scholarly journals Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

2021 ◽  
Author(s):  
Ya-Juan Chen ◽  
Chen Chen ◽  
Meng-Yuan Li ◽  
Qing-Qing Li ◽  
Xiu-Juan Zhang ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Flavonoid Glycoside ◽  
Western Blot Assay ◽  
Assay Result ◽  
Dependent Protein ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Ischemic

AbstractFlavonoid glycoside scutellarin (SCU) has been widely applied in the treatment of cerebral ischemic diseases in China. In this article, we conducted research on the working mechanisms of SCU in hypoxia reoxygenation (HR) injury of isolated cerebral basilar artery (BA) and erebral ischemia reperfusion (CIR) injury in rat models. In isolated rat BA rings, HR causes endothelial dysfunction (ED) and acetylcholine (ACh) induces endothelium-dependent vasodilation. The myography result showed that SCU (100 µM) was able to significantly improve the endothelium-dependent vasodilation induced by Ach. However, SCU did not affect the ACh-induced relaxation in normal BA. Further studies suggested that SCU (10–1000 µM) dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase (PKG) inhibitor Rp-8-Br-cGMPs (PKGI-rp, 4 µM). Pre-incubation with SCU (500 µM) reversed the impairment of endothelium-dependent vasodilation induced by HR, but the reversing effect was blocked if PKGI-rp (4 µM) was added. The brain slice staining test in rats’ model of middle cerebral artery occlusion (MCAO) induced CIR proved that the administration of SCU (45, 90 mg/kg, iv) significantly reduced the area of cerebral infarction. The Western blot assay result showed that SCU (45 mg/kg, iv) increased brain PKG activity and PKG protein level after CIR surgery. In conclusion, our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal. Graphic Abstract

scholarly journals Stargazin Interaction With Serine Racemase Mediates Cerebral Ischemia/Reperfusion Injury in Rats

2021 ◽  
Author(s):  
Xiaqing Yuan ◽  
Shanshan Diao ◽  
Shujun Chen ◽  
Jiajie Lu ◽  
Haitao Shen ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Serine Racemase ◽  
Dependent Protein ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Damage ◽  
Cerebral Artery Occlusion

Abstract D-Serine is thought to be involved in N-methyl-D-aspartate (NMDA)-type glutamate receptor-mediated neurotoxicity and plays a pathophysiologic role in stroke. D-Serine is synthesized by serine racemase (SR), which directly converts L-serine into D-serine. The deletion of SR has been reported to protect against cerebral ischemia damage. Additionally, SR catalytic activity is physiologically regulated by its binding to stargazin. However, whether the stargazin-SR interaction affects the level of stroke damage remains elusive. We showed that cerebral ischemia increased the interaction of stargazin and SR and decreased the levels of D-serine. Disrupting the stargazin-SR interaction by knocking down stargazin aggravated cerebral ischemic insults. We found that cerebral ischemia decreased the phosphorylation of stargazin at the Thr-321 residue, which was phosphorylated by cAMP-dependent protein kinase A (PKA). Treatment with the PKA inhibitor H89 blocked stargazin T321 phosphorylation, augmented the stargazin-SR interaction, decreased D-serine levels, and alleviated focal cerebral ischemic damage in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). Thus, the stargazin-SR interaction is a promising strategy in the treatment of stroke.

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 Isorhynchophylline Ameliorates Cerebral Ischemia/Reperfusion Injury by Inhibiting CX3CR1-Mediated Microglial Activation and Neuroinflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanyuan Deng ◽  
Ruirong Tan ◽  
Fei Li ◽  
Yuangui Liu ◽  
Jingshan Shi ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Reperfusion Therapy ◽  
Artery Occlusion ◽  
Cerebral Ischemic

Reperfusion therapy is an effective way to rescue cerebral ischemic injury, but this therapy also shows the detrimental risk of devastating disorders and death due to the possible inflammatory responses involved in the pathologies. Hence, the therapy of ischemia/reperfusion (I/R) injury is a great challenge currently. Isorhynchophylline (IRN), a tetracyclic oxindole alkaloid extracted from Uncaria rhynchophylla, has previously shown neuroprotective and anti-inflammatory effects in microglial cells. This study systematically investigates the effect of IRN on I/R injury and its underlying mechanism. The effects of IRN on neuronal injury and microglia-mediated inflammatory response were assessed on a rat model with middle cerebral artery occlusion (MCAO) and reperfusion-induced injury. We found that IRN treatment attenuated the infarct volume and improved the neurological function in I/R injury rats. IRN treatment also reduced the neuronal death rate, brain water content, and aquaporin-4 expression in the ischemic penumbra of I/R injury rats’ brains. Besides, IRN treatment could inhibit the following process, including IκB-α degradation, NF-κB p65 activation, and CX3CR1 expression, as well as the microglial activation and inflammatory response. These findings suggest that IRN is a promising candidate to treat the cerebral I/R injury via inhibiting microglia activation and neuroinflammation.

scholarly journals Neuroprotective Effect of the Ginsenoside Rg1 on Cerebral Ischemic Injury In Vivo and In Vitro Is Mediated by PPARγ-Regulated Antioxidative and Anti-Inflammatory Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yang Li ◽  
Yue Guan ◽  
Ying Wang ◽  
Chun-Lei Yu ◽  
Feng-Guo Zhai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Ginsenoside Rg1 ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Ischemic ◽  
Neuroprotective Action

The ginsenoside Rg1 exerts a neuroprotective effect during cerebral ischemia/reperfusion injury. Rg1 has been previously reported to improve PPARγexpression and signaling, consequently enhancing its regulatory processes. Due to PPARγ’s role in the suppression of oxidative stress and inflammation, Rg1’s PPARγ-normalizing capacity may play a role in the observed neuroprotective action of Rg1 during ischemic brain injury. We utilized a middle cerebral artery ischemia/reperfusion injury model in rats in addition to an oxygen glucose deprivation model in cortical neurons to elucidate the mechanisms underlying the neuroprotective effects of Rg1. We found that Rg1 significantly increased PPARγexpression and reduced multiple indicators of oxidative stress and inflammation. Ultimately, Rg1 treatment improved neurological function and diminished brain edema, indicating that Rg1 may exert its neuroprotective action on cerebral ischemia/reperfusion injury through the activation of PPARγsignaling. In addition, the present findings suggested that Rg1 was a potent PPARγagonist in that it upregulated PPARγexpression and was inhibited by GW9662, a selective PPARγantagonist. These findings expand our previous understanding of the molecular basis of the therapeutic action of Rg1 in cerebral ischemic injury, laying the ground work for expanded study and clinical optimization of the compound.

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.

scholarly journals Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Meiyao Wang ◽  
Yan Li ◽  
Renwei Zhang ◽  
Shuaimei Zhang ◽  
Hongliang Feng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Protective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Artery Occlusion

Objectives: This present study aimed to examine the effects of adiponectin-transfected endothelial progenitor cells (LV-APN-EPCs) on cerebral ischemia–reperfusion injury in rats with type 2 diabetes mellitus (T2DM) and to explore the underlying mechanisms.Methods: Seventy male Sprague–Dawley rats with T2DM were randomly divided into sham, phosphate-buffered saline (PBS), LV-APN-EPCs, LV-EPCs, and EPCs groups. Transient middle cerebral artery occlusion (MCAO) was induced by the intraluminal suture method. After 1 h of reperfusion, the five interventions were performed by tail-vein injections. The modified neurological severity score (mNSS) was used to assess neurological function before and on days 1, 7, and 14 after MCAO. After 14 days, magnetic resonance imaging scanning, hematoxylin and eosin staining, terminal dUTP nick-end labeling staining, Western blotting analysis, cluster of differentiation (CD) 31 immunofluorescence, and enzyme-linked immunosorbent assay were used to evaluate infarct rate, morphological damage, cell apoptosis, and microvessel density.Results: Compared with PBS, LV-EPCs, and EPCs groups, the LV-APN-EPCs group showed significantly lower mNSS score, lower infarct rate, and less morphological damage (all P < 0.05). In addition, compared with other groups, the LV-APN-EPCs group had significantly increased levels of B cell lymphoma/leukemia-2 (Bcl-2) protein, CD31+ microvessels, endothelial nitric oxide synthase, and vascular endothelial growth factor, and decreased levels of Bcl-2-associated X protein and neuronal apoptosis in the peri-infarct cortex (all P < 0.05).Conclusion: These results suggest that LV-APN-EPCs exert protective effects against cerebral ischemia–reperfusion injury in T2DM rats by increasing angiogenesis.

scholarly journals Oleanolic Acid Improved Inflammatory Response and Apoptosis of PC12 Cells Induced by OGD/R Through Downregulating miR-142-5P

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110180
Author(s):  
Song Gu
Keyword(s):  
Inflammatory Response ◽  
Pc12 Cells ◽  
Oleanolic Acid ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Cell Transfection ◽  
Western Blot Assay ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Related Proteins

Background Oleanolic acid (OA) has notable anti-inflammatory and anti-tumor effects, but the role of OA in cerebral ischemia-reperfusion injury (CIRI) has not been reported so far. Methods Oxygen and glucose deprivation/reoxygenation (OGD/R) model was induced in PC12 cells. MTT assay was used to detect the cell viability of PC12 cells, while ELISA assay detected the expression of TNF-α, IL-1β and IL-6. The expression of superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) was detected by the appropriate kits, and cell apoptosis by Tunel technique. Western blot assay detected the expression of apoptosis-related proteins. The cell transfection technique overexpressed miR-142‐5p. After overexpressing miR-142‐5p by cell transfection technique, the expression of miR-142‐5p was detected by RT-qPCR. Results Besides the ability to promote cell acitivity, OA ameliorated OGD/R-induced inflammatory response and apoptosis in PC12 cells. Moreover, the capability of OA to alleviate OGD/R-induced inflammation and apoptosis in PC12 cells was observed to be related to the down-regulation of miR-142‐5p. Conclusion OA improved inflammatory response and apoptosis of PC12 cells induced by OGD/R through downregulating miR-142‐5P

scholarly journals A Novel Method for Screening the Effective Compatibility Fractions of Naomaitong for the Treatment of Cerebral Ischemic Stroke Using Support Vector Machine Model

2020 ◽  
Author(s):  
Huanzheng Yu ◽  
Qiu Liu ◽  
Huiting Zheng ◽  
Minghua Xian ◽  
Shengwang Liang ◽  
...  
Keyword(s):  
Support Vector Machine ◽  
Ischemic Stroke ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Support Vector ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Abstract Background: Screening the fractions of traditional Chinese medicine (TCM) medications effective against a disease without affecting their compatibility is a major challenge. Therefore, the goal of the present study was to establish a novel methodology for screening the bioactive fractions of Naomaitong (NMT) utilizing the Support Vector Machine (SVM) model. Methods: The extract of NMT was separated into 21 fractions using macroporous resin. The different combinations of elution fractions were selected using the Plackett-Burman method and used as an input value for SVM. Infarct size in the rat model of cerebral ischemia-reperfusion injury and the content of selected compounds measured by HPLC were used as output vectors of the SVM training set. Based on the SVM target model, the optimal combination of elution fractions was predicted and verified in the rat model of ischemia-reperfusion injury. Results: The effective compatibility of NMT was screened by SVM simulation: all elution fractions of rhubarb, 30%, 60%, and 95% ethanol elution fractions of ginseng, and 30% and 60% ethanol elution fractions of puerarin and chuanxiong. The optimization of compatibility fractions of NMT was found to have the same protective efficacy in cerebral ischemia-reperfusion injury in rats. Conclusions: The performed analysis established a novel SVM-based method for screening the compatibility fractions of NMT effective against cerebral ischemic stroke injury. The results provide a new methodology for the optimization of the compatibility of TCM compounds and the discovery of effective components.

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