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  • Author or Editor: Rui Zhao x
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Sha Zhao, Zhen Liu, Zihan Yu, Xinran Wu, Rui Li and Xiaobo Tang

OBJECTIVE

Inflammation plays a key role in secondary brain damage following intracerebral hemorrhage (ICH). Glycogen synthase kinase–3β (GSK-3β) plays a strong proinflammatory role in many CNS diseases, including stroke. The present study was undertaken to examine the effects of 6-bromoindirubin-3ʹ-oxime (BIO), a specific inhibitor of GSK-3β, on inflammation in ICH rats.

METHODS

An ICH rat model was induced by autologous whole-blood injection into the striatum. First, 10, 20, 40, 60, 80, or 100 μg/kg BIO was applied to ICH animals to determine an optimal dosage for producing sufficient GSK-3β inhibition in rat ipsilateral hippocampus by Western blotting. Second, 40 μg/kg BIO was applied to ICH rats for 1, 3, 7, or 14 days, respectively, to determine a suitable intervention time course of BIO by Western blotting analysis on GSK-3β. Third, Western blotting and enzyme-linked immunosorbent assay were used for quantification of inflammation-related factors upstream or downstream of GSK-3β in rat ipsilateral hippocampus. Then, immunohistochemical staining was applied to detect activated microglia and apoptotic cells in rat ipsilateral hippocampus. Last, neurobehavioral tests were performed to assess the sensorimotor impairments in the ICH rats.

RESULTS

The results show that BIO 1) blocked GSK-3βTyr216 phosphorylation/activation, thus stabilizing β-catenin, increasing upstream brain-derived neurotrophic factor and downstream heat shock protein 70 levels, and decreasing the levels of nuclear factor–κB p65 and cyclooxygenase 2; 2) decreased the levels of the proinflammatory cytokines tumor necrosis factor–α and interleukin (IL)–1β and IL-6 and elevated the level of antiinflammatory cytokine IL-10; 3) inhibited microglia activation and cell apoptosis; and 4) improved the sensorimotor deficits of ICH rats.

CONCLUSIONS

BIO posttreatment inhibited microglia activation, prevented inflammation and hippocampal cell death, and ameliorated functional and morphological outcomes in a rat ICH model through inactivation of GSK-3β.

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Ganjun Feng, Xianfeng Zhao, Hao Liu, Huina Zhang, Xiangjun Chen, Rui Shi, Xi Liu, Xiaodan Zhao, Wenli Zhang and Beiyu Wang

Object

The aim of this study was to compare transplanted mesenchymal stem cells (MSCs) with nucleus pulposus cells (NPCs) in a degenerative disc model in rabbits to determine the better candidate for disc cell therapy.

Methods

Mesenchymal stem cells and NPCs were transplanted in a rabbit model of disc degeneration. Changes in disc height, according to plain radiography, T2-weighted signal intensity on MR imaging, histology, sulfated glycosaminoglycan (sGAG)/DNA, and associated gene expression levels, were evaluated among healthy controls without surgery, sham-operated animals in which only disc degeneration was induced, MSC-transplanted animals, and NPC-transplanted animals for a 16-week period.

Results

Sixteen weeks after cell transplantation, in the MSC- and NPC-transplanted groups, the decline in the disc height index was reduced and T2-weighted signal intensity increased compared with the sham-operated group. Safranin O staining showed a high GAG content, which was also supported by sGAG/DNA assessment. Disc regeneration was also confirmed at the gene expression level using real-time polymerase chain reaction. However, no significant differences in expression were found between the NPC- and MSC-transplanted groups.

Conclusions

Study data showed that MSC transplantation is effective for the treatment of disc degeneration and seems to be an ideal substitute for NPCs.

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Qiao Zuo, Pengfei Yang, Nan Lv, Qinghai Huang, Yu Zhou, Xiaoxi Zhang, Guoli Duan, Yina Wu, Yi Xu, Bo Hong, Rui Zhao, Qiang Li, Yibin Fang, Kaijun Zhao, Dongwei Dai and Jianmin Liu

OBJECTIVE

The authors compared the contemporary perioperative procedure-related complications between coiling with stent placement and coiling without stent placement for acutely ruptured aneurysms treated in a single center after improvement of interventional skills and strategy.

METHODS

In an institutional review board–approved protocol, 133 patients who underwent coiling with stent placement and 289 patients who underwent coiling without stent placement from January 2012 to December 2014 were consecutively reviewed retrospectively. Baseline characteristics, procedure-related complications and mortality rate, angiographic follow-up results, and clinical outcomes were compared between the two groups. Univariate analysis and logistic regression analysis were performed to determine the association of procedure-related complications of coiling with stent placement with potential risk factors.

RESULTS

The coiling/stent group and coiling/no-stent group were statistically comparable with respect to all baseline characteristics except for aneurysm location (p < 0.001) and parent artery configuration (p = 0.024). The immediate embolization results and clinical outcomes between the two groups showed no significant differences (p = 0.807 and p = 0.611, respectively). The angiographic follow-up results of the coiling in stent group showed a significant higher occlusion rate and lower recurrence rate compared with the coiling/no-stent group (82.5% vs 66.7%, 3.5% vs 14.5%, p = 0.007). Procedure-related intraoperative rupture and thrombosis, postoperative early rebleeding and thrombosis, and external ventricular drainage–related hemorrhagic event occurred in 3.0% (4 of 133), 2.3% (3 of 133), 1.5% (2 of 133), 0.7% (1 of 133), and 0.8% (1 of 133) of the coiling/stent group compared with 1.0% (3 of 289), 1.4% (4 of 289), 1.4% (4 of 289), and 0.7% (2 of 289) of the coiling/no-stent group, respectively (p = 0.288, p = 0.810, p = 1.000, p = 0.315, and p = 1.000, respectively). One patient presented with coil protrusion in the group of coiling without stent. The procedure-related mortality was 1.5% (2 of 133) in the coiling/stent group and 0.7% in the coiling/no-stent group (p = 0.796). Multivariable analysis showed no significant predictors for the total perioperative procedure-related complications, hemorrhagic complications, or ischemic complications.

CONCLUSIONS

The perioperative procedure-related complications and mortality rate did not differ significantly between the coiling/stent group and the coiling/no-stent group for patients with acutely ruptured aneurysms. Considering the better angiographic follow-up results, coiling with stent placement might be a feasible, safe, and promising option for treatment in the acute phase of selected wide-necked ruptured intracranial aneurysms.