Morphological and Compositional Features of Chronic Internal Carotid Artery Occlusion in MR Vessel Wall Imaging Predict Successful Endovascular Recanalization.

Background: We sought to determine if the morphological and compositional features of chronic internal carotid artery occlusion (CICAO), as assessed by MR vessel wall imaging (MR-VWI), initially predict successful endovascular recanalization. Methods: Consecutive patients with CICAO scheduled for endovascular recanalization were recruited. MR-VWI was performed within 1 week prior to surgery for evaluating the following features: proximal stump morphology, extent of occlusion, occlusion with collapse, arterial tortuosity, the presence of hyperintense signals (HIS) and calcification in the occluded C1 segment. Multivariate logistic regression was used to identify features associated with technical success and construct a prediction model. Results: Eighty-three patients were recruited, of which fifty-seven (68.7%) were recanalized successfully. The morphological and compositional characteristics of CICAO were associated with successful recanalization, including occlusions limited to C1 and extensive HIS, as well as the absence of extensive calcification, absence of high tortuosity, and absence of artery collapse. The MR CICAO score that comprised the five predictors showed a high predictive ability (area under the curve: 0.888, p < 0.001). Conclusion: the MR-VWI characteristics of CICAO predicted the technical success of endovascular recanalization and may be leveraged for identifying patients with a high probability of successful recanalization.

Stent-assisted coiling of acutely ruptured cerebral aneurysm: a multicenter prospective registry study (SAVE).

BACKGROUND: Stent-assisted coiling (SAC) has been reported as a feasible and effective treatment of wide-neck cerebral aneurysms. However, the evidence of SAC of ruptured cerebral aneurysm is lacking. There are no prospective multicenter studies regarding SAC of acutely ruptured aneurysms within 72 hours after subarachnoid hemorrhage. The purpose of the study is to evaluate the safety and efficiency of SAC of acutely ruptured cerebral aneurysms. METHODS: This study is a prospective, multicenter, and observation registry of consecutive patients with acutely ruptured cerebral aneurysms treated with SAC. Acutely ruptured aneurysms were confirmed within 72 h after the onset of the syndrome. This study will enroll at least 300 patients in 7 high-volume tertiary hospitals (more than 150 cerebral aneurysms treated per year). The primary outcomes are treatment-related thromboembolic complications within 30 days of the treatment. The secondary outcomes are any hemorrhagic complications and aneurysm recurrence at 6 months of angiographic follow-up. The clinical outcomes are measured with the Modified Rankin Scale (mRS) at discharge and at the 6 months of follow-up. The favorable outcomes are defined as an mRS of grades 0 and 2. DISCUSSION: We will perform a prospective, multicenter, and observational registry study of consecutive patients with wide-neck acutely ruptured cerebral aneurysms to improve the safety strategy of SAC of acutely ruptured cerebral aneurysms. TRIAL REGISTRATION: Chinese Clinic Trial Registry: ChiCTR2000036972 ; Registration date: Aug 26, 2020.

Rupture Risk Assessment for Anterior Communicating Artery Aneurysms Using Decision Tree Modeling.

Background: Although anterior communicating artery (ACoA) aneurysms have a higher risk of rupture than aneurysms in other locations, whether to treat unruptured ACoA aneurysms incidentally found is a dilemma because of treatment-related complications. Machine learning models have been widely used in the prediction of clinical medicine. In this study, we aimed to develop an easy-to-use decision tree model to assess the rupture risk of ACoA aneurysms. Methods: This is a retrospective analysis of rupture risk for patients with ACoA aneurysms from two medical centers. Morphologic parameters of these aneurysms were measured and evaluated. Univariate analysis and multivariate logistic regression analysis were performed to investigate the risk factors of aneurysm rupture. A decision tree model was developed to assess the rupture risk of ACoA aneurysms based on significant risk factors. Results: In this study, 285 patients were included, among which 67 had unruptured aneurysms and 218 had ruptured aneurysms. Aneurysm irregularity and vessel angle were independent predictors of rupture of ACoA aneurysms. There were five features, including size ratio, aneurysm irregularity, flow angle, vessel angle, and aneurysm size, selected for decision tree modeling. The model provided a visual representation of a decision tree and achieved a good prediction performance with an area under the receiver operating characteristic curve of 0.864 in the training dataset and 0.787 in the test dataset. Conclusion: The decision tree model is a simple tool to assess the rupture risk of ACoA aneurysms and may be considered for treatment decision-making of unruptured intracranial aneurysms.

Irregular Pulsation of Intracranial Aneurysm Detected by Four-Dimensional CT Angiography and Associated With Small Aneurysm Rupture: A Single-Center Prospective Analysis.

Objectives: Predicting the risk of rupture of small intracranial aneurysms remains challenging. The irregular pulsation of aneurysms detected by four-dimensional CT angiography (4D-CTA) could be an imaging marker of aneurysm vulnerability. We aimed to investigate the association of irregular pulsation with small aneurysm rupture. Materials and Methods: This was a prospective study on intracranial aneurysms detected by 4D-CTA from October 2017 to January 2020. A total of 242 consecutive patients with 316 aneurysms were enrolled. Irregular pulsation was defined as a temporary focal protuberance on more than 3 consecutive frames of the 20 phases in the RR interval. Small aneurysms were defined as those <7 mm. Univariate and multivariate analyses were performed to determine the independent predictors of small aneurysm rupture. Results: A total of 169 patients with 217 small intracranial aneurysms were included. Fourteen (6.5%) of the aneurysms had ruptured, and 77 (35.5%) had irregular pulsation. There were no significant differences in age, sex, hypertension, smoking, diabetes, drinking, or hyperlipidemia between the ruptured and unruptured aneurysm groups. The univariate analysis showed that smaller vessel size (p = 0.008), larger size ratio (p = 0.003), larger aspect ratio (p = 0.006), larger flow angle (p = 0.001), large vessel angle (p = 0.004), middle cerebral artery aneurysms (p = 0.046), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysm (p = 0.006), irregular aneurysm (p = 0.001), and t presence of irregular pulsation (p = 0.001) were associated with small aneurysm rupture. The multivariate analysis showed that the presence of irregular pulsation (p = 0.003), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysms (p = 0.014), and larger flow angle (p = 0.006) was independently associated with aneurysm rupture. Multivariate analysis of predictors of the irregular pulsation of small aneurysms showed that the aneurysm rupture (p = 0.022), irregular aneurysm (p < 0.001), and large size ratio (p = 0.005) were independently associated with the presence of irregular pulsation. Conclusions: The ruptured small aneurysms more often had irregular pulsation. The irregular pulsation was independently associated with aneurysm rupture and may help evaluate the risk of rupture of small intracranial aneurysms.

MiR-429 Inhibits the Angiogenesis of Human Brain Microvascular Endothelial Cells through SNAI2-Mediated GSK-3ß/ß-Catenin Pathway.

MicroRNA (miRNA) dysfunction has been confirmed as a key event of ischemic stroke appearance. This study is aimed at revealing the role of miR-429 in the angiogenesis of HBMECs. The HBMECs were treated with oxygen and glucose deprivation (OGD) to establish the ischemic cell model. The qRT-PCR was used to measure the expression levels of the miR-429 in the serums of the patients or cells, and CCK-8, wound healing assay, and tube formation assay were used to observe the effects of miR-429 on the phenotype of HBMECs. Moreover, the Targetscan, dual-luciferase reporter assay, and Western blot were used to reveal the downstream target and regulation mechanism of miR-429 in OGD-induced HBMECs. The results showed that miR-429 was significantly upregulated in the serums of the patients, and overexpressed miR-429 could extremely inhibit the viability, migration, and tube formation of OGD-induced HBMECs. Furthermore, it was found that SNAI2 was a downstream factor of miR-429, and SNAI2 could rescue the effects of miR-429 on OGD-induced HBMECs. Besides, the Western blot showed that miR-429 could affect the activity of GSK-3ß/ß-catenin pathway via inhibiting the expression of SNAI2. In conclusion, this study suggests that miR-429 inhibits the angiogenesis of HBMECs through SNAI2-mediated GSK-3ß/ß-catenin pathway.

Aneurysm morphological prediction of intracranial aneurysm rupture in elderly patients using four-dimensional CT angiography.

OBJECTIVE: The natural history of unruptured intracranial aneurysms (UIAs) in elderly patients remains poorly understood, and the treatment of UIAs is controversial. The presence of irregular pulsation detected by four-dimensional CT angiography (4D-CTA) is associated with ruptured aneurysms. We aimed to investigate the morphological predictors of irregular pulsation of aneurysms in elderly patients. PATIENTS AND METHODS: We performed a prospective study of intracranial aneurysms detected by 4D-CTA. Elderly patients were defined as those more than 60 years of age. The irregular pulsation was defined as a focal protuberance during a cardiac cycle. We performed multivariate analyses to determine the associations of clinical characteristics and aneurysm morphologies with the irregular pulsation of aneurysms. RESULTS: A total of 128 elderly patients with 166 intracranial aneurysms was included. The irregular pulsation occurred in 71 (42.8%) aneurysms. The multivariate analysis showed that a large size ratio (p = 0.006), posterior circulation aneurysms (p = 0.033), the presence of a daughter dome (p = 0.006), and aneurysm rupture (p = 0.032) were independently associated with the irregular pulsation. The multivariate analysis of predictors of irregular pulsation of unruptured aneurysms showed that size ratio (p = 0.01) and the presence of a daughter dome (p = 0.016) were independent predictors of irregular pulsation. CONCLUSION: A large size ratio, posterior circulation aneurysms, the presence of a daughter dome, and aneurysm rupture were independent predictors of the irregular pulsation of aneurysms in elderly patients. The morphological characteristics detected by 4D-CTA may be helpful to evaluate the risk of rupture of aneurysms.

Apolipoprotein E, low-density lipoprotein receptor, and immune cells control blood-brain barrier penetration by AAV-PHP.eB in mice.

Rationale: The blood-brain barrier (BBB) prevents the effective delivery of therapeutic molecules to the central nervous system (CNS). A recently generated adeno-associated virus (AAV)-based vector, AAV-PHP.eB, has been found to penetrate the BBB more efficiently than other vectors including AAV-PHP.B. However, little is known about the mechanisms. In this study, we investigated how AAV-PHP.eB penetrates the BBB in mice. Methods: We injected AAV-PHP.eB into the bloodstream of wild-type C57BL/6 and BALB/c mice as well as mouse strains carrying genetic mutation in apolipoprotein E gene (Apoe) or low-density lipoprotein receptor gene (Ldlr), or lacking various components of the immune system. Then, we evaluated AAV-PHP.eB transduction to the brain and spinal cord in these mice. Results: We found that the transduction to the CNS of intravenous AAV-PHP.eB was more efficient in C57BL/6 than BALB/c mice, and significantly reduced in Apoe or Ldlr knockout C57BL/6 mice compared to wild-type C57BL/6 mice. Moreover, poor CNS transduction in BALB/c mice was dramatically increased by B-cell or natural killer-cell depletion. Conclusions: Our findings demonstrate that the ApoE-LDLR pathway underlies the CNS tropism of AAV-PHP.eB and that the immune system contributes to the strain specificity of AAV-PHP.eB.

The safety and efficacy of the LVIS stent for the treatment of ruptured intracranial aneurysms within 24 hours: A multicenter retrospective study.

OBJECTIVE: Stent-assisted coiling is increasingly used in the treatment of acutely ruptured intracranial aneurysms. However, the optimal timing of the stent-assisted coiling remains unknown. We aimed to investigate the safety and efficacy of the Low Profile Visualized Intraluminal Support (LVIS) stent for ruptured aneurysms treatment within 24 h comparing to the treatment between 25 and 72 h of symptom onset. PATIENTS AND METHODS: We conducted a multicenter retrospective study on 110 consecutive patients with ruptured intracranial aneurysms. These patients were treated with LVIS stent within 72 h in four tertiary hospitals between January 2017 and December 2017. The timing of treatment was grouped into the treatment within 24 h and the treatment between 25 and 72 h. Baseline characteristics, periprocedural complications, angiographic results, and clinical outcomes were compared between the two groups. RESULTS: A total of 101 patients were included. 49 (48.5 %) patients were treated within 24 h and 52 (51.5 %) within between 25 and 72 h. Periprocedural complications occurred in 2 (4.1 %) patients treated within 24 h compared with those in 10 (19.2 %) treated between 25-72 h (P = 0.032). No early rebleeding occurred in both groups. 45 (91.8 %) of 49 aneurysms had complete occlusion on immediate angiography compared with 46 (88.5 %) of 52 aneurysms had complete occlusion. 2 (2.0 %) aneurysms were retreated. The clinical outcomes and angiographic results did not differ between the two groups. CONCLUSIONS: The LVIS stent-assisted coiling may be safe and effective in the treatment of selected patients with ruptured aneurysms within 24 h of symptom onset.

Morphological risk model assessing anterior communicating artery aneurysm rupture: Development and validation.

OBJECTIVE: Prediction of the rupture risk in anterior communicating artery (ACoA) aneurysms remains challenging. We aimed to investigate the association of detailed morphologies with ACoA aneurysm rupture. PATIENT AND METHODS: 759 consecutive patients with ACoA aneurysms were identified from December 2007 to January 2016. An independent cohort was collected for validation from March 2017 to October 2019. Morphological parameters of the aneurysms were measured using CT angiography. Univariable and multivariable analyses were used to investigate the association of morphological characteristics with aneurysm rupture. Area under receiver operating characteristic curves (AUC) were used to assess the performance of the model. RESULTS: A total of 650 patients with 650 ACoA aneurysms were included for the derivation, and 41 patients with 41 ACoA aneurysms were included for the validation. Aneurysm size, neck size, aspect ratio, size ratio, vessel angle, anterior projection, dominant A1 segment, irregular shape, the presence of a daughter dome, vessel size, and aneurysm angle were risk factors for rupture. The multivariable analysis showed that a larger aneurysm, anterior projection of aneurysms, dominant A1 segment, and irregular aneurysms were associated with aneurysm rupture, whereas larger vessel size was inversely associated with rupture. The morphological risk score showed good discrimination of ruptured and unruptured aneurysms with an AUC of 0.73 in the derivation and an AUC of 0.80 in the validation, and good calibration in both cohorts, signifying a good fit. CONCLUSION: The morphological risk model may contribute to evaluating the risk of rupture of ACoA aneurysms.

MEL Ameliorates Post-SAH Cerebral Vasospasm by Affecting the Expression of eNOS and HIF1α via H19/miR-138/eNOS/NO and H19/miR-675/HIF1α.

Melatonin (MEL) has been demonstrated to exert a protective effect against subarachnoid hemorrhage (SAH), and nitric oxide (NO) has been shown to play an important role in the pathogenesis of vasospasm. This study aims to explore the underlying molecular mechanisms of MEL in the control of vasospasm following SAH. MEL administration attenuates SAH-induced vasospasm and neurobehavioral deficits. Expressions of H19, eNOS, and miR-675 are low in the SAH group, while expressions of miR-138 and HIF1α are high in the SAH group. Also, MEL treatment upon SAH rats completely restores the dysregulation of H19, eNOS, miR-675, miR-138, and HIF1α to their normal levels. Moreover, MEL dose dependently increases the luciferase activity of H19 promoter and hence the expression of H19. Additionally, H19 directly targets miR-675 and miR-138 to increase miR-675 expression and inhibit miR-138 expression. As virtual target genes of miR-675 and miR-138, respectively, HIF1α and eNOS are also regulated by the treatment with MEL. In particular, MEL treatment increases the expression of miR-675 and eNOS level while decreasing the expression of miR-138 and HIF1α in a dose dependent manner. Our study found that MEL ameliorates post-SAH vasospasm by regulating the expression of eNOS and HIF1α via the H19/miR-138/eNOS/NO and H19/miR-675/HIF1α signaling pathways.

Measurement of cerebrovascular reserve by multimodal imaging for cerebral arterial occlusion or stenosis patients: protocol of a prospective, randomized, controlled clinical study.

BACKGROUND: Cerebrovascular reactivity (CVR) is the change in cerebral blood flow in response to a vaso-active stimulus, and may assist the treatment strategy of ischemic stroke. However, previous studies reported that a therapeutic strategy for stroke mainly depends on the degree of vascular stenosis with steady-state vascular parameters (e.g., cerebral blood flow and CVR). Hence, measurement of CVR by multimodal imaging techniques may improve the treatment of ischemic stroke. METHODS/DESIGN: This is a prospective, randomized, controlled clinical trial that aimed to examine the capability of multimodal imaging techniques for the evaluation of CVR to improve treatment of patients with ischemic stroke. A total of 66 eligible patients will be recruited from Renji Hospital, Shanghai Jiaotong University School of Medicine. The patients will be categorized based on CVR into two subgroups as follows: CVR > 10% group and CVR < 10% group. The patients will be randomly assigned to medical management, percutaneous transluminal angioplasty and stenting, and intracranial and extra-cranial bypass groups in a 1:1:1 ratio. The primary endpoint is all adverse events and ipsilateral stroke recurrence at 6, 12, and 24 months after management. The secondary outcomes include the CVR, the National Institute of Health stroke scale and the Modified Rankin Scale at 6, 12, and 24 months. DISCUSSION: Measurement of cerebrovascular reserve by multimodal image is recommended by most recent studies to guide the treatment of ischemic stroke, and thus its efficacy and evaluation accuracy need to be established in randomized controlled settings. This prospective, parallel, randomized, controlled registry study, together with other ongoing studies, should present more evidence for optimal individualized accurate treatment of ischemic stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-16009635; Registered on 16 October 2016. All items are from the World Health Organization Trial Registration Data Set and registration in the Chinese Clinical Trial Registry: ChiCTR-IOR-16009635.

Endovascular Coiling versus Surgical Clipping of Very Small Ruptured Anterior Communicating Artery Aneurysms.

BACKGROUND: Endovascular coiling of anterior communicating artery (ACoA) aneurysms has evolved dramatically. Ruptured ACoA aneurysms are more likely to be smaller. We aimed to investigate the safety and efficacy of endovascular coiling of very small ruptured ACoA aneurysms compared with surgical clipping. METHODS: We conducted a retrospective analysis of consecutive 111 patients with very small ruptured ACoA aneurysms treated with endovascular coiling or surgical clipping in our single center. Very small aneurysms were defined as aneurysm maximal size ≤3.0 mm. Patients were grouped into coiling and clipping groups. Baseline characteristics, postoperative complications, and clinical outcomes were compared between the 2 groups. RESULTS: Forty-six patients (41.1%) underwent successfully coiling, and 65 patients (58.0%) underwent surgical clipping, including 2 patients who failed coiling and crossed over to surgical clipping. The mean size of the ruptured ACoA aneurysms was 2.6 ± 0.5 mm (range, 1.0-3.0 mm). Patients with smaller aneurysms (P = 0.028) or A1 segment complete configuration (P = 0.009) more often underwent surgical clipping, and patients with A1 segment symmetric configuration more often underwent coiling (P = 0.011). There were not statistically significant differences in intraoperative rupture, early rebleeding, cerebral infarction, and seizure in patients treated with clipping and coiling. Clinical outcomes were similar between the 2 groups. There was no retreatment in both groups. CONCLUSIONS: Patients with very small ruptured ACoA aneurysms can be safely and effectively treated with endovascular coiling. However, smaller ACoA aneurysms still require surgical clipping. A smaller aneurysm size limits the use of endovascular coiling.

Clinical Study on Complications of Intracranial Ruptured Aneurysm Embolization by Stent-Assisted Coil.

BACKGROUND The aim of this study was to retrospectively analyze the incidence of complications of intracranial complex aneurysms embolization by stent-assisted coils, and to investigate the causes of complications and corresponding treatment methods. MATERIAL AND METHODS A total of 71 patients with subarachnoid hemorrhage (SAH) underwent stent-assisted coil embolization from 2015 to 2018 were enrolled in this study. Among them, 59 cases were single aneurysm, 12 cases were multiple aneurysms (11 cases with 2 aneurysms and 1 case with 3 aneurysms), for a total of 84 aneurysms. All enrolled patients received stent angioplasty except for 1 case. RESULTS There were 62 aneurysms (73.81%) treated with complete tamponade, 21 aneurysms (25.00%) treated with near-total tamponade and 1 aneurysm (1.19%) treated with partial tamponade. All aneurysms were evaluated based on GOS (Glascow outcome scale): 55 cases had GOS of 5 scores, 12 cases had GOS of 4 scores, 3 cases had GOS of 3 scores, and 1 case had GOS of 1 score. There were 67 SAH patients with good prognosis (GOS of 4-5 scores). In our study, the incidence of complications was 12.7%. Three cases experienced acute thrombosis, 2 cases experienced aneurysm rupture during embolization, and 1 case experienced postoperative focal ischemic changes with mild neurological deficits. CONCLUSIONS Stent-assisted coil embolization is safe, effective, and feasible for the treatment of intracranial ruptured aneurysms. Patients had a favorable outcome of as high as 94.4%. However, clinical skills should be improved to reduce the occurrence of complications. Prompt and timely treatment for complications of intracranial ruptured aneurysm is also of great significance.

Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats.

AIMS: Nerve growth factor (NGF) has been reported to prevent neuronal damage and contributes to the functional recovery in animal brain injury models and human ischemic disease as well. We aimed to investigate a potential therapeutic effect of NGF gene treatment in ischemic stroke and to estimate the functional recovery both at the cellular and cognitive levels in an ischemia rat model. METHODS: After microinjection of pseudolentivirus-delivered ß-NGF into an established ischemic stroke model in rats (tMCAO), we estimated neuronal cell apoptosis with TUNEL labeling and neurogenesis by cell proliferation marker Ki67 staining in both ischemic core and penumbra of striatum. Furthermore, we used behavioral functional tests, Morris water maze performance, to evaluate cognitive functional recovery in vivo and propose a potential underlying mechanism. RESULTS: We found that pseudolentivirus-mediated delivery of ß-NGF gene into the brain induced high expression in striatum of the infarct core area after ischemia in rats. The ß-NGF overexpression in the striatal infarction core after ischemia not only improved neuronal survival by reducing cell apoptosis and increasing cell proliferation, but also rescued cognitive functional impairment through upregulation of GAP-43 protein expression in tMCAO rat model of ischemia. CONCLUSION: This study demonstrates a potential ß-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients.

MiR-377 Regulates Inflammation and Angiogenesis in Rats After Cerebral Ischemic Injury.

Ischemic stroke is the leading cause of disabilities worldwide. MicroRNA-377 (miR-377) plays important roles in ischemic injury. The present study focused on the mechanisms of miR-377 in protecting ischemic brain injury in rats. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. Primary rat microglial cells and brain microvascular endothelial cells (BMECs) were exposed to oxygen-glucose deprivation (OGD). The concentrations of cytokines (TNF-α, IL-1ß, IL-6, IFN-γ, TGF-ß, MMP2, COX2, and iNOS) in the culture medium were measured by specific ELISA. Tube formation assay was for the in vitro study of angiogenesis. Luciferase reporter assay was performed to confirm whether VEGF and EGR2 were direct targets of miR-377. The MCAO rats were intracerebroventricular (ICV) injection of miR-377 inhibitor to assess its protective effects in vivo. MiR-377 levels were decreased in the rat brain tissues at 1, 3, and 7 d after MCAO. Both microglia cells and BMECs under OGD showed markedly lower expression levels of miR-377 while higher expression levels of EGR2 and VEGF compared to those under normoxia conditions. Knockdown of miR-377 inhibited microglial activation and the release of pro-inflammatory cytokines after OGD. Suppression of miR-377 promoted the capillary-like tube formation and cell proliferation and migration of BMECs. The anti-inflammation effect of EGR2 and the angiogenesis effect of VEGF were regulated by miR-377 after OGD. Inhibition of miR-377 decreased cerebral infarct volume and suppressed cerebral inflammation but promoted angiogenesis in MCAO rats. Knockdown of miR-377 lessened the ischemic brain injury through promoting angiogenesis and suppressing cerebral inflammation. J. Cell. Biochem. 119: 327-337, 2018. © 2017 Wiley Periodicals, Inc.

Global transcriptomic study of atherosclerosis development in rats.

Atherosclerosis is a chronic disease of the arterial wall and a leading cause of death worldwide. Though the pathophysiology of atherosclerotic lesion formation has been studied, we still lack evidence of the global changes in the artery during atherosclerosis. In this report, we induced atherosclerosis in rats and conducted GeneChip analysis on carotid arteries with or without plaque formation. We found that molecular pathways underlying plaque formation in atherosclerosis were related to immune response, angiogenesis, cell proliferation, apoptosis and hypoxic microenvironments, suggesting that the pathophysiology of atherosclerosis is varied. In addition, we showed that three lncRNAs, GAS5, SNHG6 and Zfas1, were significantly increased in the plaque of atherosclerosis patients compared to normal people. A complex interaction of mRNA and lncRNA was identified in atherosclerosis. Our results provide a global transcriptomic network of atherosclerosis development in rats and possible targets that could lead to new clinical applications in the future.

Improved neurite outgrowth on central nervous system myelin substrate by siRNA-mediated knockdown of Nogo receptor.

PURPOSE: To investigate the in vitro effect of short interfering RNAs (siRNAs) against Nogo receptor (NgR) on neurite outgrowth under an inhibitory substrate of central nervous system (CNS) myelin. METHODS: Three siRNA sequences against NgR were designed and transfected into cerebellar granule cells (CGCs) to screen for the most effcient sequence of NgR siRNA by using reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. NgR siRNA sequence 1 was found the most efficient which was then transfected into the CGCs grown on CNS myelin substrate to observe its disinhibition for neurite outgrowth. RESULTS: Compared with the scrambled control sequence of siRNA, the NgR siRNA sequence 1 significantly decreased NgR mRNA level at 24 h and 48 h (p <0.05), which was recovered by 96 h after transfection. NgR immunoreactivity was also markedly reduced at 24 and 48 h after the transfection of siRNA sequence 1 compared with that before transfection (p<0.05). The NgR immunoreactivity was recovered after 72 h post-transfection. Moreover, the neurite outgrowth on the myelin substrate was greatly improved within 72 h after the transfection with siRNA sequence 1 compared with the scrambled sequence-transfected group or non-transfected group (p<0.05). CONCLUSION: siRNA-mediated knockdown of NgR expression contributes to neurite outgrowth in vitro.

Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat.

Traumatic brain injury (TBI) treatment is a long-term process and requires repeated medicine administration, which, however, can cause high expense, infection, and hemorrhage to patients. To investigate how a long-term expression of nerve growth factor (Ngf) gene affects the injured hippocampus function post-TBI, in this study, a pseudo lentivirus carrying the ß-Ngf fusion gene, with green fluorescence protein (GFP) gene, was constructed to show the gene expression and its ability of protecting cells from oxidative damage in vitro. Then, the pseudo lentivirus-carried ß-Ngf fusion gene was directly injected into the injured brain to evaluate its influence on the injured hippocampus function post-TBI in vivo. We found that the expression of the pseudo lentivirus-delivered ß-Ngf fusion gene lasted more than four-week after the cell transduction and the encoded ß-NGF fusion protein could induce the neuron-like PC12 cell differentiation. Moreover, the hippocampal injection of the pseudo lentivirus-carried ß-Ngf fusion gene sped the injured cognitive function recovery of the rat subjected to TBI. Together, our findings indicate that the long-term expression of the ß-Ngf fusion gene, delivered by the pseudo lentivirus, can promote the neurite outgrowth of the neuron-like cells and protect the cells from the oxidative damage in vitro, and that the direct and single dose hippocampal injection of the pseudo lentivirus-carried ß-Ngf fusion gene is able to rescue the hippocampus function after the TBI in the rat.

Neuroprotective effect of functionalized multi-walled carbon nanotubes on spinal cord injury in rats.

Traumatic injuries to the brain and spinal cord affect a large percentage of the world's population. However, there are currently no effective treatments for these central nervous system (CNS) injuries. In our study, we evaluated the neuroprotective role of functionalized multi-walled carbon nanotubes (MWCNTs) carrying brain derived neurotrophic factor (BNDF), nogo-66 receptor (NgR) and Ras homolog gene family member A (RhoA) in spinal cord injury (SCI). Our results showed that transfection into rat cortical neurons with BDNF-DNA significantly elevated the expression of BDNF both in vitro and in vivo. Meanwhile, transfection with NgR-siRNA and RhoA-siRNA resulted in an obvious down-regulation of NgR and RhoA in neuron cells and in injured spinal cords. In addition, the functionalized MWCNTs carrying BDNF-DNA, NgR-siRNA and RhoA-siRNA exhibited remarkable therapeutic effects on injured spinal cord. Taken together, our study demonstrates that functionalized MWCNTs have a potential therapeutic application on repair and regeneration of the CNS.

Endovascular treatment of the extracranial carotid pseudoaneurysms resulting from stab penetrating injury using overlapping bare stents.

Injury pertaining to the common carotid artery may result in complete or partial arterial transection, pseudoaneurysms, or arteriovenous connections. Endovascular treatment option of the pseudoaneurysm has already been established with favorable success rate and minimal morbidity. Our purpose is to report one 18-year-old male patient having 2 traumatic pseudoaneurysms as a result of penetrating stab injury in the extracranial common carotid. The patient was successfully treated using 2 overlapping bare-metal stents. The 2 common carotid pseudoaneurysms had different degree inflow angles defined as the space between the lines indicating the direction of blood flow from the parent artery and through the aneurysmal neck to the dome. Computed tomography angiography was utilized to follow the evolution of the pseudoaneurysms until total occlusion was demonstrated. The treatment modality used in this report represents an alternative approach of the endovascular treatment for the extracranial carotid pseudoaneurysm.