scholarly journals Exogenous hydrogen sulfide attenuates cerebral ischemia–reperfusion injury by inhibiting autophagy in mice

2016 ◽  
Vol 94 (11) ◽  
pp. 1187-1192 ◽  
Author(s):  
Mengyang Shui ◽  
Xiaoyan Liu ◽  
Yuanjun Zhu ◽  
Yinye Wang
Keyword(s):  
Hydrogen Sulfide ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Western Blot Assay

Hydrogen sulfide (H2S), the third gas transmitter, has been proven to be neuroprotective in cerebral ischemic injury, but whether its effect is mediated by regulating autophagy is not yet clear. The present study was undertaken to explore the underlying mechanisms of exogenous H2S on autophagy regulation in cerebral ischemia. The effects and its connection with autophagy of NaHS, a H2S donor, were observed through neurological deficits and cerebral infarct volume in middle cerebral artery occlusion (MCAO) mice; autophagy-related proteins and autophagy complex levels in the ischemic hemisphere were detected with Western blot assay. Compared with the model group, NaHS significantly decreased infarct volume and improved neurological deficits; rapamycin, an autophagy activator, abolished the effect of NaHS; NaHS decreased the expression of LC3-II and up-regulated p62 expression in the ischemic cortex 24 h after ischemia. However, NaHS did not significantly influence Beclin-1 expression. H2S has a neuroprotective effect on ischemic injury in MCAO mice; this effect is associated with its influence in down-regulating autophagosome accumulation.

RTN1-C mediates cerebral ischemia/reperfusion injury via modulating autophagy

2020 ◽  
Author(s):  
Jun Ling ◽  
Haijian Cai ◽  
Muya Lin ◽  
Shunli Qi ◽  
Jian Du ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Cerebral Ischemia Reperfusion

Abstract It has been widely accepted that autophagic cell death exacerbates the progression of cerebral ischemia/reperfusion (I/R). Our previous study revealed that overexpression of reticulon protein 1-C (RTN1-C) is involved in cerebral I/R injury. However, the underlying mechanisms have not been studied intensively. This study was designed to evaluate the effect of RTN1-C on autophagy under cerebral I/R. Using an in vitro oxygen-glucose deprivation followed by reoxygenation and a transient middle cerebral artery occlusion model in rats, we found that the expression of RTN1-C protein was significantly upregulated. We also revealed that RTN1-C knockdown suppressed overactivated autophagy both in vivo and in vitro, as indicated by decreased expressions of autophagic proteins. The number of Beclin-1/propidium iodide-positive cells was significantly less in the LV-shRTN1-C group than in the LV-shNC group. In addition, rapamycin, an activator of autophagy, aggravated cerebral I/R injury. RTN1-C knockdown reduced brain infarct volume, improved neurological deficits, and attenuated cell vulnerability to cerebral I/R injury after rapamycin treatment. Taken together, our findings demonstrated that the modulation of autophagy from RTN1-C may play vital roles in cerebral I/R injury, providing a potential therapeutic treatment for ischemic brain injury.

scholarly journals The Antiapoptosis Effect of Geum japonicum Thunb. var. chinense Extracts on Cerebral Ischemia Reperfusion Injury via PI3K/Akt Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Bingjin Ou ◽  
Wei Tao ◽  
Songbai Yang ◽  
Jiateng Feng ◽  
Jinfeng Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Activity Level ◽  
Neurological Deficits ◽  
High Dose ◽  
Dependent Manner ◽  
Cerebral Ischemia Reperfusion

Geum japonicum Thunb. var. chinense (GJ) is a type of wild vegetable found in China and other Asian countries; it has been reported that its extracts possess a neuroprotective effect against cerebral ischemia reperfusion (CIR) injury. The aim of this study is to explore the effect GJ extracts on transient focal CIR injury and neurons apoptosis and to clarify its possible underlying mechanisms in vivo. Our results indicated that pretreatment with GJ extracts significantly ameliorated the infarct volume, decreased neurological deficits, lessened neural cells apoptosis, downregulated GFAP activity level, and increased surviving neurons. Moreover, GJ extracts preadministration increased Bcl-2 levels and attenuated the increase in the expressions of Bax and it also lowered the cleaved caspase-3 activity in ischemic cortex tissues which was caused by CIR and increased the expression of PI3K and p-Akt. The above effects of high dose of GJ (GJ-H) group were much better than those of low dose of GJ (GJ-L), which indicated that GJ extracts may be helpful in the suppression of CIR injury with a dose-dependent manner.

scholarly journals A20-Binding Inhibitor of NF-κB 1 Ameliorates Neuroinflammation and Mediates Antineuroinflammatory Effect of Electroacupuncture in Cerebral Ischemia/Reperfusion Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xueling Zhou ◽  
Wenhao Lu ◽  
You Wang ◽  
Jiani Li ◽  
Yong Luo
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Cerebral Ischemia Reperfusion ◽  
Neuroprotective Strategy

A20-binding inhibitor of NF-κB 1 (ABIN1) is an inhibitor of NF-κB and exerts anti-inflammatory effect. Electroacupuncture (EA) is considered as a neuroprotective strategy by inhibiting neuroinflammatory damage after cerebral ischemia. This study was performed to explore the role of ABIN1 and investigate whether the ABIN1 is involved in the mechanism of EA in cerebral ischemia/reperfusion (I/R) rats. Male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and received EA after reperfusion once a day. Lentivirus-mediated ABIN1 gene knockdown was used to detect the role of ABIN1 in neuroinflammation after I/R. ABIN1 expression, proinflammatory cytokine levels, microglial activation, neurological function, infarct volumes, and NF-κB activation were assessed. ABIN1 expression was elevated in the peri-infarct cortex and was further upregulated by EA. ABIN1 knockdown increased the levels of proinflammatory cytokines and activation of microglia, worsened neurological deficits, and enlarged the infarct volume. Moreover, ABIN1 was blocked to partially reverse the neuroprotective effect of EA, and this treatment weakened the ability of EA to suppress NF-κB activity. Based on these findings, ABIN1 is a potential suppressor of neuroinflammation and ABIN1 mediates the antineuroinflammatory effect of EA in cerebral I/R rats.

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

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.

scholarly journals Neuroprotective and Anti-Inflammatory Effect of Pterostilbene Against Cerebral Ischemia/Reperfusion Injury via Suppression of COX-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjun Yan ◽  
Dongqing Ren ◽  
Xiaoxue Feng ◽  
Jinwen Huang ◽  
Dabin Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Polymorphonuclear Leucocyte ◽  
The Body ◽  
Cox 2 ◽  
Anti Inflammatory

Background: The incidence of cerebral ischemia disease leading cause of death in human population worldwide. Treatment of cerebral ischemia remains a clinical challenge for researchers and mechanisms of cerebral ischemia remain unknown. During the cerebral ischemia, inflammatory reaction and oxidative stress plays an important role. The current investigation scrutinized the neuroprotective and anti-inflammatory role of pterostilbene against cerebral ischemia in middle cerebral artery occlusion (MCAO) rodent model and explore the underlying mechanism.Methods: The rats were divided into following groups viz., normal, sham, MCAO and MCAO + pterostilbene (25 mg/kg) group, respectively. The groups received the oral administration of pterostilbene for 30 days followed by MCAO induction. The neurological score, brain water content, infarct volume and Evan blue leakage were estimated. Hepatic, renal, heart, inflammatory cytokines and inflammatory mediators were estimated.Results: Pterostilbene treatment significantly (p < 0.001) improved the body weight and suppressed the glucose level and brain weight. Pterostilbene significantly (p < 0.001) reduced the hepatic, renal and heart parameters. Pterostilbene significantly (p < 0.001) decreased the level of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and decreased the level of malonaldehyde (MDA), 8-Hydroxy-2′-deoxyguanosine (8-OHdG). Pterostilbene significantly (p < 0.001) inflammatory cytokines and inflammatory parameters such as cyclooxygenase-2 (COX-2), inducible nitric oxidase synthase (iNOS) and prostaglandin (PGE2). Pterostilbene significantly (p < 0.001) down-regulated the level of metalloproteinases (MMP) such as MMP-2 and MMP-9. Pterostilbene suppressed the cellular swelling, cellular disintegration, macrophage infiltration, monocyte infiltration and polymorphonuclear leucocyte degranulation in the brain.Conclusion: In conclusion, Pterostilbene exhibited the neuroprotective effect against cerebral ischemia in rats via anti-inflammatory mechanism.

scholarly journals Deficiency of PAR4 Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

2010 ◽  
Vol 30 (5) ◽  
pp. 1044-1052 ◽  
Author(s):  
Yingying Mao ◽  
Ming Zhang ◽  
Ronald F Tuma ◽  
Satya P Kunapuli
Keyword(s):  
Cerebral Ischemia ◽  
Platelet Activation ◽  
Cerebral Edema ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Wild Type ◽  
Cerebral Ischemia Reperfusion ◽  
The Usa

Stroke is the third leading cause of death in the USA. Antithrombotic therapy targeting platelet activation is one of the treatments for ischemic stroke. Here we investigate the role of one of the thrombin receptors, protease-activated receptor 4 (PAR4), in a mouse transient middle cerebral artery occlusion (MCAO) model. After a 60 min MCAO and 23 h reperfusion, leukocyte and platelet rolling and adhesion on cerebral venules, blood–brain barrier (BBB) permeability, and cerebral edema were compared in PAR4-deficient mice and wild-type mice. Cerebral infarction volume and neuronal death were also measured. PAR4−/− mice had more than an 80% reduction of infarct volume and significantly improved neurologic and motor function compared with wild-type mice after MCAO. Furthermore, deficiency of PAR4 significantly inhibits the rolling and adhesion of both platelets and leukocytes after MCAO. BBB disruption and cerebral edema were also attenuated in PAR4−/− mice compared with wild-type animals. The results of this investigation indicate that deficiency of PAR4 protects mice from cerebral ischemia/reperfusion (I/R) injury, partially through inhibition of platelet activation and attenuation of microvascular inflammation.

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 ofPanax ginsengextract against cerebral ischemia–reperfusion-injury-induced oxidative stress in middle cerebral artery occlusion models

FACETS ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 52-68 ◽  
Author(s):  
Mufzala Shamim ◽  
Nazish Iqbal Khan
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Lipid Profile ◽  
Liver Enzymes ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Liver And Kidney ◽  
Cerebral Artery Occlusion

The present study investigated the in vivo neuroprotective role of Panax ginseng extract (PGE) pretreatment against transient cerebral ischemia in a middle cerebral artery occlusion (MCAO) model. Rats were randomly divided as follows: group I, control; group II, sham-operated; group III, where animals were subjected to MCAO surgery; and group IV, where animals were orally administered 10 mL PGE per day (200 mg/kg of body weight per day) for 30 d followed by MCAO induction at day 31. Following 24 h of reperfusion, blood and tissue (brain, liver, and kidney) samples were collected for biochemical and histopathological examination. Biochemical testing included lipid profile, liver enzymes, kidney function tests, C-reactive protein (CRP), lactate dehydrogenase (LDH), glucose, and total protein estimation. Tissue antioxidants (catalase, superoxide dismutase, and glutathione) were assessed in brain, liver, and kidney tissues. MCAO-induced histopathological changes were also examined in the tissues. Pretreatment with PGE showed significant improvement in tissue antioxidant status in brain, liver and kidney tissues. PGE treatment maintains plasma lipid profile, liver enzymes, kidney function, and CRP, LDH, and glucose levels. Histologically, monocytes and macrophage infiltration were observed in the tissues of MCAO animals, whereas PGE treatment preserved tissue architecture and minimal monocyte infiltration. PGE supplementation showed a neuroprotective effect against ischemia–reperfusion injury by effectively increasing endogenous antioxidant enzyme activity.

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

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Meng Wang ◽  
Xiaokun Geng ◽  
Chaitu Dandu ◽  
Radhika Patel ◽  
Yuchuan Ding
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Normobaric Oxygen ◽  
Sequestosome 1 ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

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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