Publications by authors named "Xun-Ming Ji"

57 Publications

Thrombolytic DNT and fatality and disability rates in acute ischemic stroke: a study from Bigdata Observatory Platform for Stroke of China.

Neurol Sci 2021 Sep 3. Epub 2021 Sep 3.

The General Office of Stroke Prevention Project Committee, National Health Commission of the People's Republic of China, No. 118, Guang'anmen Inner Street, Beijing, 100053, China.

Objective: To evaluate whether shorter door-to-needle times (DNT) with intravenous tissue plasminogen activator (tPA) for acute ischemic stroke are associated with improved 1-year outcomes in Chinese patients.

Methods: From August to September 2019, all first-ever ischemic stroke patients who were treated with intravenous tPA within 4.5 h of the time they were last known to be well from 232 hospitals in China were included. Patients were divided into four groups according to DNT time (≤ 45 min; 45-60 min; 60-90 min; > 90 min). All discharged patients would receive a telephone follow-up at 12-month after admission. Death and disability events were recorded.

Results: Finally, 2370 patients were analyzed. The median age was 65 years, 66.6% were male, and 2.4% were of ethnic minorities. In the 1-year follow-up, 211 patients died (8.9%; 95%CI: 7.8-10.0%). The patients (53.1%) had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year mortality (8.9% vs 8.9% [absolute difference, 0.03% {95% CI, - 0.05% to - 0.10%}, odd ratio {OR}, 1.00 {95% CI, 0.75 to 1.33}]). In addition, 385 patients (16.2%; 14.8-17.3%) out of those survivors had disability events. The patients had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year disability rate (18.9% vs 16.7% [absolute difference, 1.9% {95% CI, 1.1% to 3.0%}, odd ratio {OR}, 1.22 {95% CI, 0.89 to 1.43}]).

Conclusions: The results did not show that shorter DNT for tPA administration was significantly associated with better 1-year outcomes.
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http://dx.doi.org/10.1007/s10072-021-05580-wDOI Listing
September 2021

Case-fatality, disability and recurrence rates after first-ever stroke: A study from bigdata observatory platform for stroke of China.

Brain Res Bull 2021 Oct 27;175:130-135. Epub 2021 Jul 27.

The General Office of Stroke Prevention Project Committee, National Health Commission of the People's Republic of China, Beijing, China. Electronic address:

Background: There is currently a lack of data on stroke hospitalizations and long-term outcomes in China. Therefore, we investigated 12-month stroke fatality, disability, and recurrence rates after the first-ever stroke.

Methods: This was a prospective nationwide hospital-based cohort study. From August to September 2019, all patients with first-ever stroke (ischemic stroke [IS], intracerebral hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) and with symptom onset within 14 days from 232 hospitals were included. Case fatality, disability, and recurrence rates for one year were estimated.

Results: In total, 36250 first-ever stroke patients from 194 hospitals were recruited (median age was 65(IQR, 56-73) years and 61.4 % were male). The rate of intravenous thrombolysis and endovascular treatment for IS were 9.5 % and 4.4 %, respectively. In-hospital death rate was 1.9 % (95 %CI: 1.7 %-2.0 %) for stroke inpatients, ranging from 0.9 % (0.8 %-1.1 %) for IS to 5.1 % (4.6 %-5.6 %) for ICH. The 12-month fatality rate was 8.6 % (95 %CI: 8.3 %-8.9 %) for discharged stroke patients, ranging from 6.0 % (5.7 %-6.3 %) for IS to 17.7 % (16.7 %-18.7 %) for ICH. The 12-month disability rate was 16.6 % (95 %CI: 16.2 %-17.0 %) for stroke survivors, ranging from 11.1 % (9.3 %-12.8 %) for SAH to 29.2 % (27.9 %-30.4 %) for ICH. The stroke recurrence rate was 5.7 % (5.5 %-6.0 %) for stroke survivors, ranging from 2.5 % (1.7 %-3.3 %) for SAH to 6.4 % (6.0 %-6.7 %) for IS.

Conclusion: Our results support the hypothesis that the prognosis of Chinese stroke patients appears to have improved and is not very bad.
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http://dx.doi.org/10.1016/j.brainresbull.2021.07.020DOI Listing
October 2021

Normobaric oxygen may correct chronic cerebral ischemia-mediated EEG anomalies.

CNS Neurosci Ther 2021 Oct 9;27(10):1214-1223. Epub 2021 Jul 9.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Aims: To explore the safety and efficacy of normobaric oxygen (NBO) on correcting chronic cerebral ischemia (CCI) and related EEG anomalies.

Methods: This prospective randomized trial (NCT03745092) enrolled 50 cases of CCI patients, which were divided into NBO (8 L/min of oxygen supplement) group and control group (room air) randomly, and also enrolled 21 healthy volunteers. Two times of 30-min EEG recordings with the interval of 45min of NBO or room air were analyzed quantitatively.

Results: The CCI-mediated EEG presented with two patterns of electrical activities: high-power oscillations (high-power EEG, n = 26) and paroxysmal slow activities under the normal-power background (normal-power EEG, n = 24). The fronto-central absolute power (AP) of the beta, alpha, theta, and delta in the high-power EEG was higher than that in healthy EEG (p < 0.05). The fronto-central theta/alpha, delta/alpha and (delta + theta)/(alpha + beta) ratios in the normal-power EEG were higher than those in healthy EEG (p < 0.05). The high-power EEG in NBO group had higher fronto-central AP reduction rates than those in control group (p < 0.05). NBO remarkably reduced the fronto-central theta/alpha, delta/alpha, and (delta + theta)/(alpha + beta) ratios in the normal-power EEG (p < 0.05).

Conclusions: NBO rapidly ameliorates CCI-mediated EEG anomalies, including attenuation of the abnormal high-power oscillations and the paroxysmal slow activities associated with CCI.
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http://dx.doi.org/10.1111/cns.13703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446210PMC
October 2021

High-Resolution Magnetic Resonance Black Blood Thrombus Imaging and Serum D-Dimer in the Confirmation of Acute Cortical Vein Thrombosis.

Front Neurol 2021 21;12:680040. Epub 2021 Jun 21.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Cerebral cortical vein thrombosis (CCVT) is often misdiagnosed because of its non-specific diagnostic symptoms. Here, we analyzed a cohort of patients with CCVT in hopes of improving understandings and treatments of the disease. A total of 23 patients with CCVT (confirmed with high-resolution imaging), who had been diagnosed between 2017 and 2019, were enrolled in this cohort study. Baseline demographics, clinical manifestations, laboratory data, radiological findings, treatment, and outcomes were collected and analyzed. Fourteen females and nine males were enrolled (mean age: 32.7 ± 11.9 years), presenting in the acute (within 7 days, = 9), subacute (8-30 days, = 7), and chronic (over 1 month, = 7) stages. Headaches (65.2%) and seizures (39.1%) were the most common symptoms. Abnormally elevated plasma D-dimers were observed in the majority of acute stage patients (87.5%). The diagnostic accuracy of contrast-enhanced magnetic resonance venography (CE-MRV) and high-resolution magnetic resonance black-blood thrombus imaging (HR-MRBTI) in detecting CCVT were 57.1 and 100.0%, respectively. All patients had good functional outcomes after 6-month of standard anticoagulation (mRS 0-1) treatment. However, four CCVT patients that had cases involving multiple veins showed symptom relief after batroxobin therapy ( = 0.030). HR-MRBTI may be a fast and accurate tool for non-invasive CCVT diagnosis. HR-MRBTI combined with D-dimer can also precisely identify the pathological stage of CCVT. Batroxobin may safely accelerate cortical venous recanalization in combination with anticoagulation. Follow-up studies with larger sample sizes are suggested to evaluate the safety and efficacy of batroxobin for treating CCVT.
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http://dx.doi.org/10.3389/fneur.2021.680040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255931PMC
June 2021

Stroke-unit care for stroke patients in China: the results from Bigdata Observatory platform for Stroke of China.

J Neurol 2021 Apr 22. Epub 2021 Apr 22.

The General Office of Stroke Prevention Project Committee, National Health Commission of the People's Republic of China, Beijing, China.

Background: To assess whether stroke patients admitted to stroke units (SU) have a better short-term outcome than those treated in conventional wards (CW).

Methods: A total of 20 hospitals from 16 provinces in China were initially selected in this study. Finally, 24,090 consecutive admissions in 2013-2015 treated in CW and 21,332 consecutive entries in 2017-2019 treated in SU were included. The primary endpoint of this study was the all-cause death or dependency condition three months after admission.

Results: Patients in the SU group were more likely receiving thrombolytic therapy (3.9 vs 2.1%) and intravascular treatment (1.2 and 0.7%). In-hospital death were lower in the SU group than the CW group (SU vs CW: 2.93 vs 4.58% [absolute difference, - 2.28% {95% CI, - 3.32% to - 0.93%}, odd ratio {OR}, 0.72{95% CI, 0.61 to 0.82}]. Death after discharge was also lower in the SU group than the CW (SU vs CW: 5.07 vs 6.72% [absolute difference, - 2.33% {95% CI, - 3.39% to - 0.90%}, odd ratio {OR}, 0.75{95% CI, 0.68 to 0.84}]. In addition, patients who received SU care were less likely to be dead or disabled than those patients who received CW care after adjusting for other variability (SU vs CW: 36.20 vs 44.33% [absolute difference, - 11.33% {95% CI, - 15.32% to - 7.14%}, odd ratio {OR}, 0.78{95% CI, 0.80 to 0.85}].

Conclusions: Among patients with stroke, admission to a designated SU was associated with modestly lower mortality at discharge, reduced probability of death, or being disabled at the end of follow-up.
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http://dx.doi.org/10.1007/s00415-021-10532-7DOI Listing
April 2021

Clinical characteristics, inflammation and coagulation status in patients with immunological disease-related chronic cerebrospinal venous insufficiency.

Ann Transl Med 2021 Feb;9(3):236

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Immunological disease-related chronic cerebrospinal venous insufficiency (CCSVI) is rarely reported. This study aimed to analyze clinical characteristics, inflammation, and coagulation status in patients with immunological disease-related CCSVI.

Methods: Patients with CCSVI were enrolled from 2017 to 2019 and divided into three cohorts based on their immunological disease backgrounds, including groups with confirmed autoimmune disease, with suspected/subclinical autoimmune disease, and with non-immunological etiology. Immunological, inflammatory, and thrombophilia biomarker assay in blood samples were obtained. Mann-Whitney U test or Fisher's exact test was used to compare continuous variables or categorical variables between the CCSVI patients with or without the immunological etiology. Spearman's correlation analysis was conducted among age, baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), interleukin-6 (IL-6), C-reactive protein (CRP), and neuron-specific enolase (NSE) in the three groups.

Results: A total of 255 consecutive patients with CCSVI were enrolled, including three subgroups: CCSVI with confirmed autoimmune disease (n=41), CCSVI with suspected/subclinical autoimmune disease (n=116) and CCSVI with non-immunological etiology (n=98). In the first subgroup, a series of 41 cases was confirmed with eight different autoimmune diseases including antiphospholipid syndrome (n=18), Sjögren's syndrome (n=8), immunoglobulin G4-related disease (n=7), Behçet's disease (n=2), autoimmune hepatitis (n=2), Wegener's granulomatosis (n=2), systemic sclerosis (n=1) and AQP4 antibody-positive neuromyelitis optica spectrum disorder (n=1). Groups with immunological etiology did not show a higher incidence of thrombophilia or increased pro-inflammatory biomarkers (e.g., neutrophil, IL-6). However, patients with non-immunological etiology had a higher baseline level of CRP. Additionally, baseline PLR was moderately correlated to NLR and CRP in CCSVI patients with non-immunological etiology and suspected/subclinical autoimmune disease.

Conclusions: The formation of CCSVI may be based on the inflammatory process, facilitated by multiple risk factors, among which medical history of immunological diseases may play a significant role due to the intricate relationship between inflammation and coagulation. Moreover, CCSVI may also cause an independent inflammatory injury in venous walls, leading to focal stenosis or thrombus, without attacks from autoimmune antibodies.
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http://dx.doi.org/10.21037/atm-20-4201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940939PMC
February 2021

Cyclosporine-A-Induced Intracranial Thrombotic Complications: Systematic Review and Cases Report.

Front Neurol 2020 11;11:563037. Epub 2021 Feb 11.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

This study reported two cases of intracranial thrombotic events of aplastic anemia (AA) under therapy with cyclosporine-A (CsA) and reviewed both drug-induced cerebral venous thrombosis (CVT) and CsA-related thrombotic events systematically. We searched PubMed Central (PMC) and EMBASE up to Sep 2019 for publications on drug-induced CVT and Cs-A-induced thrombotic events. Medical subject headings and Emtree headings were used with the following keywords: "cyclosporine-A" and "cerebral venous thrombosis OR cerebral vein thrombosis" and "stroke OR Brain Ischemia OR Brain Infarction OR cerebral infarction OR intracerebral hemorrhage OR intracranial hemorrhage." We found that CsA might be a significant risk factor in inducing not only CVT but also cerebral arterial thrombosis in patients with AA.
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http://dx.doi.org/10.3389/fneur.2020.563037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906016PMC
February 2021

The antiphospholipid syndrome may induce non-thrombotic internal jugular vein stenosis: two cases report.

BMC Neurol 2021 Jan 7;21(1). Epub 2021 Jan 7.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Chang Chun road 45, Xicheng, Beijing, China.

Background: Antiphospholipid syndrome (APS) is associated with a high incidence of thrombotic events, either arterial thrombosis or venous thrombosis. However, APS-related non-thrombotic venous stenosis is rarely reported.

Case Presentation: This study described two cases of young women with APS-related internal jugular vein stenosis (IJVS) and reviewed current literature on this issue, including clinical features, diagnosis, and treatment.

Conclusions: IJVS is a rather rare complication of APS. Two cases were reported for the first time that high titer of antiphospholipid antibodies (aPL) might mediate direct vessel wall damage and further induce venous stenosis despite long-term standardized anticoagulation to prevent thrombus formation. Therefore, dynamic monitoring of autoantibodies and concomitant use of anticoagulants and corticosteroids may be necessary to the management of APS and its complications.
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http://dx.doi.org/10.1186/s12883-020-02035-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789703PMC
January 2021

Stroke prevention and control system in China: CSPPC-Stroke Program.

Int J Stroke 2021 04 29;16(3):265-272. Epub 2020 Mar 29.

The General Office of Stroke Prevention Project Committee, National Health Commission of the People's Republic of China, Beijing, China.

In China, stroke is a major cause of mortality, and long-term physical and cognitive impairment. To meet this challenge, the Ministry of Health China Stroke Prevention Project Committee (CSPPC) was established in April 2011. This committee actively promotes stroke prevention and control in China. With government financial support of 838.4 million CNY, 8.352 million people from 536 screening points in 31 provinces have received stroke screening and follow-up over the last seven years (2012-2018). In 2016, the CSPPC issued a plan to establish stroke centers. To shorten the pre-hospital period, the CSPPC established a stroke center network, stroke map, and stroke "Green Channel" to create three 1-h gold rescue circles, abbreviated as "1-1-1" (onset to call time <1 h; pre-hospital transfer time < 1 h, and door-to-needle time < 1 h). From 2017 to 2018, the median door-to-needle time dropped by 4.0% (95% confidence interval (CI), 1.4-9.4) from 50 min to 48 min, and the median onset-to-needle time dropped by 2.8% (95% CI, 0.4-5.2) from 180 min to 175 min. As of 31 December 2018, the CSPPC has established 380 stroke centers in mainland China. From 1 November 2018, the CSPPC has monitored the quality of stroke care in stroke center hospitals through the China Stroke Data Center Data Reporting Platform. The CSPPC Stroke program has led to a significant improvement in stroke care. This program needs to be further promoted nationwide.
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http://dx.doi.org/10.1177/1747493020913557DOI Listing
April 2021

Long-term outcomes of axillary to carotid bypass for symptomatic patients with chronic common carotid artery occlusion.

J Vasc Surg 2020 08 25;72(2):597-602. Epub 2019 Dec 25.

Department of Vascular Surgery, XuanWu Hospital, Capital Medical University, Beijing, China.

Objective: Relatively little is known about the natural history of atherosclerotic common carotid artery occlusion and optimal treatment of these patients is still unclear. The aim of this retrospective study was to evaluate the immediate- and long-term outcomes of axillary to carotid bypass with polytetrafluoroethylene graft for symptomatic patients with chronic common carotid artery occlusion.

Methods: From March 2001 to December 2017, 58 symptomatic patients (41 men; mean age 64.7 years) with chronic common carotid artery occlusion underwent axillary to carotid bypass at one academic hospital. The clinical data of this patient cohort were retrospectively analyzed. The cumulative graft patency, overall survival, freedom from symptoms, and freedom from ipsilateral stroke were calculated with Kaplan-Meier method.

Results: Thirty-three patients presented with transient ischemic attack and 25 patients presented with minor stroke. At 30 days after bypass, the overall perioperative complication rate was 3.4% (2/58). Mild injuries of brachial plexus occurred in one (1.7%) patient and myocardial infarction occurred in one (1.7%) patient. No perioperative stroke or death occurred. The median follow-up was 51 months (range, 12-203) for this series. The cumulative graft patency rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 83%, respectively. The cumulative freedom from symptoms rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 75%, respectively. The cumulative freedom from ipsilateral stroke rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 82%, respectively. The overall survival rates at 1, 3, 5, and 10 years were 98%, 89%, 81%, and 67%, respectively.

Conclusions: Axillary to carotid bypass with polytetrafluoroethylene graft is safe and durable for symptomatic patients with chronic common carotid artery occlusion. The results of this study should be confirmed with a larger, randomized controlled trial in future.
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http://dx.doi.org/10.1016/j.jvs.2019.10.059DOI Listing
August 2020

Remote ischemic conditioning for the treatment of ischemic moyamoya disease.

CNS Neurosci Ther 2020 05 8;26(5):549-557. Epub 2019 Dec 8.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Aims: This study investigated the safety and efficacy of remote ischemic conditioning (RIC) on ameliorating the sequelae of ischemic moyamoya disease (iMMD).

Methods: A total of 30 iMMD patients underwent long-term RIC and were followed up at 0.5, 1, and 2 years for clinical outcomes, including frequency of stroke recurrence, Patient Global Impression of Change (PGIC) scale, peak systolic velocities (PSV), and cerebral perfusion.

Results: During the whole RIC treatment process, no RIC-related adverse event occurred. Only one of 30 patients suffered a onetime infarction (3.3%), and the ratios of acceptable PGIC were 88.2%, 64.3%, and 92.3% at 0.5, 1, and 2 years follow-up. Kaplan-Meier analysis showed the frequency of stroke recurrence was significantly reduced after RIC (P = .013). The frequency of TIA per week was 1.1 (0.6, 2.8) prior to RIC and 0.1 (0.0, 0.5) post-RIC (P < .01). Compared to baseline, PSV values were significantly reduced after RIC treatment (P = .002 at 0.5, P = .331 at 1, and P = .006 at 2 years). In patients undergoing perfusion studies, 75% obtained improvement on followed-up SPECT and 95% on followed-up PET maps.

Conclusions: Remote ischemic conditioning may be beneficial on controlling iMMD-induced ischemic events, relieving symptoms, and improving cerebral perfusion, without incidence of complications in this case series.
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http://dx.doi.org/10.1111/cns.13279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163773PMC
May 2020

Cognitive improvement after carotid artery stenting in patients with symptomatic internal carotid artery near-occlusion.

J Neurol Sci 2019 Sep 19;404:86-90. Epub 2019 Jul 19.

Department of Vascular Surgery, XuanWu Hospital, Capital Medical University, Beijing, China.

Background And Purpose: To investigate the influence of carotid artery stenting (CAS) with embolic protection device (EPD) on the cognitive function of patients with near-occlusion of the cervical internal carotid artery (ICA).

Methods: From February 2014 to December 2017, a total of 79 symptomatic patients were recruited in this study. Of these patients, 31 patients refused to receive CAS therapy. They were divided into the CAS group (48 patients) and the medical treatment group (31 patients). Montreal cognitive assessment (MoCA) instrument was used for the evaluation of cognitive function. The analyzed endpoints included cumulative 12 month incidence of ipsilateral ischemic cerebrovascular events and MoCA scores at 1 month and 12 months after treatment.

Results: Cumulative 12 months incidence of ipsilateral ischemic cerebrovascular events was lower in patients who underwent CAS than in patients on medical treatment (P < 0.05). In CAS group, the total MoCA score, scores of attention and delayed recall at months 1 and 12 increased when compared with those at baseline (P < 0.05). In medical treatment group, the total MoCA score and attention score at month 12 decreased when compared with those at baseline (P < 0.05). In CAS group, the total MoCA score, scores of line connection test, drawing clock, attention and delayed recall were improved at 1 and 12 months when compared with medical treatment at the same time points (P < 0.05).

Conclusions: CAS with EPD not only decreases the risk of ipsilateral TIA and stroke but also may improve the cognitive function of symptomatic patients with ICA near-occlusion.
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http://dx.doi.org/10.1016/j.jns.2019.07.023DOI Listing
September 2019

MicroRNA expression in the hippocampal CA1 region under deep hypothermic circulatory arrest.

Neural Regen Res 2019 Nov;14(11):2003-2010

Department of Anesthesiology, Xuanwu Hospital, Capital Medical University; Institute of Geriatrics; National Clinical Research Center for Geriatric Disorders, Beijing, China.

Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs (miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection (cyclin dependent kinase, CDK16 and SLC1A2), central nervous system development (FOXO3, TYRO3, and SLC1A2), ion transmembrane transporter activity (ATP2B2 and SLC1A2), and interleukin-6 receptor binding (IL6R) - these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017 (approval No. XW-INI-AD2017-0112).
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http://dx.doi.org/10.4103/1673-5374.253174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676878PMC
November 2019

Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury.

Neural Regen Res 2019 Oct;14(10):1780-1786

China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.

Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury. Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering. The scaffolds were impregnated with rat bone marrow mesenchymal stem cells. A traumatic brain injury rat model was established using the 300 g weight free fall impact method. Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain. Modified neurological severity scores were used to assess the recovery of neurological function. The Morris water maze was employed to determine spatial learning and memory abilities. Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue. Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine (BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein. Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores, shortened the average latency of the Morris water maze, increased the number of platform crossings, diminished the degeneration of damaged brain tissue, and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas. At 14 days after transplantation, increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area. The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone. To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds, immunosuppressive cyclosporine was intravenously injected 12 hours before transplantation and 1-5 days after transplantation. The above indicators were similar to those of rats treated with bone marrow mesenchymal stem cells and collagen-chitosan scaffolds only. These findings indicate that transplantation of bone marrow mesenchymal stem cells in a collagen-chitosan scaffold can promote the recovery of neuropathological injury in rats with traumatic brain injury. This approach has the potential to be developed as a treatment for traumatic brain injury in humans. All experimental procedures were approved by the Institutional Animal Investigation Committee of Capital Medical University, China (approval No. AEEI-2015-035) in December 2015.
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http://dx.doi.org/10.4103/1673-5374.257533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585548PMC
October 2019

Cervical spondylotic internal jugular venous compression syndrome.

CNS Neurosci Ther 2020 01 22;26(1):47-54. Epub 2019 May 22.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Aims: This study aimed to identify the clinical profiles of cervical spondylosis-related internal jugular vein stenosis (IJVS) comprehensively.

Methods: A total of 46 patients, who were diagnosed as IJVS induced by cervical spondylotic compression were recruited. The clinical manifestations and imaging features of IJVS were presented particularly in this study.

Results: Vascular stenosis was present in 69 out of the 92 internal jugular veins, in which, 50.7% (35/69) of the stenotic vessels were compressed by the transverse process of C1, and 44.9% (31/69) by the transverse process of C1 combined with the styloid process. The transverse process of C1 compression was more common in unilateral IJVS (69.6% vs 41.3%, P = 0.027) while the transverse process of C1 combined with the styloid process compression had a higher propensity to occur in bilateral IJVS (52.2% vs 30.4%, P = 0.087). A representative case underwent the resection of the elongated left lateral mass of C1 and styloid process. His symptoms were ameliorated obviously at 6-month follow-up.

Conclusions: This study proposes cervical spondylotic internal jugular venous compression syndrome as a brand-new cervical spondylotic subtype. A better understanding of this disease entity can be of great relevance to clinicians in making a proper diagnosis.
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http://dx.doi.org/10.1111/cns.13148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930831PMC
January 2020

Batroxobin in combination with anticoagulation may promote venous sinus recanalization in cerebral venous thrombosis: A real-world experience.

CNS Neurosci Ther 2019 05 23;25(5):638-646. Epub 2019 Jan 23.

Departments of Neurology and Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Aims: The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation.

Methods: A total of 31 CVT patients were enrolled in this real-world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times.

Results: In the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61-40.7)] and segment-stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69-11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10-635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48-13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90-day follow-up (P > 0.05).

Conclusions: Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit.
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http://dx.doi.org/10.1111/cns.13093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488911PMC
May 2019

2-(2-Benzofuranyl)-2-imidazoline treatment within 5 hours after cerebral ischemia/reperfusion protects the brain.

Neural Regen Res 2018 Dec;13(12):2111-2118

Department of Neurosurgery; China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.

We previously demonstrated that administering 2-(2-benzofuranyl)-2-imidazolin (2-BFI), an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI (3 mg/kg) through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa's method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy . The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following: Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.
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http://dx.doi.org/10.4103/1673-5374.241461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199951PMC
December 2018

Brain-selective mild hypothermia promotes long-term white matter integrity after ischemic stroke in mice.

CNS Neurosci Ther 2018 12 16;24(12):1275-1285. Epub 2018 Sep 16.

Cerebrovascular Disease Research Institute, Xuanwu Hospital, Capital Medical University, Beijing, China.

Introduction: The neuroprotective effects of hypothermia in acute ischemic stroke are well documented. However, the mechanisms involved in the effects remain to be clearly elucidated and the role of hypothermia on long-term white matter integrity after acute ischemic stroke has yet to be investigated.

Aims: To investigate the role of mild focal hypothermia on long-term white matter (WM) integrity after transient cerebral ischemia.

Results: Mild focal hypothermia treatment immediately after ischemic stroke significantly promotes WM integrity 28 days after the occlusion of the middle cerebral artery (MCAO) in mice. Higher integrity of white matter, lower activation of total microglia, less infarct volume, and better neurobehavioral function were detected in hypothermia-treated mice compared to normothermia-treated mice. Furthermore, we found that hypothermia could decrease detrimental M1 phenotype microglia and promote healthy M2 phenotype microglia. In vitro, results also indicated that hypothermia promoted oligodendrocytes differentiation and maturation after oxygen glucose deprivation.

Conclusion: Hypothermia promotes long-term WM integrity and inhibits neuroinflammation in a mouse model of ischemic brain injury.
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http://dx.doi.org/10.1111/cns.13061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489965PMC
December 2018

Understanding jugular venous outflow disturbance.

CNS Neurosci Ther 2018 06 23;24(6):473-482. Epub 2018 Apr 23.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Extracranial venous abnormalities, especially jugular venous outflow disturbance, were originally viewed as nonpathological phenomena due to a lack of realization and exploration of their feature and clinical significance. The etiology and pathogenesis are still unclear, whereas a couple of causal factors have been conjectured. The clinical presentation of this condition is highly variable, ranging from insidious to symptomatic, such as headaches, dizziness, pulsatile tinnitus, visual impairment, sleep disturbance, and neck discomfort or pain. Standard diagnostic criteria are not available, and current diagnosis largely depends on a combinatory use of imaging modalities. Although few researches have been conducted to gain evidence-based therapeutic approach, several recent advances indicate that intravenous angioplasty in combination with stenting implantation may be a safe and efficient way to restore normal blood circulation, alleviate the discomfort symptoms, and enhance patients' quality of life. In addition, surgical removal of structures that constrain the internal jugular vein may serve as an alternative or adjunctive management when endovascular intervention is not feasible. Notably, discussion on every aspect of this newly recognized disease entity is in the infant stage and efforts with more rigorous designed, randomized controlled studies in attempt to identify the pathophysiology, diagnostic criteria, and effective approaches to its treatment will provide a profound insight into this issue.
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http://dx.doi.org/10.1111/cns.12859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489808PMC
June 2018

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning.

Chin Med J (Engl) 2018 Feb;131(3):347-351

Department of Neurology, Medical University of South Carolina, Charleston, SC 29403, USA.

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA.

Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes.

Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA.

Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820.
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http://dx.doi.org/10.4103/0366-6999.223849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798057PMC
February 2018

Advances in chronic cerebral circulation insufficiency.

CNS Neurosci Ther 2018 Jan 15;24(1):5-17. Epub 2017 Nov 15.

Departments of Neurology and Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Chronic cerebral circulation insufficiency (CCCI) may not be an independent disease; rather, it is a pervasive state of long-term cerebral blood flow insufficiency caused by a variety of etiologies, and considered to be associated with either occurrence or recurrence of ischemic stroke, vascular cognitive impairment, and development of vascular dementia, resulting in disability and mortality worldwide. This review summarizes the features and recent progress of CCCI, mainly focusing on epidemiology, experimental research, pathophysiology, etiology, clinical manifestations, imaging presentation, diagnosis, and potential therapeutic regimens. Some research directions are briefly discussed as well.
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http://dx.doi.org/10.1111/cns.12780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489997PMC
January 2018

Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective.

Med Gas Res 2016 Jul-Sep;6(3):147-153. Epub 2016 Oct 14.

Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Acute ischemic stroke is a common and serious neurological disease. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve outcomes after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBO), an easily applicable and non-invasive method, shows protective effects on acute ischemic stroke animals and patients in pilot studies. However, many critical scientific questions are still unclear, such as the therapeutic time window of NBO, the long-term effects and the benefits of NBO in large clinic trials. In this article, we review the current literatures on NBO treatment of acute ischemic stroke in preclinical and clinical studies and try to analyze and identify the key gaps or unknowns in our understanding about NBO. Based on these analyses, we provide suggestions for future studies.
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http://dx.doi.org/10.4103/2045-9912.191360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110139PMC
October 2016

Association between serum cystatin C levels and the severity or potential risk factors of acute ischemic stroke.

Neurol Res 2016 Jun;38(6):518-23

b Department of Neurology , Second Affiliated Hospital of Nantong University , Nantong , China.

Objective: We sought to investigate whether serum cystatin C levels are correlated with either stroke severity or with potential risk factors of acute ischemic stroke.

Methods: 171 patients with acute ischemic stroke and 99 control subjects with minor, unrelated diseases with stroke were included in this retrospective study. Serum cystatin C levels were determined in all subjects. Serum concentrations of several vascular risk factors in stoke patients were determined by biochemical assays. The severity of strokes was scored via the National Institutes of Health Stroke Scale (NIHSS).

Results: Serum cystatin C levels were significantly increased in patients with acute ischemic stroke compared with control subjects (1.26 ± 0.34 mg/L vs. 0.78 ± 0.24 mg/L, p < 0.001).When analyzed in quartiles of serum cystatin C levels, concentrations were low (<0.75 mM) for 5 stroke patients (2.92%), intermediate (0.75-1 mM) for 42 patients (24.56%), high (1-1.25 mM) for 45 patients (26.32%), and very high (>1.25 mM) for 79 patients (46.20%). However, serum cystatin C levels were not correlated with NIHSS scores, serum total cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein a, or apolipoprotein b levels. Further, serum cystatin C concentrations in stroke patients were not correlated with the presence of intracranial arterial stenosis, hypertension, or diabetes.

Conclusion: Our study suggests that there is a close relationship between cystatin C and acute ischemic stroke, independently of conventional risk factors. But the levels of cystatin C are not correlated with the stroke severity.
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http://dx.doi.org/10.1080/01616412.2016.1187825DOI Listing
June 2016

Generalization of the Right Acute Stroke Prevention Strategies in Reducing in-Hospital Delays.

PLoS One 2016 6;11(5):e0154972. Epub 2016 May 6.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

The aim of this study was to reduce the door-to-needle (DTN) time of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) through a comprehensive, hospital-based implementation strategy. The intervention involved a systemic literature review, identifying barriers to rapid IVT treatment at our hospital, setting target DTN time intervals, and building an evolving model for IVT candidate selection. The rate of non-in-hospital delay (DTN time ≤ 60 min) was set as the primary endpoint. A total of 348 IVT cases were enrolled in the study (202 and 146 in the pre- and post-intervention group, respectively). The median age was 61 years in both groups; 25.2% and 26.7% of patients in the pre- and post-intervention groups, respectively, were female. The post-intervention group had higher rates of dyslipidemia and minor stroke [defined as National Institutes of Health Stroke Scale (NIHSS) ≤ 3]; less frequent atrial fibrillation; higher numbers of current smokers, heavy drinkers, referrals, and multi-model head imaging cases; and lower NIHSS scores and blood sugar level (all P < 0.05). All parameters including DTN, door-to-examination, door-to-imaging, door-to-laboratory, and final-test-to-needle times were improved post-intervention (all P < 0.05), with net reductions of 63, 2, 4, 28, and 23 min, respectively. The rates of DTN time ≤ 60 min and onset-to-needle time ≤ 180 min were significantly improved by the intervention (pre: 9.9% vs. post: 60.3%; P < 0.001 and pre: 23.3% vs. post: 53.4%; P < 0.001, respectively), which was accompanied by an increase in the rate of neurological improvement (pre: 45.5% vs. post: 59.6%; P = 0.010), while there was no change in incidence of mortality or systemic intracranial hemorrhage at discharge (both P > 0.05). These findings indicate that it is possible to achieve a DTN time ≤ 60 min for up to 60% of hospitals in the current Chinese system, and that this logistical change can yield a notable improvement in the outcome of IVT patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154972PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859531PMC
July 2017

Luoyutong Treatment Promotes Functional Recovery and Neuronal Plasticity after Cerebral Ischemia-Reperfusion Injury in Rats.

Evid Based Complement Alternat Med 2015 1;2015:369021. Epub 2015 Dec 1.

Cerebrovascular Diseases Research Institute, Xuanwu Hospital, Capital Medical University, Ministry of Education, 45 Changchun Street, Beijing 100053, China ; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, 45 Changchun Street, Beijing 100053, China.

Luoyutong (LYT) capsule has been used to treat cerebrovascular diseases clinically in China and is now patented and approved by the State Food and Drug Administration. In this retrospective validation study we investigated the ability of LYT to protect against cerebral ischemia-reperfusion injury in rats. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion followed by reperfusion. Capsule containing LYT (high dose and medium dose) as treatment group and Citicoline Sodium as positive control treatment group were administered daily to rats 30 min after reperfusion. Treatment was continued for either 3 days or 14 days. A saline solution was administered to control animals. Behavior tests were performed after 3 and 14 days of treatment. Our findings revealed that LYT treatment improved the neurological outcome, decreased cerebral infarction volume, and reduced apoptosis. Additionally, LYT improved neural plasticity, as the expression of synaptophysin, microtubule associated protein, and myelin basic protein was upregulated by LYT treatment, while neurofilament 200 expression was reduced. Moreover, levels of brain derived neurotrophic factor and basic fibroblast growth factor were increased. Our results suggest that LYT treatment may protect against ischemic injury and improve neural plasticity.
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http://dx.doi.org/10.1155/2015/369021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678236PMC
December 2015

Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury.

Neural Regen Res 2015 Sep;10(9):1471-6

Hypoxia Medical Institute, Xuanwu Hospital, Capital Medical University, Beijing, China.

Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats.
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http://dx.doi.org/10.4103/1673-5374.165519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625514PMC
September 2015

Gabapentin Effects on PKC-ERK1/2 Signaling in the Spinal Cord of Rats with Formalin-Induced Visceral Inflammatory Pain.

PLoS One 2015 29;10(10):e0141142. Epub 2015 Oct 29.

Hypoxia Medical Institute, Xuanwu Hospital, Capital Medical University, Beijing, China.

Currently, the clinical management of visceral pain remains unsatisfactory for many patients suffering from this disease. While preliminary animal studies have suggested the effectiveness of gabapentin in successfully treating visceral pain, the mechanism underlying its analgesic effect remains unclear. Evidence from other studies has demonstrated the involvement of protein kinase C (PKC) and extracellular signal-regulated kinase1/2 (ERK1/2) in the pathogenesis of visceral inflammatory pain. In this study, we tested the hypothesis that gabapentin produces analgesia for visceral inflammatory pain through its inhibitory effect on the PKC-ERK1/2 signaling pathway. Intracolonic injections of formalin were performed in rats to produce colitis pain. Our results showed that visceral pain behaviors in these rats decreased after intraperitoneal injection of gabapentin. These behaviors were also reduced by intrathecal injections of the PKC inhibitor, H-7, and the ERK1/2 inhibitor, PD98059. Neuronal firing of wide dynamic range neurons in L6-S1 of the rat spinal cord dorsal horn were significantly increased after intracolonic injection of formalin. This increased firing rate was inhibited by intraperitoneal injection of gabapentin and both the individual and combined intrathecal application of H-7 and PD98059. Western blot analysis also revealed that PKC membrane translocation and ERK1/2 phosphorylation increased significantly following formalin injection, confirming the recruitment of PKC and ERK1/2 during visceral inflammatory pain. These effects were also significantly reduced by intraperitoneal injection of gabapentin. Therefore, we concluded that the analgesic effect of gabapentin on visceral inflammatory pain is mediated through suppression of PKC and ERK1/2 signaling pathways. Furthermore, we found that the PKC inhibitor, H-7, significantly diminished ERK1/2 phosphorylation levels, implicating the involvement of PKC and ERK1/2 in the same signaling pathway. Thus, our results suggest a novel mechanism of gabapentin-mediated analgesia for visceral inflammatory pain through a PKC-ERK1/2 signaling pathway that may be a future therapeutic target for the treatment of visceral inflammatory pain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141142PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626203PMC
June 2016

Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses.

CNS Neurosci Ther 2016 Jan 19;22(1):43-52. Epub 2015 Sep 19.

China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.

Aims: Remote ischemic preconditioning (RIPC) of a limb is a clinically feasible strategy to protect against ischemia-reperfusion injury after stroke. However, the mechanism underlying RIPC remains elusive.

Methods: We generated a rat model of noninvasive RIPC by four repeated cycles of brief blood flow constriction (5 min) in the hindlimbs using a tourniquet. Blood was collected 1 h after preconditioning and 3 days after brain reperfusion. The impact of RIPC on immune cell and cytokine profiles prior to and after transient middle cerebral artery occlusion (MCAO) was assessed.

Results: Remote ischemic preconditioning protects against focal ischemia and preserves neurological functions 3 days after stroke. Flow cytometry analysis demonstrated that RIPC ameliorates the post-MCAO reduction of CD3(+)CD8(+) T cells and abolishes the reduction of CD3(+)/CD161a(+) NKT cells in the blood. In addition, RIPC robustly elevates the percentage of B cells in peripheral blood, thereby reversing the reduction in the B-cell population after stroke. RIPC also markedly elevates the percentage of CD43(+)/CD172a(+) noninflammatory resident monocytes, without any impact on the percentage of CD43(-)/CD172a(+) inflammatory monocytes. Finally, RIPC induces IL-6 expression and enhances the elevation of TNF-α after stroke.

Conclusion: Our results reveal dramatic immune changes during RIPC-afforded neuroprotection against cerebral ischemia.
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http://dx.doi.org/10.1111/cns.12448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492849PMC
January 2016

Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis.

Chin Med J (Engl) 2015 Jul;128(13):1732-7

Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.

Background: Cerebral venous thrombosis (CVT) may lead to serious neurological disorders; however, little is known about the risk factors for recurrent CVT. Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol (HDL-C) levels with recurrent CVT.

Methods: This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital, Capital Medical University from August 2005 to September 2009. Demographic and clinical variables were collected, as well as laboratory parameters, including plasma fibrinogen and HDL-C. Patients with CVT were followed for recurrent symptomatic CVT. Follow-up was through the end of September 2010. Potential predictors of recurrence were analyzed using Cox survival analysis.

Results: At the end of the follow-up, 95 patients were eligible for the study. Twelve of 95 patients (12.6%) had recurred CVT. The median time of recurrence was 7 months (range: 1-39 months). Eight of these 12 (66.7%) experienced recurrence within the first 12 months after their initial CVT. The recurrence rate of CVT was 2.76 per 100 patient-years. Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen (>4.00 g/L) and low HDL-C (<1.08 mmol/L) levels at baseline was the only independent predictor for recurrent CVT (hazard ratio: 4.69; 95% confidence interval: 1.10-20.11; P < 0.05). Of the twelve patients with recurrent CVT in our study, 7 (58.3%) had high fibrinogen plus low HDL-C levels. All 7 of these patients took warfarin for 3-12 months, and 6 of 7 had recurrent CVT after the discontinuation of anticoagulant treatment.

Conclusions: Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.
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http://dx.doi.org/10.4103/0366-6999.159345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733709PMC
July 2015
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