhiyue Zhong ◽  
Lin Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Western Blot ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Neurological Dysfunction ◽  
Cell Counting ◽  
Neurological Deficits ◽  
Tetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion

Objectives: Cerebral ischemia-reperfusion (I/R) injury is the leading cause of ischemic stroke. Pyruvate Kinase isozymes M2 (PKM2), as a critical glycolytic enzyme during glycolysis, is involved in neuronal apoptosis in rats with hypoxic-ischemic encephalopathy. This study focused on functional investigation and potential molecular mechanism toward PKM2 in cerebral I/R injury. Methods: Cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in vivo or oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro. qRT-PCR and Western blot were used to detect the expression of PKM2 in I/R injury models. The effects of PKM2 on I/R injury were determined via triphenyl tetrazolium chloride staining and evaluation of neurological deficits. Cell Counting Kit-8 was employed to detect cell viability, and ELISA was conducted to detect pro-inflammatory cytokines. The underlying mechanism involved in regulation of PKM2 on I/R injury was investigated via ELISA and Western blot. Results: PKM2 was upregulated after cerebral I/R injury. Knockdown of PKM2 alleviated MCAO-induced infarction and neurological dysfunction. Moreover, PKM2 knockdown also alleviated OGD/R-induced neuronal cell injury and inflammatory response. Mechanistically, PKM2 knockdown-induced neuroprotection was accompanied by inhibition of high-mobility group box 1 (HMGB1), reflected by inactivation of TLR4/MyD88 (myeloid differentiation factor 88)/TRAF6 (TNF receptor-associated factor 6) signaling pathway. Conclusions: Knockdown of PKM2 attenuated cerebral I/R injury through HMGB1-mediated TLR4/MyD88/TRAF6 expression change, providing a potential target for cerebral I/R injury treatment.

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 &lt; 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 &lt; 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 &lt; 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 The Mechanism of Ischemic Preconditioning Up-Regulation the Expression of Tissue Kallikrein Protects Neurons from Cerebral Ischemia/Reperfusion Injury

2020 ◽  
Author(s):  
Lu Su ◽  
Dan Liang ◽  
Shenyi Kuang ◽  
Qiang Dong ◽  
Xiang Han ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cytochrome C ◽  
Western Blot ◽  
Ischemic Preconditioning ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Cresyl Violet ◽  
Tissue Kallikrein ◽  
Cerebral Ischemia Reperfusion

Abstract Ischemic stroke is an important clinical problem with few effective treatments. Many studies have shown that exogenous tissue kallikrein (TK) can protect neurons against hypoxia/reoxygenation injury. In the present study, we explored the possible molecular mechanisms underlying the regulation and function of endogenous TK. Western blot, chromatin immunoprecipitation (ChIP) and real-time PCR (RT-PCR) revealed that cerebral ischemic preconditioning (IP) upregulated the expression of endogenous TK by regulating the acetylation of histone H3. Cresyl violet staining was used to assess the neuroprotective role of endogenous TK on rat hippocampal CA1 neurons against cerebral ischemia/reperfusion (I/R) injury. Western blot results showed that IP activated the expression of p-Raf, p-MEK1/2 and p-ERK1/2 by Western blot. Moreover, Western blotfurther determined that endogenous TK upregulated the expression of p-Bad, depressed the release of cytochrome c and Bax from mitochondria to the cytosol and inhibited caspase-3 activation. In conclusion, endogenous TK can play a neuroprotective role and its upregulation induced by IP treatment can activate the phosphorylation of Raf, MEK1/2 and p-ERK1/2, depress the release of cytochrome c and Bax from mitochondria to the cytosol and inhibit caspase-3 activation.

scholarly journals Protective Effect of Low-Dose Alcohol Consumption against Post-Ischemic Neuronal Apoptosis: Role of L-PGDS

2021 ◽  
Vol 23 (1) ◽  
pp. 133
Author(s):  
Chun Li ◽  
Jiyu Li ◽  
Ethyn G. Loreno ◽  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Alcohol Consumption ◽  
Protective Effect ◽  
Neuronal Apoptosis ◽  
Low Dose ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Prostaglandin D2 ◽  
Permanent Disability ◽  
Cerebral Ischemia Reperfusion

Ischemic stroke is one of the leading causes of permanent disability and death in adults worldwide. Apoptosis is a major element contributing to post-ischemic neuronal death. We previously found that low-dose alcohol consumption (LAC) protects against neuronal apoptosis in the peri-infarct cortex following transient focal cerebral ischemia. Lipocalin-type prostaglandin D2 synthase (L-PGDS), which is mainly localized in the central nervous system (CNS), was previously shown to inhibit neuronal apoptosis. Therefore, we determined whether L-PGDS is involved in the protective effect of LAC against post-ischemic neuronal apoptosis. Wild-type (WT), CaMKIIαCreERT2/+/L-PGDS+/+, and CaMKIIαCreERT2/+/L-PGDSflox/flox mice on a C57BL/6J background were gavage fed with ethanol or volume-matched water once a day for 8 weeks. Tamoxifen (2 mg/day) was given intraperitoneally to CaMKIIαCreERT2/+/L-PGDS+/+ and CaMKIIαCreERT2/+/L-PGDSflox/flox mice for 5 days during the fourth week. AT-56 (30 mg/kg/day), a selective inhibitor of L-PGDS, was given orally to AT-56-treated WT mice from the fifth week for four weeks. Cerebral ischemia/reperfusion (I/R) injury, TUNEL-positive neurons, and cleaved caspase-3-positive neurons were measured at 24 h of reperfusion after a 90 min unilateral middle cerebral artery occlusion (MCAO). We found that 0.7 g/kg/day but not 2.8 g/kg/day ethanol significantly upregulated L-PGDS in the cerebral cortex. In addition, 0.7 g/kg/day ethanol diminished cerebral ischemia/reperfusion (I/R) injury and TUNEL-positive and cleaved caspase-3-positive neurons in the peri-infarct cortex in WT and CaMKIIαCreERT2/+/L-PGDS+/+ mice. Furthermore, the neuroprotective effect of 0.7 g/kg/day ethanol was alleviated in AT-56-treated WT and CaMKIIαCreERT2/+/L-PGDSflox/flox mice. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing post-ischemic neuronal apoptosis via an upregulated L-PGDS.

scholarly journals Effects of Permissive Hypercapnia on Transient Global Cerebral Ischemia–Reperfusion Injury in Rats

2010 ◽  
Vol 112 (2) ◽  
pp. 288-297 ◽  
Author(s):  
Qiang Zhou ◽  
Bo Cao ◽  
Li Niu ◽  
Xiaoguang Cui ◽  
Hongwei Yu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurologic Deficit ◽  
Aquaporin 4 ◽  
Global Cerebral Ischemia ◽  
Ultrastructural Changes ◽  
Permissive Hypercapnia ◽  
Group I

Background Permissive hypercapnia is a widely practiced protective ventilatory strategy that has significant protective effects on several models of in vitro and in vivo neuronal injury. However, conclusive effects of permissive hypercapnia on cerebral ischemia are still unknown. Methods One hundred sixty male Wistar rats were divided into five groups: S group (control), ischemia-reperfusion (I/R) group, P1 group, P2 group, and P3 group. I/R was induced by bilateral occlusion of the common carotid arteries, combined with controlled hypotension for 15 min. In groups P1, P2, and P3, the rats inhaled carbon dioxide for 2 h during reperfusion to keep Paco2 within the ranges of 60-80 mmHg, 80-100 mmHg, and 100-120 mmHg, respectively. After 24 and 72 h, neurologic deficit scores, ultrastructural changes, apoptotic neurons, and brain wet-to-dry weight ratios were observed. Caspase-3 and aquaporin-4 protein expression and caspase-3 activity were analyzed. Results Compared with groups I/R and P3, groups P1 and P2 had better neurologic deficit scores and fewer ultrastructural histopathologic changes. I/R-induced cerebral apoptosis was also significantly reduced. The neuroprotective effect was significantly increased in the P2 group compared with the P1 group. There was a significant increase of brain water content and of aquaporin-4 levels in the P3 group. Conclusions Mild to moderate hypercapnia (Paco2 60-100 mmHg) is neuroprotective after transient global cerebral I/R injury. Such a protection might be associated with apoptosis-regulating proteins. In contrast, severe hypercapnia (Paco2 100-120 mmHg) increased brain injury, which may be caused by increased brain edema.

Syringin protects against cerebral ischemia/reperfusion injury via inhibiting neuroinflammation and TLR4 signaling

Perfusion ◽  
2021 ◽  
pp. 026765912110070
Author(s):  
Yan Liu ◽  
Xuyao Zhu ◽  
Xiuxia Tong ◽  
Ziqiang Tan
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Learning And Memory ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cerebral Damage ◽  
Memory Ability ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Introduction: Cerebral ischemia/reperfusion injury (CI/R) is associated with high mortality and remains a large challenge in the clinic. Syringin is a bioactive compound with anti-inflammation, antioxidant, as well as neuroprotective effects. Nevertheless, whether syringin could protect against CI/R injury and its potential mechanism was still unclear. Methods: Rats were randomly divided into five groups: sham group, syringin group, CI/R group, CI/R + syringin group, and CI/R + syringin + LPS (TLR4 agonist) group. The CI/R injury rat model was established by the middle cerebral artery occlusion (MCAO). The learning and memory ability of rats was estimated by the Morris water maze test. Modified neurological severity score test (mNSS) and infarct volume were detected to assess the neuroprotective effect of syringin. ELISA and RT-qPCR were used to analyze the concentration of proinflammation cytokines and the expression of TLR4. Results: CI/R injury induced increased mNSS scores and decreased learning and memory ability of rats. Syringin could significantly protect against CI/R injury as it decreased the cerebral damage and improved the cognitive ability of CI/R rats. Moreover, syringin also reduced neuroinflammation of CI/R injury rats. Additionally, TLR4 was significantly upregulated in CI/R injury rats, which was suppressed by syringin. The activation of TLR4 reversed the neuroprotective effect of syringin in CI/R rats. Conclusion: Syringin decreased the inflammation reaction and cerebral damage in CI/R injury rats. The neuroprotective effect of syringin may be correlated with the inhibition of TLR4.

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