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Geng Zhou, Ming Su, Yan-Ling Yin, and Ming-Hua Li

OBJECTIVE

The objective of this study was to review the literature on the use of flow-diverting devices (FDDs) to treat intracranial aneurysms (IAs) and to investigate the safety and complications related to FDD treatment for IAs by performing a meta-analysis of published studies.

METHODS

A systematic electronic database search was conducted using the Springer, EBSCO, PubMed, Medline, and Cochrane databases on all accessible articles published up to January 2016, with no restriction on the publication year. Abstracts, full-text manuscripts, and the reference lists of retrieved articles were analyzed. Random-effects meta-analysis was used to pool the complication rates across studies.

RESULTS

Sixty studies were included, which involved retrospectively collected data on 3125 patients. The use of FDDs was associated with an overall complication rate of 17.0% (95% confidence interval [CI] 13.6%–20.5%) and a low mortality rate of 2.8% (95% CI 1.2%–4.4%). The neurological morbidity rate was 4.5% (95% CI 3.2%–5.8%). No significant difference in the complication or mortality rate was observed between 2 commonly used devices (the Pipeline embolization device and the Silk flow-diverter device). A significantly higher overall complication rate was found in the case of ruptured IAs than in unruptured IA (odds ratio 2.3, 95% CI 1.2–4.3).

CONCLUSIONS

The use of FDDs in the treatment of IAs yielded satisfactory results with regard to complications and the mortality rate. The risk of complications should be considered when deciding on treatment with FDDs. Further studies on the mechanism underlying the occurrence of adverse events are required.

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Jian-Hua Zhong, Hua-Jun Zhou, Tao Tang, Han-Jin Cui, A-Li Yang, Qi-Mei Zhang, Jing-Hua Zhou, Qiang Zhang, Xun Gong, Zhao-Hui Zhang, and Zhi-Gang Mei

OBJECTIVE

Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH.

METHODS

ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats’ brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively.

RESULTS

Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH.

CONCLUSIONS

Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.

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Bing Zhou, Ming-Hua Li, Wu Wang, Hao-Wen Xu, Yong-De Cheng, and Jue Wang

Object

The authors conducted a study to evaluate the advantages of a 3D volume-rendering technique (VRT) in follow-up digital subtraction (DS) angiography of coil-embolized intracranial aneurysms.

Methods

One hundred nine patients with 121 intracranial aneurysms underwent endovascular coil embolization and at least 1 follow-up DS angiography session at the authors' institution. Two neuroradiologists independently evaluated the conventional 2D DS angiograms, rotational angiograms, and 3D VRT images obtained at the interventional procedures and DS angiography follow-up. If multiple follow-up sessions were performed, the final follow-up was mainly considered. The authors compared the 3 techniques for their ability to detect aneurysm remnants (including aneurysm neck and sac remnants) and parent artery stenosis based on the angiographic follow-up. The Kruskal-Wallis test was used for group comparisons, and the kappa test was used to measure interobserver agreement. Statistical analyses were performed using commercially available software.

Results

There was a high statistical significance among 2D DS angiography, rotational angiography, and 3D VRT results (X2 = 9.9613, p = 0.0069) when detecting an aneurysm remnant. Further comparisons disclosed a statistical significance between 3D VRT and rotational angiography (X2 = 4.9754, p = 0.0257); a high statistical significance between 3D VRT and 2D DS angiography (X2 = 8.9169, p = 0.0028); and no significant difference between rotational angiography and 2D DS angiography (X2 = 0.5648, p = 0.4523). There was no statistical significance among the 3 techniques when detecting parent artery stenosis (X2 = 2.5164, p = 0.2842). One case, in which parent artery stenosis was diagnosed by 2D DS angiography and rotational angiography, was excluded by 3D VRT following observations of multiple views. The kappa test showed good agreement between the 2 observers.

Conclusions

The 3D VRT is more sensitive in detecting aneurysm remnants than 2D DS angiography and rotational angiography and is helpful for identifying parent artery stenosis. The authors recommend this technique for the angiographic follow-up of patients with coil-embolized aneurysms.

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Zengpanpan Ye, Xiaolin Ai, and Chao You

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Da Liu, Jun Sheng, Hong-hua Wu, Xia Kang, Qing-yun Xie, Yang Luo, Jiang-jun Zhou, and Wei Zheng

OBJECTIVE

The purpose of this study was to compare stability of injectable hollow pedicle screws with different numbers of holes using different volumes of polymethylmethacrylate (PMMA) in severely osteoporotic lumbar vertebrae and analyze the relationship between screw stability and distribution and volume of PMMA.

METHODS

Forty-eight severely osteoporotic cadaveric lumbar vertebrae were randomly divided into 3 groups—groups A, B, and C (16 vertebrae per group). The screws used in group A had 4 holes (2 pairs of holes, with the second hole of each pair placed 180° further along the thread than the first). The screws used in group B had 6 holes (3 pairs of holes, placed with the same 180° difference in position). Unmodified conventional screws were used in group C. Each group was randomly divided into subgroups 0, 1, 2, and 3, with different volumes of PMMA used in each subgroup. Type A and B pedicle screws were directly inserted into the vertebrae in groups A and B, respectively, and then different volumes of PMMA were injected through the screws into the vertebrae in subgroups 0, 1, 2, and 3. The pilot hole was filled with different volumes of PMMA followed by insertion of screws in groups C0, C1, C2, and C3. Distributions of PMMA were evaluated radiographically, and axial pull-out tests were performed to measure the maximum axial pullout strength (Fmax).

RESULTS

Radiographic examination revealed that PMMA surrounded the anterior third of the screws in the vertebral bodies (VBs) in groups A1, A2, and A3; the middle third of screws in the junction area of the vertebral body (VB) and pedicle in groups B1, B2, and B3; and the full length of screws evenly in both VB and pedicle in groups C1, C2, and C3. In addition, in groups A3 and B3, PMMA from each of the screws (left and right) was in contact with PMMA from the other screw and the PMMA was closer to the posterior wall and pedicle than in groups A1, A2, B1, and B2. One instance of PMMA leakage was found (in group B3). Two-way analysis of variance revealed that 2 factors—distribution and volume of PMMA—significantly influenced Fmax (p < 0.05) but that they were not significantly correlated (p = 0.078). The Fmax values in groups in which screws were augmented with PMMA were significantly better than those in groups in which no PMMA was used (p < 0.05).

CONCLUSIONS

PMMA can significantly improve stability of different injectable pedicle screws in severely osteoporotic lumbar vertebrae, and screw stability is significantly correlated with distribution and volume of PMMA. The closer the PMMA is to the pedicle and the greater the quantity of injected PMMA used, the greater the pedicle screw stability is. Injection of 3.0 mL PMMA through screws with 4 holes (2 pair of holes, with the screws in each pair placed on opposite sides of the screw) produces optimal stability in severely osteoporotic lumbar vertebrae.

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Hua Zhong, Zhihong Zhou, Guo-Hua Lv, Jing Li, and Ming-Xiang Zou

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Yi-Da Tsai, Sung-Hua Chiu, Yuan-Hung Lo, Po-Kuang Yeh, Yuan-Wei Lai, Yi-Ling Tsai, and Dueng-Yuan Hueng

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Hua-Jun Zhou, Hai-Nan Zhang, Tao Tang, Jian-Hua Zhong, Yong Qi, Jie-Kun Luo, Yuan Lin, Qi-Dong Yang, and Xing-Qun Li

Object

Spontaneous intracerebral hemorrhage (ICH) is among the most intractable forms of stroke. Angiogenesis, an orchestrated balance between proangiogenic and antiangiogenic factors, is a fundamental process to brain development and repair by new blood vessel formation from preexisting ones and can be induced by ICH. Thrombospondin (TSP)–1 and TSP-2 are naturally occurring antiangiogenic factors. The aim of this study was to observe their expression in rat brains with ICH.

Methods

Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by stereotactic injection of collagenase VII or autologous blood into the right globus pallidus. The expression of TSP-1 and -2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription–polymerase chain reaction analysis.

Results

After the induction of ICH, some TSP1- or TSP2-immunoreactive microvessels resided around the hematoma for ~ 7 days and extended into a clot thereafter. Cerebral endothelial cells expressed the TSPs. The expression of TSP-1 and TSP-2 mRNA peaked at 4 and 14 days after collagenase-induced ICH, respectively.

Conclusions

Findings in this study suggest that ICH can alter the expression of TSP-1 and TSP-2, which may be involved in modulating angiogenesis in brains following ICH.

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Fu-Lin He, Shuai Qiu, Jian-Long Zou, Fan-Bin Gu, Zhi Yao, Zhe-Hui Tu, Yuan-Yuan Wang, Xiao-Lin Liu, Li-Hua Zhou, and Qing-Tang Zhu

OBJECTIVE

Neuropathic pain caused by traumatic neuromas is an extremely intractable clinical problem. Disorderly scar tissue accumulation and irregular and immature axon regeneration around the injury site mainly contribute to traumatic painful neuroma formation. Therefore, successfully preventing traumatic painful neuroma formation requires the effective inhibition of irregular axon regeneration and disorderly accumulation of scar tissue. Considering that chondroitin sulfate proteoglycans (CSPGs) can act on the growth cone and effectively inhibit axon regeneration, the authors designed and manufactured a CSPG-gelatin blocker to regulate the CSPGs’ spatial distribution artificially and applied it in a rat model after sciatic nerve neurectomy to evaluate its effects in preventing traumatic painful neuroma formation.

METHODS

Sixty female Sprague Dawley rats were randomly divided into three groups (positive group: no covering; blank group: covering with gelatin blocker; and CSPG group: covering with the CSPG-gelatin blocker). Pain-related factors were evaluated 2 and 8 weeks postoperatively (n = 30). Neuroma growth, autotomy behavior, and histological features of the neuromas were assessed 8 weeks postoperatively (n = 30).

RESULTS

Eight weeks postoperatively, typical bulb-shaped neuromas did not form in the CSPG group, and autotomy behavior was obviously better in the CSPG group (p < 0.01) than in the other two groups. Also, in the CSPG group the regenerated axons showed a lower density and more regular and improved myelination (p < 0.01). Additionally, the distribution and density of collagenous fibers and the expression of α–smooth muscle actin were significantly lower in the CSPG group than in the positive group (p < 0.01). Regarding pain-related factors, c-fos, substance P, interleukin (IL)–17, and IL-1β levels were significantly lower in the CSPG group than those in the positive and blank groups 2 weeks postoperatively (p < 0.05), while substance P and IL-17 remained lower in the CSPG group 8 weeks postoperatively (p < 0.05).

CONCLUSIONS

The authors found that CSPGs loaded in a gelatin blocker can prevent traumatic neuroma formation and effectively relieve pain symptoms after sciatic nerve neurotomy by blocking irregular axon regeneration and disorderly collagenous fiber accumulation in the proximal nerve stump. These results indicate that covering the proximal nerve stump with CSPGs may be a new and promising strategy to prevent traumatic painful neuroma formation in the clinical setting.

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Qiang Tan, Qianwei Chen, Yin Niu, Zhou Feng, Lin Li, Yihao Tao, Jun Tang, Liming Yang, Jing Guo, Hua Feng, Gang Zhu, and Zhi Chen

OBJECTIVE

Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study.

METHODS

Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor–κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH.

RESULTS

In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH.

CONCLUSIONS

This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.