Normobaric Oxygen (NBO) Therapy Reduces Cerebral Ischemia/Reperfusion Injury through Inhibition of Early Autophagy

Objectives. Normobaric oxygen (NBO) therapy has great clinical potential in the treatment of ischemic stroke, but its underlying mechanism is unknown. Our study aimed to investigate the role of autophagy during the application of NBO on cerebral ischemia/reperfusion injury. Methods. Male Sprague Dawley rats received 2 hours of middle cerebral artery occlusion (MCAO), followed by 2, 6, or 24 hours of reperfusion. At the beginning of reperfusion, rats were randomly given NBO (95% O2) or room air (21% O2) for 2 hours. In some animals, 3-methyladenine (3-MA, autophagy inhibitor) was administered 10 minutes before reperfusion. The severity of the ischemic injury was determined by infarct volume, neurological deficit, and apoptotic cell death. Western blotting was used to determine the protein expression of autophagy and apoptosis, while mRNA expression of apoptotic molecules was detected by real-time PCR. Results. NBO treatment after ischemia/reperfusion significantly decreased infarct volume and neurobehavioral defects. The increased expression of the autophagy markers, including microtubule-associated protein 1A light chain 3 (LC3) and Beclin 1, after ischemia/reperfusion was reversed by NBO, while promoting Sequestosome 1 (p62/SQSTM1) expression. In addition, NBO reduced cerebral apoptosis in association with alleviated BAX expression and increased BCL-2 expression. 3-MA reduced autophagy and apoptotic death but did not further improve NBO-attenuated ischemic damage. Conclusion. NBO induced remarkable neuroprotection from ischemic injury, which was correlated with blocked autophagy activity.

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Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00879-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lin Guo ◽

Zhixuan Huang ◽

Lijuan Huang ◽

Jia Liang ◽

Peng Wang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Targeted Delivery ◽

Ischemia Reperfusion Injury ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Artery Occlusion ◽

Therapeutic Drug ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

Abstract Background The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Experimental design We bioengineered neuron-targeting exosomes (Exo) conjugated to a monoclonal antibody against GAP43 (mAb GAP43) to promote the targeted delivery of quercetin (Que) to ischemic neurons with high GAP43 expression and investigated the ability of Exo to treat cerebral ischemia by scavenging reactive oxygen species (ROS). Results Our results suggested that Que loaded mAb GAP43 conjugated exosomes (Que/mAb GAP43-Exo) can specifically target damaged neurons through the interaction between Exo-delivered mAb GAP43 and GAP43 expressed in damaged neurons and improve survival of neurons by inhibiting ROS production through the activation of the Nrf2/HO-1 pathway. The brain infarct volume is smaller, and neurological recovery is more markedly improved following Que/mAb GAP43-Exo treatment than following free Que or Que-carrying exosome (Que-Exo) treatment in a rat induced by MCAO/R. Conclusions Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury.

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Protective effect of extract of the Camellia japonica L. on cerebral ischemia-reperfusion injury in rats

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20180146 ◽

2019 ◽

Vol 77 (1) ◽

pp. 39-46 ◽

Cited By ~ 5

Author(s):

Weizhuo Lu ◽

Ling Xv ◽

Jiyue Wen

Keyword(s):

Cerebral Ischemia ◽

Protective Effect ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Camellia Japonica ◽

Lactate Dehydrogenase Activity ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

ABSTRACT Objective: We investigated the protective effect of the extract of the Camellia japonica L. flower on cerebral ischemia-reperfusion injury in rats. Methods: The rat ischemia-reperfusion injury was induced by middle cerebral artery occlusion for 90 minutes and reperfusion for 48 hours. The animals received an intravenous injection once a day of 20, 40, 80 mg/kg extract of C. japonica for three consecutive days before the ischemia reperfusion. The learning and memory function, the infarct volume, serum malondialdehyde (MDA) level and lactate dehydrogenase activity, and extravasation of immunoglobulin G (IgG) into cerebral parenchyma were assessed as the cell damage index. Results: Pretreatment with extract of C. japonica markedly reduced the infarct volume, serum malondialdehyde level and lactate dehydrogenase activity, and markedly inhibited the extravasation of IgG. Moreover, pretreatment with extract of C. japonica may also inhibit the learning and memory deficits induced by an ischemia-reperfusion injury. Conclusion: It was concluded that pretreatment with extract of C. japonica has a protective effect on cerebral ischemia-reperfusion injury in rats.

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Down-Regulation of Long Non-Coding RNA AK139328 Reduces Cell Inflammation and Apoptosis in Cerebral Ischemia Reperfusion Injury

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2932 ◽

2022 ◽

Vol 12 (3) ◽

pp. 609-616

Author(s):

Xuanxuan Zhu ◽

Changzheng Wu

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ischemic Injury ◽

Inflammatory Factors ◽

Related Factors ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

Parp 1

Cerebral ischemia-reperfusion injury (CIRI) refers to the phenomenon that the ischemic injury of brain leads to the injury of brain cells, and ischemic injury is further aggravated after the recovery of blood reperfusion. In this study, we first constructed Oxygen and glucose deprivation/reoxygenation (OGD/R) injury model of PC12 cells, we found that the expression of LncRNA AK139328 in model cells was significantly increased through RT-qPCR. Subsequently, we interfered LncRNA AK139328 in model cells by plasmid transfection and found that interfering LncRNA AK139328 could significantly reduce the expression of inflammatory factors, including TNF a, IL-1β, IL-6, McP-1, and oxidative stress-related factors, including ROS, MDA, LDH, while the expressions of SOD and GSHPx were significantly increased. Flow cytometry was used to detect cell apoptosis, and apoptosisrelated proteins bcl-2, Bax, cleaved-caspase3 and cleaved PARP-1 were detected by western blot. Results show that interfering LncRNA AK139328 could reduce the apoptosis rate of OGD/R cells and the expression of Bax, cleaved caspase3 and cleaved PARP-1, while increasing the expression of bcl-2. Meanwhile, we found that after interfering LncRNA AK139328, the expressions of Nrf2, HO-1, NQO-1 and phosphorylated-P65 increased, while P65 showed no significant changes. This may be related to Nrf2/HO-1 and NF-κB signaling pathways. In a word, our study showed that interfering with LncRNA AK139328 can reduce cell inflammation and apoptosis in CIRI.

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Electroacupuncture Pretreatment Attenuates Cerebral Ischemia-Reperfusion Injury through Transient Receptor Potential Vanilloid 1-Mediated Anti-Apoptosis via Inhibiting NF-kB Signaling Pathway

10.21203/rs.3.rs-657177/v1 ◽

2021 ◽

Author(s):

Nina Yin ◽

Man Long ◽

Zhigang Wang ◽

Luyao Shao ◽

Jing Bi ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Nerve Cell ◽

Transient Receptor Potential ◽

Ischemia Reperfusion Injury ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Transient Receptor Potential Vanilloid ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

Abstract Our previous study showed that electroacupuncture (EA) pretreatment elicited protective effect on cerebral ischemia-reperfusion injury in rats, at least partly, which was associated with transient receptor potential vanilloid 1 (TRPV1)-regulated anti-oxidant stress and anti-inflammation. In this study, we further investigated the possible contribution of TRPV1-mediated anti-apoptosis in EA pretreatment-evoked neuroprotection. After EA pretreatment at Baihui (GV20), bilateral Shenshu (BL23) and Sanyinjiao (SP6) acupoints, transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 6 h in rats. Then, infarct volume, nerve cell injury, neuronal apoptosis, NF-κB signaling activation, and expression of TRPV1 were evaluated by TTC staining, hematoxylin-eosin staining, transmission electron microscopy, immunochemistry, immunofluorescence, and Western blot, respectively. The presented data showed that EA pretreatment significantly reduced infarct volume, relieved nerve cell injury, decreased the expression of pro-apoptotic proteins Bax and cleaved caspase-3, increased the level of anti-apoptotic protein Bcl-2, inhibited NF-κB (p65) transcriptional activity, and curbed TRPV1 expression in MCAO rats. By contrast, enhancement of TRPV1 expression accompanying capsaicin application, the specific TRPV1 agonists, markedly accelerated nerve cell damage, aggravated neuronal apoptosis, prompted nuclear translocation of NF-κB (p65), resulting in the reversion of EA pretreatment-evoked neuroprotective effect in MCAO rats. Thus, we conclude that EA pretreatment-induced downregulation of neuronal TRPV1 expression plays an anti-apoptosis role through inhibiting NF-κB signaling pathway, thereby protecting MCAO rats from cerebral ischemia-reperfusion injury.

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Ephedrine attenuates cerebral ischemia/reperfusion injury in rats through NF-κB signaling pathway

Human & Experimental Toxicology ◽

10.1177/0960327120975456 ◽

2020 ◽

pp. 096032712097545

Author(s):

Chanhong Shi ◽

Jianhong Li ◽

Jianwei Li

Keyword(s):

Cerebral Ischemia ◽

Protein Expression ◽

Reperfusion Injury ◽

Rat Model ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

The inflammation and immune responses are critical in ischemic stroke and contribute to aggravated brain damage. Ephedrine was reported to play an important role in the control of inflammatory responses. This study was to investigate the repairing effects and potential mechanisms of ephedrine on cerebral ischemic injury in a rat model of focal cerebral ischemia. The rat model of cerebral ischemia/reperfusion injury was established using the middle cerebral artery occlusion (MCAO) method and then rats were treated with ephedrine (5 and 10 mg/kg) for 7 days. The neurobehavioral progression was assessed using the neurological scoring method. The pathology of brain tissue was evaluated by hematoxylin and eosin (H&E) staining. The infarct volume was examined by triphenyltetrazolium chloride (TTC) staining. The apoptosis in ischemic brain tissues was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Gene quantification and protein expression were detected by real-time PCR and western blot, respectively. Ephedrine treatment significantly alleviated the cerebral ischemia/reperfusion injury, evidenced by decreased neurological deficit score, infarct volume and water content. Ephedrine also decreased autophagy and apoptosis in brain tissues. Moreover, ephedrine treatment significantly reduced inflammatory responses, associating with decreasing the protein expression of p-NF-κB. These results demonstrated neuroprotective properties of ephedrine and highlighted it as a new potential anti-inflammatory agent against injury of cerebral ischemia/reperfusion.

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