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 Neuroprotective Effect Of Musk On Rat Brain Ischemic Model

2020 ◽  
Author(s):  
Radnaa Gochoo ◽  
Oyuntsetseg Namsrai ◽  
Dagvatseren Begzsuren ◽  
Bat-Erdene Jargalsaikhan ◽  
Chimedragchaa Chimedtseren
Keyword(s):  
Cerebral Ischemia ◽  
Rat Brain ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Neurological Deficits ◽  
Control Group ◽  
Ischemic Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Significant Difference

Abstract Background Stroke is leading cause of morbidity and mortality in worldwide. Despite valuable progresses in understanding neurological deficits after stroke, its therapeutic options are remaining limited. We aimed to study the neuroprotective effect of musk on cerebral ischemia/reperfusion injury model rats.Methods:In our experiment, we used 180 whore meal breed Wistar rats which weigh 180-220 g and divided these rats into 50 mg/kg of musk, 100 mg/kg of musk, 10 mg/kg of nimodipine, the ischemic-reperfusion groups by filling the midriff of the brain and take the drugs for 7 days in each group. Cerebral ischemia/reperfusion was induced in rats by temporary middle cerebral artery occlusion-reperfusion (MCAO/R) followed by treatment with musk at 50 mg/kg and 100 mg/kg doses. On days 1, 3 and 7 after MCAO/R, TGF-β, BDNF, TrkB and NGF mRNA expressions in the rat brain tissue were quantitatively analyzed using RT-PCR.Results:Musk 50 and 100 mg/kg treated groups brain stroke size were significantly decreased compared with the experimental group at 1, 3 and 7 days. Moreover, brain BDNF, TrkB, NGF and TGF-β mRNA express were not significant difference between experimental and control group. Also 3rd and 7th day, the data indicate that Musk 50 and 100 mg/kg were significantly (p<0,05) effective increasing rats brain BDNF, TrkB, NGF and TGF- β mRNA express in rats with ischemic stroke induced by MCAO/R. Conclusions: The 50 and 100 mg/kg doses of musk lead to increase neuro-protective factors BDNF, TRkB, NGF and TGF- β expression of mRNA in ischemic-reperfusion rat model. It implies that the Mongolian musk supports the neurogenesis of neuronal cell.

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 Ginkgetin attenuates cerebral ischemia–reperfusion induced autophagy and cell death via modulation of the NF-κB/p53 signaling pathway

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Jianqing Pan ◽  
Xiang Li ◽  
Fei Guo ◽  
Zhigang Yang ◽  
Lingling Zhang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Cerebrovascular Accident ◽  
Ischemia Reperfusion ◽  
Nuclear Factor Κb ◽  
Neurological Deficits ◽  
Nuclear Factor ◽  
P53 Signaling ◽  
Cerebral Ischemia Reperfusion ◽  
P53 Signaling Pathway

Abstract Background: Cerebral ischemia–reperfusion (I/R) injury is the key to fatality in cerebrovascular accident, hence further endeavor is warranted to delineate the mechanism underlying its lethal aggravation procedure. In the present study, we aimed to elucidate the anti-autophagy and anti-apoptosis effects of ginkgetin via nuclear factor κB (NF-κB)/p53 pathway in cerebral I/R rats. Methods: Rats were administrated 2-h occlusion of right middle cerebral artery before the 24-h reperfusion followed. There were three doses of ginkgetin (25, 50, 100 mg/kg) given intraperitoneally (i.p.) after the 2-h ischemia, and Pifithrin-α (PFT-α, p53 inhibitor), SN50 (NF-κB inhibitor) and 3-methyladenine (3-MA, autophagy inhibitor) was administered 20 min before the ischemia, respectively. Results: The neurological deficits decreased significantly with the administration of ginkgetin. The concentrations of microtubule-associated protein 1 light chain 3-II and p53 were significantly decreased by PFT-α, 3-MA and ginkgetin. The concentrations of Beclin 1, damage-regulated autophagy modulator, cathepsin B and cathepsin D were significantly decreased due to the administration of PFT-α, ginkgetin and SN50. Furthermore, the concentrations of Bax and p53-upregulated modulator of apoptosis were significantly decreased with that of Bcl-2 being significantly increased by administration of SN50, PFT-α and ginkgetin. Conclusion: Ginkgetin can alleviate cerebral ischemia/reperfusion induced autophagy and apoptosis by inhibiting the NF-κB/p53 signaling pathway.

scholarly journals miR-380-5p facilitates NRF2 and attenuates cerebral ischemia/reperfusion injury-induced neuronal cell death by directly targeting BACH1

2021 ◽  
Vol 12 (1) ◽  
pp. 210-217
Author(s):  
Yibiao Wang ◽  
Min Xu
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Luciferase Assay ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Abstract Background This study aimed to explore the role of miR-380-5p in cerebral ischemia/reperfusion (CIR) injury-induced neuronal cell death and the potential signaling pathway involved. Methodology Human neuroblastoma cell line SH-SY5Y cells were used in this study. Oxygen and glucose deprivation/reperfusion (OGD/R) model was used to mimic ischemia/reperfusion injury. CCK-8 assay and flow cytometry were used to examine cell survival. Quantitative real time PCR (RT-qPCR) assay and Western blotting were used to measure the change of RNA and protein expression, respectively. TargetScan and Luciferase assay was used to confirm the target of miR-380-5p. Malondialdehyde (MDA) superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) were measured using commercial kits. Results miR-380-5p was downregulated in SH-SY5Y cells after OGD/R. Cell viability was increased by miR-380-5p, while cell apoptosis was reduced by miR-380-5p mimics. MDA was reduced by miR-380-5p mimics, while SOD and GSHPx were increased by miR-380-5p. Results of TargetScan and luciferase assay have showed that BACH1 is the direct target of miR-380-5p. Expression of NRF2 was upregulated after OGD/R, but was not affected by miR-380-5p. mRNA expression of HO-1 and NQO1 and ARE activity were increased by miR-380-5p. Overexpression of BACH1 reversed the antioxidant and neuroprotective effects of miR-380-5p. Conclusion miR-380-5p inhibited cell death induced by CIR injury through target BACH1 which also facilitated the activation of NRF2, indicating the antioxidant and neuroprotective effects of miR-380-5p.

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