Time filter

Source Type

Seattle, WA, United States

Tian Y.,Tianjin Medical University | Tian Y.,Puget Sound Blood Research Institute | Salsbery B.,Puget Sound Blood Research Institute | Wang M.,Lanzhou University | And 15 more authors.
Blood | Year: 2015

Traumatic brain injury (TBI) is associated with coagulopathy, although it often lacks 2 key risk factors: severe bleeding and significant fluid resuscitation associated with hemorrhagic shock. The pathogenesis of TBI-associated coagulopathy remains poorly understood. We tested the hypothesis that brain-derived microparticles (BDMPs) released from an injured brain induce a hypercoagulable state that rapidly turns into consumptive coagulopathy. Here,wereport that mice subjected to fluid percussion injury (1.9 ± 0.1 atm) developed a BDMP-dependent hypercoagulable state, with peak levels of plasma glial cell and neuronal BDMPs reaching 17 496 ± 4833/μL and 18 388 ± 3657/μL 3 hours after TBI, respectively. Uninjured mice injected with BDMPs developed a dosedependent hyper-turned hypocoagulable state measured by a progressively prolonged clotting time, fibrinogen depletion, and microvascular fibrin deposition in multiple organs. The BDMPs were 50 to 300 nm with intact membranes, expressing neuronal or glial cell markers and procoagulant phosphatidylserine and tissue factor. Their procoagulant activity was greater than platelet microparticles and was dose-dependently blocked by lactadherin. Microparticles were produced from injured hippocampal cells, transmigrated through the disrupted endothelial barrier in a platelet-dependent manner, and activated platelets. These data define a novel mechanism of TBI-associated coagulopathy in mice, identify early predictive markers, and provide alternative therapeutic targets. © 2015 by The American Society of Hematology.

Zhou Z.,National Center for Cardiovascular Diseases | Yu F.,Baylor College of Medicine | Yu F.,Tianjin Medical University | Buchanan A.,University of North Carolina at Chapel Hill | And 8 more authors.
PLoS ONE | Year: 2014

The synthesis, secretion and clearance of von Willebrand factor (VWF) are regulated by genetic variations in coding and promoter regions of the VWF gene. We have previously identified 19 single nucleotide polymorphisms (SNPs), primarily in introns that are associated with VWF antigen levels in subjects of European descent. In this study, we conducted race by gender analyses to compare the association of VWF SNPs with VWF antigen among 10,434 healthy Americans of European (EA) or African (AA) descent from the Atherosclerosis Risk in Communities (ARIC) study. Among 75 SNPs analyzed, 13 and 10 SNPs were associated with VWF antigen levels in EA male and EA female subjects, respectively. However, only one SNP (RS1063857) was significantly associated with VWF antigen in AA females and none was in AA males. Haplotype analysis of the ARIC samples and studying racial diversities in the VWF gene from the 1000 genomes database suggest a greater degree of variations in the VWF gene in AA subjects as compared to EA subjects. Together, these data suggest potential race and gender divergence in regulating VWF expression by genetic variations. © 2014 Zhou et al.

Wang D.,Tianjin Medical University | Wang D.,Key Laboratory of Post Trauma Neuro Repair and Regeneration in Central Nervous System | Wang D.,Tianjin Key Laboratory of Injuries | Wang D.,Tianjin Neurological Institute | And 32 more authors.
Journal of the Neurological Sciences | Year: 2014

Introduction Chronic subdural hematoma (CSDH) is common and more prevalent in the aged population. Surgical intervention is the treatment of choice, but its outcomes may not be satisfactory because of recurrence and physical infirmity associated with aging. Aberrant angiogenesis and localized inflammation contribute to the formation of CSDH. Atorvastatin is active in promoting angiogenesis and modulating inflammation. We hypothesize that atorvastatin is effective in reducing CSDH and have tested the hypothesis in a preliminary prospective study of small cohort of patients. Methods Twenty-three patients with CT- or MRI-confirmed CSDH were recruited from three regional medical centers and evaluated using Markwalder's Grading Scale (MGS) and the Glasgow Coma Scale (GCS). These patients received oral atorvastatin 20 mg/day for 1-6 months (3.02 ± 1.77 months) and were followed for 3 to 36 months (18.62 ± 13.13) after the therapy. Hematoma volume, neurological functions and daily activities (measured using the Activities of Daily Life-the Barthel Index scale, ADL-BI) were compared before and after treatment with Linear Trend Chi-Square test. Results Twenty-two of the 23 patients experienced improvements in symptoms, and the reduction in hematoma volume from 48.70 ± 20.38 ml to 16.64 ± 14.28 ml (paired-sample t-test, p < 0.01) within the first month of the treatment. Hematoma was completely resolved in 17 patients (77.3%) and shrank by more than 73.99% ± 11.17% in 5 patients (22.7%) 3 months after the treatment was initiated. One patient experienced an initial relief of symptoms, but his condition deteriorated with an enlarged hematoma during the 4th week of treatment and underwent surgery. At 6 months, 18 patients presented no hematoma by CT or MRI and four patients, whose hematoma was completely resolved at 3 months, were not followed. None of these 22 patients relapsed during the entire follow-up period of 3-36 months. All have improved MGS, GCS, and ADL-BI. No atorvastatin-related side effects were documented. Conclusion Results of this preliminary prospective study show that the oral administration of atorvastatin is safe and effective in treating CSDH, offering a cost-effective alternative to surgery. A prospective randomized clinical trial is required to validate the effect of atorvastatin. © 2013 Elsevier B.V. All rights reserved.

Li S.,Tianjin Medical University | Li S.,Tianjin Neurological Institute | Li S.,Key Laboratory of Post Trauma Neuro Repair and Regeneration in Central Nervous System | Li S.,Tianjin Key Laboratory of Injuries | And 29 more authors.
Brain Research | Year: 2014

Cerebral aneurysm (CA) rupture is a major cause of subarachnoid hemorrhage with high morbidity and mortality. Using an animal model, we examined the potential of endothelial colony-forming cells (ECFCs) transfusion on vascular degeneration after CA induction and underlying mechanisms. CA was induced in the right anterior cerebral artery-olfactory artery (ACA/OA) bifurcations in Sprague-Dawley rats with or without ECFCs transfusion. The degeneration of internal elastic lamina (IEL), media thickness and CA size were evaluated. Expression of matrix metalloproteinase-2 and 9 (MMP-2 and 9), tissue inhibitor of metalloproteinase-1 (TIMP-1), macrophage chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), nuclear factor κB (NF-κB), endothelial nitric oxide synthase (eNOS), B-cell leukemia/lymphoma-2 (Bcl-2), and inducible nitric oxide synthase (iNOS) were analyzed by quantitative real-time polymerase chain reaction. The macrophages infiltration and apoptosis of smooth muscle cells (SMCs) were examined immunohistologically. Rats in CA+ECFCs transfusion group showed a notable reduction in IEL degeneration, media thinning and CA size compared with those in CA+saline group. ECFCs transfusion inhibited the MMP-driven wall destruction by downregulating MMP-2, MMP-9 expression and upregulating TIMP-1. ECFCs transfusion dramatically decreased VCAM-1 and NF-κB expression, increased eNOS expression and caused no change in MCP-1 expression, which was accompanied by reduced macrophages infiltration. Moreover, ECFCs transfusion reversed downregulation of Bcl-2 expression and upregulation of iNOS expression, and decreased SMCs apoptosis. Collectively, these findings suggest that ECFCs transfusion confers protection against degeneration of aneurysmal wall by inhibiting inflammatory cascades and SMCs apoptosis. © 2014 Elsevier B.V. All rights reserved.

Li S.,Tianjin Medical University | Wang D.,Tianjin Medical University | Tian Y.,Tianjin Medical University | Wei H.,Tianjin Medical University | And 5 more authors.
Neurochemical Research | Year: 2015

Aneurysmal subarachnoid hemorrhage still has a high mortality and morbidity despite notable advances in surgical approaches to cerebral aneurysm (CA). We examined the role of aspirin in vascular inflammation and degeneration. CA was induced in male Sprague–Dawley rats by ligating left common carotid artery and bilateral posterior renal arteries with or without aspirin treatment. The right anterior cerebral artery/olfactory artery (ACA/OA) bifurcations were stripped and assessed morphologically after Verhoeff’s Van Gieson staining. Blood sample was obtained to examine circulating CD34+ CD133+ endothelial progenitor cells (EPCs), platelet aggregation and platelet counts. Macrophages infiltration in aneurysmal wall was evaluated by immunohistochemistry. Expression of matrix metalloproteinase-2 and 9 (MMP-2 and 9), nuclear factor kappa B (NF-κB), macrophage chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) was examined by RT-PCR. 2 months after CA induction, surgically treated rats manifested aneurysmal degeneration in ACA/OA bifurcations. Aspirin-treated rats exhibited a significant decrease in degradation of internal elastic lamina (IEL), medial layer thinning, CA size and macrophages infiltration with reduced expression of MMP-2 and 9 compared with rats in the CA group. RT-PCR demonstrated that the upregulation of NF-κB, MCP-1 and VCAM-1 after CA induction was reversed by aspirin treatment. Aspirin treatment following CA induction increased circulating EPCs to near control levels and reduced platelet aggregation without changing platelet counts. The evidence suggested that aspirin significantly reduced degeneration of aneurysm walls by inhibiting macrophages-mediated chronic inflammation and mobilizing EPCs. © 2015, Springer Science+Business Media New York.

Discover hidden collaborations