scholarly journals Mitochondrial Transplantation Attenuates Cerebral Ischemia-Reperfusion Injury: Possible Involvement of Mitochondrial Component Separation

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Qiang Xie ◽  
Jun Zeng ◽  
Yongtao Zheng ◽  
Tianwen Li ◽  
Junwei Ren ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Component Separation ◽  
Mitochondrial Morphology ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Cerebral Ischemia Reperfusion ◽  
Mitochondrial Transfer ◽  
Underlying Mechanisms ◽  
Intercellular Connection

Background. Mitochondrial dysfunctions play a pivotal role in cerebral ischemia-reperfusion (I/R) injury. Although mitochondrial transplantation has been recently explored for the treatment of cerebral I/R injury, the underlying mechanisms and fate of transplanted mitochondria are still poorly understood. Methods. Mitochondrial morphology and function were assessed by fluorescent staining, electron microscopy, JC-1, PCR, mitochondrial stress testing, and metabolomics. Therapeutic effects of mitochondria were evaluated by cell viability, reactive oxygen species (ROS), and apoptosis levels in a cellular hypoxia-reoxygenation model. Rat middle cerebral artery occlusion model was applied to assess the mitochondrial therapy in vivo. Transcriptomics was performed to explore the underlying mechanisms. Mitochondrial fate tracking was implemented by a variety of fluorescent labeling methods. Results. Neuro-2a (N2a) cell-derived mitochondria had higher mitochondrial membrane potential, more active oxidative respiration capacity, and less mitochondrial DNA copy number. Exogenous mitochondrial transplantation increased cellular viability in an oxygen-dependent manner, decreased ROS and apoptosis levels, improved neurobehavioral deficits, and reduced infarct size. Transcriptomic data showed that the differential gene enrichment pathways are associated with metabolism, especially lipid metabolism. Mitochondrial tracking indicated specific parts of the exogenous mitochondria fused with the mitochondria of the host cell, and others were incorporated into lysosomes. This process occurred at the beginning of internalization and its efficiency is related to intercellular connection. Conclusions. Mitochondrial transplantation may attenuate cerebral I/R injury. The mechanism may be related to mitochondrial component separation, altering cellular metabolism, reducing ROS, and apoptosis in an oxygen-dependent manner. The way of isolated mitochondrial transfer into the cell may be related to intercellular connection.

scholarly journals Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

2020 ◽  
Author(s):  
Tian Zhang ◽  
Dan Xu ◽  
Fengyang Li ◽  
Rui Liu ◽  
Kai Hou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Umbilical Vein ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Caspase 1 ◽  
Cerebral Ischemia Reperfusion

Abstract Background: Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, the efficacy of Indobufen on cerebral ischemia/reperfusion (I/R) injury and its mechanisms remain to be investigated. Methods: In this study, the efficacy of Indobufen with both pre- (5days) and post- (15days) treatment on rats suffering middle cerebral artery occlusion/reperfusion (MCAO/R, 2h of ischemia and 24h/15days of reperfusion) was investigated. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured and underwent oxygen glucose deprivation/reoxygenation (OGD/R) injury for in vitro studies. Relationship between Indobufen and pyroptosis associated NF-κB/Caspase-1/GSDMD pathway was preliminarily discussed. Results: The pharmacodynamic tests revealed that Indobufen ameliorated I/R injury by decreasing the platelet aggregation, infarct size, brain edema and neurologic impairment in rats and rescuing cell apoptosis/pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by platelet inhibition induced regulation of the NF-κB/Caspase-1/GSDMD pathway.Conclusion: Overall, these studies indicates that Indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Neuroprotection of Saponins from Rhizoma panacis majoris in Cerebral Ischemia/Reperfusion is Related to Nrf2-Mediated Antioxidant Response: Role of Nrf2 and Bcl-2 Family Expressions

2014 ◽  
Vol 998-999 ◽  
pp. 269-274
Author(s):  
Wen Yi ◽  
Meng Qiong Shi ◽  
Guang Yao Liu ◽  
Wei Deng ◽  
Hui Lin Qin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Antioxidant Response ◽  
Related Factor ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Bioactive Component ◽  
Underlying Mechanisms

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component in Rhizoma Panacis Majoris, were reported to possess protective effects on brain injury, but the underlying mechanisms remain poorly understood. This study was performed to investigate the protective effects and possible mechanism of SRPM on cerebral ischemia/reperfusion (CI/R) injury. Neuroprotective effects of SPRM in CI/R mice was evaluated by infarct size, biochemical values, Nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family expressions. In the study, we found that SRPM exerted beneficially protective effects on CI/R injury, mainly scavenging oxidative stress-triggered overgeneration and accumulation of reactive oxygen species, improving the Nrf2-mediated antioxidant response: role of Nrf2 and Bcl-2 family expressions, and alleviating CI/R injury and cerebral cell death.

scholarly journals Modulation of Preactivation of PPAR-βon Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ge Kuang ◽  
Qin He ◽  
Yunmei Zhang ◽  
Ruichun Zhuang ◽  
Anling Xiang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Hippocampal Neurons ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Global Cerebral Ischemia ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

The aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons following GCIRI. These effects were significantly improved by pretreatment with GW0742 in the dose-dependent manner. The expressions of IL-1β, IL-6, and TNF-αwere increased after GCIRI, while the increases in these proinflammatory cytokines by GCIRI were inhibited by GW0742 pretreatment. Similarly, GW0742 pretreatment also improved the GCIRI-induced decrease in the expression of IL-10, which can act as an inhibitory cytokine to reduce cerebral ischemic injury. For another, NF-κB p65 expression was significantly increased in hippocampal neurons with apparent nuclear translocation after global cerebral IRI, and these phenomena were also largely attenuated by GW0742 pretreatment. Moreover, the mRNA and protein expressions of PPAR-βwere significantly decreased in GCIRI + GW0742 groups when compared with those in GCIRI group. Our data suggests that the PPAR-βagonist GW0742 can exert significant neuroprotective effect against GCIRI in rats via PPAR-βactivation and its anti-inflammation effect mediated by the inhibition of expression and activation of NF-κB in the hippocampus.

The protective effect of ligustrazine on rats with cerebral ischemia–reperfusion injury via activating PI3K/Akt pathway

2019 ◽  
Vol 38 (10) ◽  
pp. 1168-1177 ◽  
Author(s):  
Y Ding ◽  
J Du ◽  
F Cui ◽  
L Chen ◽  
K Li
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Ischemia Reperfusion ◽  
Pi3k Inhibitor ◽  
Akt Pathway ◽  
Control Group ◽  
Dependent Manner ◽  
Cerebral Ischemia Reperfusion ◽  
Dose Dependent

The study was to investigate the effects of ligustrazine on rats with cerebral ischemia–reperfusion (I/R) injury and to explore the potential mechanism. Transient focal cerebral ischemia Wistar rat model was established through middle cerebral artery occlusion. The cerebral I/R injury rats were treated with intraperitoneal injection of ligustrazine (1, 3, and 10 mg/kg). Human amniotic epithelial cells (HAECs) were treated with ligustrazine (1, 10, 100 μM) and PI3K inhibitor wortmannin (100 μM), following oxygen–glucose deprivation (OGD) treatment. The expression levels of protein kinase B (PKB or AKT), phospho-Akt (p-Akt), endothelial nitric oxide synthase (eNOS), and phosphor-eNOS (p-eNOS) in HAECs and brains of rats were measured by Western blot. The levels of nitric oxide (NO) in HAECs were measured by Griess method using NO2−/NO3− Assay Kit. Infarct volume and neurological deficits were evaluated 24 h after reperfusion. The levels of NO, p-Akt/Akt, and p-eNOS/eNOS in HAECs were significantly reduced after OGD, but ligustrazine treatment increased the levels of those factors in a dose-dependent manner, while those increases were reversed by PI3K inhibitor wortmannin. Similarly, p-Akt/Akt and p-eNOS/eNOS in brain tissue of rats with I/R were significantly reduced compared with control group ( p < 0.05), but ligustrazine treatment increased the levels of p-Akt and p-eNOS in a dose-dependent manner ( p < 0.05), while those increases were also reversed by using wortmannin. Ligustrazine also improved the damage of rat brain tissue caused by I/R, but wortmannin reversed the improvement. Ligustrazine plays a neuroprotective role in rats with cerebral I/R injury through the activation of PI3K/Akt pathway.

scholarly journals Total Saponins of Panax Notoginseng Exhibit Neuroprotection by The Activation of Akt/mTOR Pathway in Vitro and in Vivo

2020 ◽  
Author(s):  
Dong-Ping Wu ◽  
Yu-Wei Pan ◽  
Hua-Feng Liang ◽  
Gen-Yun Tang ◽  
Ming Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Panax Notoginseng ◽  
Mtor Pathway ◽  
Dead Cell ◽  
Cerebral Ischemia Reperfusion ◽  
Underlying Mechanisms

Abstract Background: Panax notoginseng (Burkill) F.H.Chen is a traditional Chinese medicine. The present study reports the potential therapeutic effect of total saponins of Panax notoginseng (Burkill) F.H.Chen (TSPN) on ischemic stroke and investigates the underlying mechanisms. To reveal the neuroprotective effect of TSPN on cerebral ischemia-reperfusion injury and the underlying mechanisms.Methods: Oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons was used as a model of neuronal injury. The neuroprotective effect of TSPN was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and Live/Dead cell assay. The morphology of dendrites was detected by immunofluorescence. Rat middle cerebral artery occlusion (MCAO) was used as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological score, tail hang test, TTC staining, and Nissl staining. Western blot analysis, immunohistochemistry or immunofluorescence was used to measure the changes in Akt/mTOR signaling pathway.Results: MTT showed that TSPN had a rescue effect on cortical neurons after OGD/R-treated. Flow cytometry and Live/Dead cell assay indicated that TSPN decreased neuronal apoptosis, and immunofluorescence showed that TSPN restored dendrite morphology of the damaged neurons. Moreover, TSPN down-regulated the expressions of cleaved-Caspase-3 and LC3B-II/LC3B-I, whereas up-regulated the levels of phosphorylated (p)- Akt and p-mTOR. In MCAO model, TSPN rescued defective neurological behavior and reduced infarct volume. Moreover, the expressions of Beclin-1 and LC3B in cerebral ischemic penumbra were down-regulated after the treatment of TSPN, whereas p-mTOR level was up-regulated.Conclusion: TSPN show neuroprotective effects against OGD/R-induced cortical neuronal damage and exhibit potential therapeutic effects on cerebral ischemia in rat MCAO model. Up-regulation of mTOR pathway and inhibition of the autophagic pathway could be the mechanisms that underlie the action of TSPN.

scholarly journals Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

2020 ◽  
Author(s):  
Tian Zhang ◽  
Dan Xu ◽  
Fengyang Li ◽  
Rui Liu ◽  
Kai Hou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Umbilical Vein ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Caspase 1 ◽  
Cerebral Ischemia Reperfusion

Abstract Background: Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, the efficacy of Indobufen on cerebral ischemia/reperfusion (I/R) injury and its mechanisms remain to be investigated. Methods: In this study, the efficacy of Indobufen with both pre- and post-treatment on rats suffering middle cerebral artery occlusion/reperfusion (MCAO/R) was investigated. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured and underwent oxygen glucose deprivation/reoxygenation (OGD/R) injury for in vitro studies. Relationship between Indobufen and pyroptosis associated NF-κB/Caspase-1/GSDMD pathway was preliminarily discussed. Results: The pharmacodynamic tests revealed that Indobufen ameliorated I/R injury by decreasing the platelet aggregation, infarct size, brain edema and neurologic impairment in rats and rescuing cell apoptosis/pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Conclusion: Overall, these studies indicates that Indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Sign in / Sign up

Export Citation Format

Share Document