Zhiyuan Yu, Jun Zheng, Rui Guo, Chao You, Hao Li and Lu Ma
Zhiyuan Yu, Rui Guo, Jun Zheng, Hao Li, Chao You and Lu Ma
Guo Yu, Peixi Liu, Yuan Shi, Sichen Li, Yingjun Liu, Zhiyuan Fan and Wei Zhu
Emerging evidence shows that frequent recurrence of intracranial aneurysms (IAs) after endovascular coiling is attributable to the lack of endothelialization across the aneurysm neck. Recently, much attention has been given to the role of microRNAs (miRs) in vascular disease, although their contributory role to IA is poorly understood.
Adult male Sprague-Dawley rats were subjected to microsurgery to create a coiled embolization aneurysm model, and were injected with miR-31a-5p agomir or a negative control agomir via the tail vein at a dose of 10 mg/kg per week for 4 weeks after IA induction. H & E staining, scanning electron microscopy, and flow cytometry were performed to evaluate the effects of miR-31a-5p agomir on endothelialization and the number of circulating endothelial progenitor cells (EPCs). The effects of miR-31a-5p on the viability and functioning of EPCs were also determined using Cell Counting Kit–8, wound-healing assay, and tube formation assays.
The authors tested the ability of miR-31a-5p to promote EPC-induced endothelialization in a model of coiled embolization aneurysm. miR-31a-5p agomir improved endothelialization and elevated the number of circulating EPCs in the peripheral blood compared to a negative control agomir–treated group. In addition, the number of vWF- and KDR-positive cells in the aneurysm neck was increased in the miR-31a-5p agomir–treated group. Furthermore, upregulation of miR-31a-5p promoted EPC proliferation, migration, and tube formation and enhanced the expression of the proangiogenic factor vascular endothelial growth factor in vitro. Mechanistically, miR-31a-5p directly targeted the 3′ untranslated region (3′UTR) of Axin1 messenger RNA and repressed its expression. Besides, miR-31a-5p exerted its effect on EPCs by regulating the Axin1-mediated Wnt/β-catenin pathway.
Collectively, these results indicate that miR-31a-5p is an important regulator of EPC mobilization and endothelialization and may have a positive effect on aneurysm repair.
Xin-Yu Lu, Hui Sun, Jian-Guo Xu and Qiao-Yu Li
Over the last two decades, stereotactic radiosurgery (SRS) has arisen as a promising approach in the management of brainstem cavernous malformations (CMs). In the present study, the authors report a systematic review and meta-analysis of the available published data regarding the radiosurgical management of brainstem CMs.
To identify eligible studies, systematic searches for brainstem CMs treated with SRS were conducted in major scientific publication databases. The search yielded 5 studies, which were included in the meta-analysis. Data from 178 patients with brainstem CMs were extracted. Hemorrhage rates before and after SRS were calculated, a meta-analysis was performed, and the risk ratio (RR) was determined.
Four studies showed a statically significant reduction in the annual hemorrhage rate after SRS. The overall RR was 0.161 (95% CI 0.052–0.493; p = 0.001), and 21 patients (11.8%) had transient or permanent neurological deficits.
The present meta-analysis for the radiosurgical management of brainstem CMs shows that SRS can decrease the rate of repeat hemorrhage and has a low rate of adverse effects compared with surgery. The authors suggest that SRS may be considered as an alternative treatment for brainstem CMs that are inoperable or have a high operative risk.
Guo-jie Hu, Yu-gong Feng, Wen-peng Lu, Huan-ting Li, Hong-wei Xie and Shi-fang Li
Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction.
An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad-VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad-VEGF165-SDF-1 or control adenovirus Ad-LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI.
The Ad-VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion.
Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral infarction.
JianMing Luo, Bin Liu, ZeYu Xie, Shan Ding, ZeRui Zhuang, Lan Lin, YanChun Guo, Hui Chen and Xiaojun Yu
The object of this study was to compare the effects and complications of manual and computer-aided shaping of titanium meshes for repairing large frontotemporoparietal skull defects following traumatic brain injury.
From March 2005 to June 2011, 161 patients with frontotemporoparietal skull defects were observed. Patients were divided into 2 groups according to the repair materials used for cranioplasty: 83 cases used computer-aided shaping for the titanium mesh, whereas the remaining 78 cases used a manually shaped titanium mesh. The advantages and disadvantages of the 2 methods were compared.
No case of titanium mesh loosening occurred in either group. Subcutaneous fluid collection, titanium mesh tilt, and temporal muscle pain were the most common complications. In the manually shaped group, there were 14 cases of effusion, 10 cases of titanium mesh tilt, and 15 cases of temporal muscle pain. In the computer-aided group, there were 6 cases of effusion, 3 cases of titanium mesh tilt, and 6 cases of temporal muscle pain. The differences were significant between the 2 groups (p < 0.05). Other common complications were scalp infection, exposure of titanium mesh, epidural hematoma, and seizures. In the computer-aided group, the operative time decreased (p < 0.01), the number of screws used was reduced (p < 0.01), and the satisfaction of patients was significantly increased (p < 0.05).
Computer-aided shaping of titanium mesh for repairing large frontotemporoparietal skull defects decreases postoperative complications and the operative duration, reduces the number of screws used, increases the satisfaction of patients, and restores the appearance of the patient's head, making it an ideal choice for cranioplasty.
Yu Shuang Tian, Di Zhong, Qing Qing Liu, Xiu Li Zhao, Hong Xue Sun, Jing Jin, Hai Ning Wang and Guo Zhong Li
Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke–related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke.
The JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)–treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)–induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3′ untranslated region (3′UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase–9 [MMP-9], tumor necrosis factor–α [TNF-α], and interleukin-1β [IL-1β]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V–FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits.
JAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3′UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1β). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit.
These findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.
Yu Lei, Yan-Jiang Li, Qi-Hao Guo, Xing-Dang Liu, Zhuang Liu, Wei Ni, Jia-Bin Su, Heng Yang, Han-Qiang Jiang, Bin Xu, Yu-Xiang Gu and Ying Mao
Chronic frontal hemodynamic disturbances are associated with executive dysfunction in adult patients with moyamoya disease (MMD). However, the impact of surgical revascularization on executive dysfunction and its underlying mechanism remains unclear. The aim of the present study was to examine the postoperative radiological correlates of cognitive improvement and thereby explore its underlying mechanism.
Fourteen patients who met the inclusion criteria were identified at Huashan Hospital, were operated on, and were successfully followed up for 6 months. Postoperative changes in cortical perfusion and regional amplitude of low-frequency fluctuations (ALFF) were examined by SPECT and resting-state functional MRI, respectively. Executive function was evaluated by 2 tests (Trail Making Test Part B and the summation of executive subtests of Memory and Executive Screening [MES-EX]). Follow-up neuropsychological outcomes were then correlated with radiological changes to identify nodes functioning as leading contributors to postoperative executive outcomes.
All patients underwent successful unilateral bypass procedures, with some operations performed on the left side and some on the right side. At the 6-month follow-up, the baseline and follow-up test scores for the different sides did not differ significantly. The group with good collaterals (Matsushima Grade A, 9 patients) exhibited significantly increased postoperative perfusion (change in [△] hemodynamics) in bilateral frontal (left, p = 0.009; right, p = 0.003) and left parietal lobe (p = 0.014). The Spearman's correlation test suggested that only the right frontal lobe exhibited significant positive postoperative radiological correlates with cognitive performance (△MES-EX vs △hemodynamics, r = 0.620, p = 0.018; △MES-EX vs △ALFF, r = 0.676, p = 0.008; △hemodynamics vs △ALFF, r = 0.547, p = 0.043). Subsequent regional ALFF analysis revealed that the right dorsolateral prefrontal cortex (DLPFC) was the only node in the responsible hemisphere to exhibit significant postoperative changes.
The results not only advance our understanding of pathological interactions of postoperative executive performance in adult MMD, but also indicate that the right DLPFC amplitude might be a quantitative predictor of postoperative executive control improvement.
Hong-Qi Zhang, Tong Chen, Shao-Shuai Wu, Liang-Hong Teng, Yong-Zhong Li, Li-Yong Sun, Zhi-Ping Zhang, De-Yu Guo, De-Hong Lu and Feng Ling
The authors undertook this study to establish an animal model to investigate the pathophysiological changes of venous hypertensive myelopathy (VHM).
This study was a randomized control animal study with blinded evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by means of renal artery and vein anastomosis and trapping of the posterior vena cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by spinal function evaluation, abdominal aortic angiography, spinal MRI, and pathological examination of the spinal cord at different follow-up stages.
Twenty-two (91.67%) of 24 model rabbits survived the surgery and postoperative period. The patency rate of the arteriovenous fistula was 95.45% in these 22 animals. The model rabbits had significantly decreased motor and sensory hindlimb function as well as abnormalities at the corresponding segments of the spinal cord. Pathological examination showed dilation and hyalinization of the small blood vessels, perivascular and intraparenchymal lymphocyte infiltration, proliferation of glial cells, and neuronal degeneration. Electron microscopic examination showed loose lamellar structure of the myelin sheath, increased numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons.
This model of VHM is stable and repeatable. Exploration of the sequential changes in spinal cord and blood vessels has provided improved understanding of this pathology, and the model may have potential for improving therapeutic results.