Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the "energy chamber" of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.
Brain Ischemia/prevention & control* ; Calcium/metabolism* ; Humans ; Ischemic Stroke ; Mitochondria/pathology* ; Reactive Oxygen Species/metabolism* ; Reperfusion Injury/prevention & control*

Animals ; Berberine/therapeutic use* ; Brain Ischemia/prevention & control* ; Glutathione Peroxidase ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control*

In this research, high-throughput sequencing was used to investigate the mechanism of Naoxintong Capsules(NXTC) in prevention of post-ischemic inflammation. First, microglia BV-2 inflammatory model was induced by 1.0 μg·mL~(-1) LPS to investigate the effect of intestinal absorption solution of NXTC(NXTCIA) at different concentrations(62.5, 31.25, 15.63, 7.81 μg·mL~(-1)) on LPS-induced BV-2 inflammatory factors in microglia. Then, an RNA-Seq high-throughput sequencing method was performed to identify the differentially expressed mRNAs in microglia BV-2 after pre-treatment with NXTC. GO and KEGG enrichment analysis was used to screen the potential biological processes and related signaling pathways of NXTC in inhibiting inflammation. The results showed that four NXTCIA concentrations could significantly inhibit the release of LPS-induced inflammatory mediators in BV-2 in a dose-dependent manner. Furthermore, high-throughput sequencing results showed that 392 mRNA transcripts were reversed following pre-treatment with NXTC. GO enrichment analysis showed that the transcripts reversed by NXTC were mainly involved in Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway. Taken together, our findings showed that NXTC treatment could provide protective effects against inflammatory response and the mechanism might be related to the regulation of Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway.
Animals ; Capsules ; Drugs, Chinese Herbal/therapeutic use* ; Inflammation/prevention & control* ; Ischemia/complications* ; Lipopolysaccharides ; Mice ; Microglia/metabolism* ; RNA-Seq ; Transcriptome

BACKGROUND: High on-treatment platelet reactivity (HTPR) has been suggested as a risk factor for patients with ischemic vascular disease. We explored a predictive model of platelet reactivity to clopidogrel and the relationship with clinical outcomes. METHODS: A total of 441 patients were included. Platelet reactivity was measured by light transmittance aggregometry after receiving dual antiplatelet therapy. HTPR was defined by the consensus cutoff of maximal platelet aggregation >46% by light transmittance aggregometry. CYP2C19 loss-of-function polymorphisms were identified by DNA microarray analysis. The data were compared by binary logistic regression to find the risk factors. The primary endpoint was major adverse clinical events (MACEs), and patients were followed for a median time of 29 months. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the patients with HTPR and non-HTPR. RESULTS: The rate of HTPR was 17.2%. Logistic regression identified the following predictors of HTPR: age, therapy regimen, body mass index, diabetes history, CYP2C192, or CYP2C193 variant. The area under the curve of receiver operating characteristic for the HTPR predictive model was 0.793 (95% confidence interval: 0.738-0.848). Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE than those with non-HTPR (21.1% vs. 9.9%; χ = 7.572, P = 0.010). CONCLUSIONS Our results suggest that advanced age, higher body mass index, treatment with regular dual antiplatelet therapy, diabetes, and CYP2C192 or CYP2C193 carriers are significantly associated with HTPR to clopidogrel. The predictive model of HTPR has useful discrimination and good calibration and may predict long-term MACE.
Aged ; Blood Platelets ; drug effects ; Clopidogrel ; pharmacology ; therapeutic use ; Coronary Artery Disease ; metabolism ; prevention & control ; Cytochrome P-450 CYP2C19 ; metabolism ; Female ; Genotype ; Glycated Hemoglobin A ; metabolism ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Ischemia ; metabolism ; prevention & control ; Regression Analysis

BackgroundRemote ischemic postconditioning (RIPostC) appears to protect distant organs from ischemia-reperfusion injury (IRI). However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC.

MethodsCNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated.

ResultsA total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks (RR = 0.37; 95% CI: 0.26-0.55; P < 0.00001). Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score (MD: 1.96; 95% CI: 2.18-1.75; P < 0.00001), modified Rankin Scale score (MD: 0.73; 95% CI: 1.20-0.25; P = 0.00300), and high-sensitivity C-reactive protein (MD: 4.17; 95% CI: 4.71-3.62; P < 0.00001) between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration.

ConclusionThe present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI.

Brain Ischemia ; prevention & control ; Humans ; Ischemic Attack, Transient ; prevention & control ; therapy ; Ischemic Postconditioning ; methods ; Randomized Controlled Trials as Topic ; Stroke ; prevention & control

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Blood-Brain Barrier ; drug effects ; enzymology ; immunology ; Brain ; Brain Ischemia ; drug therapy ; enzymology ; genetics ; Caffeic Acids ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Lactates ; administration & dosage ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; genetics ; immunology ; prevention & control ; Salvia miltiorrhiza ; chemistry ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transcription Factor RelA ; genetics ; immunology

To investigate the protective effects of P2X7 receptor (P2X7R) inhibitor against cerebral ischemia/reperfusion (I/R) injury in rats and the possible mechanisms.
 Methods: The neurological deficit of rats was evaluated by Longa score. The infarct volume was examined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression levels of extracellular signal-regulated kinase (ERK), phosphorylation extracellular signal-regulated kinas p-ERK), connexin 43 (Cx43), Bax, Bcl-2 and cleaved caspase-3 were detected by Western blot.
 Results: Compared with sham group, the neurobehavioral score (P<0.05) and cerebral infarct volume (P<0.01) of rats in I/R group was increased. Compared with I/R group, brilliant blue G (BBG, the antagonist of P2X7R) or PD98059 (the inhibitor of EKR kinase) could reduce the neurobehavioral score (P<0.01) and cerebral infarct volume significantly (P<0.05). The neurobehavioral score and cerebral infarct volume was further decreased (P<0.05) when rats were treated with both BBG and PD98059. Compared with I/R group, the expression levels of p-ERK, Cx43, cleaved caspase-3 and the ratio of Bax/Bcl-2 were decreased by BBG or PD98059 pretreatment, and the protective effects were further enhanced when rats were treated with both BBG and PD98059 (P<0.05).
 Conclusion: Inhibition of P2X7R reduces the cerebral I/R injury of rats. ERK inhibition is probably involved in the protective effects of P2X7R inhibitor against cerebral I/R injury, which may be related to the reduction of Cx43 and cleaved caspase-3, and the ratio of Bax/Bcl-2.
Animals ; Brain Ischemia ; drug therapy ; prevention & control ; Gene Expression Regulation ; drug effects ; Phosphorylation ; drug effects ; Purinergic P2X Receptor Antagonists ; pharmacology ; therapeutic use ; Rats ; Receptors, Purinergic P2X7 ; Reperfusion Injury ; drug therapy ; prevention & control

OBJECTIVE: To investigate whether rapamycin treatment starting at 24 h after cerebral ischemia/reperfusion(I/R) has protective effect on brain injury in rats. METHODS: The rat I/R model was established by middle cerebral artery occlusion according to Longa's method. A total of 104 Sprague Dawley rats were randomly divided into sham group, model group, and rapamycin-treated groups (6 h or 24 h after modeling). Neurological function was assessed with neurological severity score (NSS). Triphenyl tetrazolium chloride (TTC) staining and Fluoro-Jade B (FJB) staining were used to examine the infarct volume and neuronal apoptosis, respectively. The expression of p-S6 protein in mTOR signaling pathway was detected by Western blot analysis. RESULTS: Compared with sham group, NSS of the model group was significantly increased and TTC staining indicated obvious infarct area (all <0.01). Furthermore, significantly increased number of FJB-positive cells and p-S6 expression in the penumbra area were shown in the model group (all <0.01). Compared with the model group, both rapamycin-treated groups demonstrated decreased NSS, infarction volume and FJB positive cells as well as p-S6 expression in the penumbra area (<0.05 or <0.01). There was no significant difference between the groups of rapamycin administrated 6 h and 24 h after modeling (all >0.05). CONCLUSIONS Rapamycin treatment starting at 24 h after I/R exhibits protective effect on brain injury in rats.
Animals ; Brain Ischemia ; drug therapy ; Immunosuppressive Agents ; therapeutic use ; Infarction, Middle Cerebral Artery ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Sirolimus ; therapeutic use ; Treatment Outcome

OBJECTIVE: To observe the effects of "" acupuncture on cerebral blood flow in high-risk patients of cerebral ischemic stroke based on arterial spin labeling (ASL) and perfusion-weighted imaging (PWI), and to evaluate the clinical efficacy. METHODS: A total of 180 patients with transient ischemic attacks (TIA) / minor ischemic stroke (MIS) were randomly divided into an acupuncture A group, an acupuncture B group and a medication group, 60 cases in each group. The patients in the acupuncture A group were treated with "" acupuncture at Baihui (GV 20), Fengfu (GV 16), Yamen (GV 15), Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Mingmen (GV 4), Yaoyangguan (GV 3) and Jingjiaji (EX-B 2), once a day; the patients in the acupuncture B group were treated with identical acupoints but was given once every other day; the patients in the medication group were treated with oral administration of nimodipine tablets, 30 mg, three times daily. All the three groups were treated for four weeks. ASL and PWI, including relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT) and relative time to peak (rTTP), were conducted before and after treatment; the changes of the test indexes were compared before and after treatment. The clinical efficacy of the three groups was compared. RESULTS: Compared before treatment, the numbers of ASL normal perfusion in the 3 groups were significantly increased after treatment (all <0.01); the number of ASL normal perfusion in the acupuncture A group was higher than that in the acupuncture B group (<0.05), but was not significantly different from that in the medication group (>0.05). Compared before treatment, rCBV and rCBF in the 3 groups were significantly increased after treatment (all <0.01), and rMTT and rTTP were significantly reduced (all <0.01). After treatment, rCBV and rCBF in the acupuncture A group were higher than those in the acupuncture B group (all <0.05); the rMTT and rTTP in the acupuncture A group were lower than those in the acupuncture B group (all <0.05); the differences of PWI parameters after treatment were not statistically significant between the acupuncture A group and medication group (all >0.05). The total effective rate was 88.3% (53/60) in the acupuncture A group, 73.3% (44/60) in the acupuncture B group and 90.0% (54/60) in the medication group; the total effective rate in the acupuncture A group was superior to that in the acupuncture B group (<0.05), but was not significantly different from that in the medication group (>0.05). CONCLUSION "" acupuncture could effectively improve the hypoperfusion of cerebral blood flow in patients with high risk of cerebral ischemic stroke, reduce the incidence of severe CIS; acupuncture for once a day is better than once every other day.
Acupuncture Therapy ; Brain Ischemia ; prevention & control ; Cerebrovascular Circulation ; Humans ; Risk Factors ; Stroke

BACKGROUND AND OBJECTIVES: The Korean Organ Transplant Registry (KOTRY), which was the first national transplant registry in Korea, was founded by the Korean Society for Transplantation and the Korean Center for Disease Control in 2014. Here, we present the initial report of the Korean Heart Transplant Registry. METHODS: A total of 183 heart transplantation (HTPL) patients performed at 4 nationally representative hospitals were collected from April 2014 to December 2015. We analyzed donor and recipient characteristics, treatment patterns, and immediate post-transplantation outcomes. RESULTS: One hundred and eighty-three patients were enrolled. The mean age of the patients was 50.5±13.5 years. The mean age of the male recipients was 4 years greater than that of the female recipients (51.7±13.3 years vs. 47.9±13.7 years, p < 0.050). The mean age of donors was more than 12 years younger than that of heart recipients (37.6±10.1 years). Dilated cardiomyopathy was the predominant cause (69%) of heart failure in recipients, followed by ischemic heart diseases (14%) and valvular heart disease (4%). Rejection episodes were most frequent in the 1–6-month period after transplantation (48%), and rarely required intensive treatment. Infection episodes were most frequent <1 month after transplantation (66%) and bacterial and viral infections were equally reported. The 1-year survival rate was 91.6% and most mortality cases occurred during the perioperative period within 1 month after transplantation. CONCLUSION: With the establishment of the KOTRY in 2014, it is now possible to present nationwide epidemiological data for HTPL in Korea for the first time. The KOTRY is the first national HTPL registry in Korea, and will continue until 2023.
Cardiomyopathy, Dilated ; Centers for Disease Control and Prevention (U.S.) ; Female ; Heart Failure ; Heart Transplantation* ; Heart Valve Diseases ; Heart* ; Humans ; Korea ; Male ; Mortality ; Myocardial Ischemia ; Perioperative Period ; Registries ; Survival Rate ; Tissue Donors ; Transplants*