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Wang D.,Tianjin Medical University | Li T.,Tianjin Medical University | Wei H.,Tianjin Medical University | Wang Y.,Tianjin Medical University | And 9 more authors.
Journal of the Neurological Sciences

Background and purpose Statins are active in reducing plasma lipids, suppressing inflammation and promoting angiogenesis. Because angiogenesis is critical for the absorbance of subdural hematoma (SDH), we hypothesize that atorvastatin promotes angiogenesis to enhance hematoma absorption. Methods SDH was induced in adult Wistar rats and treated with 3 mg/kg, 8 mg/kg of atorvastatin, or vehicle saline daily for 7 days. The treated rats were examined for the level of CD34 +/CD133 + endothelial progenitor cells (EPCs) in the circulation by flow cytometry, hematoma volumes by magnetic resonance imaging (MRI), and changes in cognitive functions. We also examined angiogenesis in the hematoma wall by transmission electronic microscopy and immunohistochemistry for the expression of vascular endothelial growth factor (VEGF), matrix metalloprotease 9 (MMP 9) and angiopoietin. Results SDH volume was significantly reduced and neurological deficits improved in rats receiving the low dose atorvastatin compared to those receiving either the high dose of atorvastatin or saline. Consistent with these outcome measures, the low dose atorvastatin increased the expression of angiopoient-1 and VEGF and reduced MMP9 expression in the connective tissue of the SDH wall, resulting in an increased vascular density and enhanced vascular maturation. Conclusions The low-dose atorvastatin is effective in reducing SDH and improving neurological deficits in a rat model, primarily by promoting angiogenesis and vascular maturation. © 2016 Published by Elsevier B.V. Source

Wang L.,Tianjin 5th center Hospital | Liu X.-Z.,Tianjin 5th center Hospital | Liu Z.-L.,Tianjin 5th center Hospital | Lan F.-M.,Tianjin 5th center Hospital | And 3 more authors.
Chinese Medical Journal

Background Carotid stenosis is one of the common reasons for patients with ischemic stroke, and the two invasive options carotid endarterectomy (CEA) and carotid artery stenting (CAS) are the most popular treatments. But the relative efficacy and safety of the methods are not clear. Methods About 521 articles related to CAS and CEA for carotid stenosis published in 1995-2011 were retrieved from MEDLINE, Cochrane Library (CL), and China National Knowledge Infrastructure (CNKI) China Journal Full-Test database. Of them, eight articles were chosen. Meta-analysis was used to assess the relative risks. Results The eight studies included 3873 patients with symptomatic carotid artery stenosis, including 1941 cases in the carotid stent angioplasty group, and 1932 cases in the carotid endarterectomy group. Fixed effect model analysis showed that within 30 days of incidence of all types of strokes, surgery was significantly highly preferred in CAS patients (CAS group) than the CEA patients (CEA group), and the difference was statistically significant (relative ratio (RR)=1.80, 95% confidence interval (CI): 1.380-2.401, P <0.0001). But the incidence of death in the two groups is not showed and is not statistically significant after 30 days (RR=1.52, 95% CI: 0.82-2.82, P=0.18). The rate of cranial nerve injury in the CAS group is lower than the CEA group (RR=0.14, 95% CI: 0.05-0.43, P=0.0005). The incidence of CAS patients with myocardial infarction is lower than the CEA group after 30 days, but statistically meaningless (RR=0.22, 95% CI: 0.05-1.02, P=0.05). The stroke or death in CAS patients were higher than the CEA group after 1 year of treatment (RR=2.58, 95% CI: 1.03-6.48, P=0.04). Conclusions Compared to CAS, carotid endarterectomy is still the preferred treatment methodology of symptomatic carotid artery stenosis. Future meta-analyses should then be performed in long-term follow-up to support this treatment recommendation. Source

Wang L.,Tianjin 5th center Hospital | Wang X.,Nankai Hospital | Su H.,University of California at San Francisco | Han Z.,Tianjin Medical University | And 5 more authors.
Translational Stroke Research

Previous studies show that circulating endothelial progenitor cells (EPCs) promote angiogenesis, which is a process associated with improved recovery in animal models of traumatic brain injury (TBI), and that recombinant human erythropoietin (rhEPO) plays a protective role following stroke. Thus, it was hypothesized that rhEPO would enhance recovery following brain injury in a rat model of TBI via an increase in the mobilization of EPCs and, subsequently, in angiogenesis. Flow cytometry assays using CD34- and CD133-specific antibodies were utilized to identify alterations in EPC levels, CD31 and CD34 antibody-stained brain tissue sections were used to quantify angiogenesis, and the Morris water maze (MWM) test and the modified Neurological Severity Score (mNSS) test were used to evaluate behavioral recovery. Compared with saline treatment, treatment with rhEPO significantly increased the number of circulating EPCs on days 1, 4, 7, and 14 (P < 0.05), improved spatial learning ability on days 24 and 25 (P < 0.05), and enhanced memory recovery on day 26 (P < 0.05). Moreover, rhEPO treatment decreased mNSS assessment scores on days 14, 21, and 25 (P < 0.05). There was a strong correlation between levels of circulating EPCs and CD34- and CD31-positive cells within the injured boundary zone (CD34+r = 0.910, P < 0.01; CD31+r = 0.894, P < 0.01) and the ipsilateral hippocampus (CD34+r = 0.841, P < 0.01; CD31+r = 0.835, P < 0.01). The present data demonstrate that rhEPO treatment improved functional outcomes in rats following TBI via an increase in the mobilization of EPCs and in subsequent angiogenesis. © 2014, Springer Science+Business Media New York. Source

Wang L.,Tianjin 5th center Hospital | Shi W.,Tianjin 5th center Hospital | Su Z.,Tianjin 5th center Hospital | Liu X.,Tianjin 5th center Hospital | And 4 more authors.
Journal of Clinical Neuroscience

Severe acute basilar artery occlusion (BAO) has a high mortality rate but as yet no effective treatment has been developed. This study aimed to evaluate the feasibility and safety of combined mechanical thrombectomy, intra-Arterial thrombolysis, and emergent stent placement for patients with severe acute BAO. Eighteen patients who were unconscious after confirmed onset of BAO and who were given arterial interventional treatment from March 2011 to June 2013 at our department were included in this study. The mean age was 59.56 years (range: 31-76 years) and patients were in a critical physical condition upon admission, and had a mean National Institutes of Health Stroke Scale (NIHSS) score of 25.94 (range: 18-35). All patients were treated with mechanical thrombectomy, 10 of whom received mechanical thrombectomy only. Of the others, eight were also treated with intra-Arterial thrombolysis, three were treated with emergent stent placement, and 17 were treated with recanalization with an achieved recanalized rate of 94.4%. The average number of passes through the stent was 1.5 (range: 1-3) and five patients died (27.8%). Thirteen patients survived, and the mean NIHSS score was 6.54 (range: 0-16). Seven patients showed a modified Rankin Scale score ≤2, and the rate of good prognoses was 38.9%. In the treatment of patients with severe acute BAO, intra-Arterial mechanical thrombectomy combined with thrombolysis or stent placement are effective strategies to restore blood flow and preserve life, and these strategies have a low incidence of complications. © 2014 Published by Elsevier Ltd. Source

Li G.,Tianjin 5th center Hospital | Liu X.,Tianjin 5th center Hospital | Liu Z.,Tianjin 5th center Hospital | Su Z.,Tianjin 5th center Hospital
Molecular Medicine Reports

Connexin 43 (Cx43) and aquaporin-4 (AQP4) have important roles in the formation of glioma-induced brain edema; however, the association between these two factors in the development of edema has remained to be elucidated. In the present study, immunofluorescence and western blot analysis revealed that in a rat model of intracranial C6 glioma, Cx43 expression levels were low to undetectable and AQP4 expression levels were low in glioma cells. Significantly higher Cx43 and AQP4 levels were detected in the tissue surrounding the glioma. To further investigate the potential interaction between Cx43 and AQP4, normal glial cells and C6 glioma cells were cultured in hypotonic medium. Reverse transcription quantitative polymerase chain reaction indicated that AQP4 and Cx43 mRNA expression levels increased as a function of time in normal glial cells and C6 glioma cells in a hypotonic environment. However, the increase observed in normal glial cells was significantly lower than that observed in C6 glioma cells. Furthermore, AQP4 expression levels changed prior to alterations in Cx43 expression. Following AQP4 silencing in C6 cells, the increase in Cx43 expression was significantly attenuated (P<0.05). In normal cells, Cx43 silencing did not influence AQP4 expression (P>0.05). Therefore, it was hypothesized that AQP4 and Cx43 had two distinct mechanisms underlying brain edema formation within and surrounding the glioma. Cx43 may be a downstream effector of AQP4. The elucidation of this pathway may aid in the development of drugs targeting the interaction between AQP4 and Cx43, providing novel therapeutic possibilities for glioma-induced brain edema. Source

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