The role of wall shear stress in the parent artery as an independent variable in the formation status of anterior communicating artery aneurysms.

OBJECTIVES: The study aimed to determine which hemodynamic parameters independently characterize anterior communicating artery (AcomA) aneurysm formation and explore the threshold of wall shear stress (WSS) of the parent artery to better illustrate the correlation between the magnitude of WSS and AcomA aneurysm formation. METHODS: Eighty-one patients with AcomA aneurysms and 118 patients without intracranial aneurysms (control population), as confirmed by digital subtraction angiography (DSA) from January 2014 to May 2017, were included in this cross-sectional study. Three-dimensional-DSA was performed to evaluate the morphologic characteristics of AcomA aneurysms. Local hemodynamic parameters were obtained using transcranial color-coded duplex (TCCD). Multivariate logistic regression and a two-piecewise linear regression model were used to determine which hemodynamic parameters are independent predictors of AcomA aneurysm formation and identify the threshold effect of WSS of the parent artery with respect to AcomA aneurysm formation. RESULTS: Univariate analyses showed that the WSS (p < 0.0001), angle between the A1 and A2 segments of the anterior cerebral artery (ACA) (p < 0.001), hypertension (grade II) (p = 0.007), fasting blood glucose (FBG; > 6.0 mmol/L) (p = 0.005), and dominant A1 (p < 0.001) were the significant parameters. Multivariate analyses showed a significant association between WSS of the parent artery and AcomA aneurysm formation (p = 0.0001). WSS of the parent artery (7.8-12.3 dyne/cm2) had a significant association between WSS and aneurysm formation (HR 2.0, 95% CI 1.3-2.8, p < 0.001). CONCLUSIONS: WSS ranging between 7.8 and 12.3 dyne/cm2 independently characterizes AcomA aneurysm formation. With each additional unit of WSS, there was a one-fold increase in the risk of AcomA aneurysm formation. KEY POINTS: • Multivariate analyses and a two-piecewise linear regression model were used to evaluate the risk factors for AcomA aneurysm formation and the threshold effect of WSS on AcomA aneurysm formation. • WSS ranging between 7.8 and 12.3 dyne/cm 2 was shown to be a reliable hemodynamic parameter in the formation of AcomA aneurysms. The probability of AcomA aneurysm formation increased one-fold for each additional unit of WSS. • An ultrasound-based TCCD technique is a simple and accessible noninvasive method for detecting WSS in vivo; thus, it can be applied as a screening tool for evaluating the probability of aneurysm formation in primary care facilities and community hospitals because of the relatively low resource intensity.

Treatment of unruptured vertebral dissecting aneurysms: internal trapping or stent-assisted coiling.

PURPOSE: Endovascular treatment is an attractive approach for the treatment of unruptured vertebral dissecting aneurysms, and includes internal trapping and stent-assisted coil embolization. However, the optimal therapy remains debatable. We reviewed our experience with both endovascular treatment modalities and compared the safety, efficacy, and short-term outcomes for each approach. MATERIALS AND METHODS: We retrospectively reviewed 65 consecutive patients with unruptured vertebral dissecting aneurysms who underwent endovascular treatment between January 2003 and January 2014. 24 patients underwent endovascular internal trapping (group A) while 41 patients underwent stent-assisted coiling (group B). Thirteen patients underwent single stent with coiling while 28 patients underwent double or three stent-assisted coiling. Short-term outcomes were evaluated using the modified Rankin Scale. RESULTS: A favorable clinical outcome was achieved in 58 of 65 patients. Procedure-related complications included ischemic symptoms (n = 6) and recurrence (n = 4). There was no statistical difference in modified Rankin Scale scoring between groups. Group A patients had more ischemia symptoms compared with group B patients (p = 0.043), Group B patients had higher recurrence rates compared with group A patients, but the difference had no statistical significance (p = 1.00). However, recurrence only occurred in patients who underwent stent-assisted coiling alone (p = 0.046). CONCLUSION: Stent-assisted coiling for unruptured vertebral dissecting aneurysms may maintain artery patency. Multilayer disposition of stents with coils may decrease complications and facilitate aneurysm occlusion. Larger, prospective studies are necessary to determine the long-term outcomes of reconstructive therapy.

Treatment of giant/large internal carotid aneurysms: parent artery occlusion or stent-assisted coiling.

PURPOSE: Treatment of giant/large internal carotid aneurysm is a challenge for neurologists. Previously, parent artery occlusion was the classic therapy; now the stent-assisted coil embolization has become available in recent years, but the optimal therapy is under debate. The goal of the present study was to compare two endovascular treatment modalities in terms of safety, efficacy and short-term outcomes. METHODS: All the patients were divided into two groups: Group A: patients who underwent parent artery occlusion, and Group B: patients who underwent stent-assisted coil embolization. Follow-up outcomes were evaluated using the modified Rankin Scale (mRS). RESULTS: After 12 months of follow-up, the favorable outcome (mRS: 0-2) had no statistical significance in both groups (p = 1.00). Patients in group A had greater ischemia compared with patients in group B, but the difference did not reach statistical significance (p = 0.421). In group B, patients had a higher rate of partial occlusion (p = 0.255) and recurrence (10% vs. 0%; p = 0.586). CONCLUSIONS: Stent-assisted coiling may not be superior to parent artery occlusion in selected patients after short-term follow-up. Parent artery occlusion is a simple, safe and effective treatment for large/giant internal carotid aneurysms.

Comparative efficacy of Glubran and polyvinyl-alcohol particles in the embolization of meningiomas.

PURPOSE: Preoperative embolization of meningiomas decreases intraoperative bleeding and shortens operation time. However, in meningiomas predominantly vascularized by the internal carotid artery (ICA) or vertebral artery (VA) branches, embolization of external carotid artery feeder branches may lead to a hemodynamic increase in blood supply from the ICA or VA, whereas embolization of ICA or VA feeder branches with particle embolic agents may be associated with complications. This study investigated the safety and efficacy of Glubran, a liquid embolic agent, for the embolization of this type of meningioma compared with polyvinyl-alcohol (PVA) particles. MATERIALS AND METHODS: From January 2006 to June 2015, 157 consecutive patients (98 females; mean age = 48.3 years) who suffered from meningiomas and were preoperatively referred for embolization were retrospectively analyzed. Glubran (n = 40) and PVA (n = 55) were used to devascularize tumors. Sixty-two patients were not embolized because of dangerous anastomosis or other tumor characteristics. Intraoperative blood loss, intraoperative time, degree of angiographic devascularization and embolization-related complications were analyzed. RESULTS: The intraoperative blood loss and operative time were significantly lower in the Glubran-embolized versus non-embolized group. Furthermore, Glubran embolization significantly reduced intraoperative blood loss and operative time for meningiomas that received their primary blood supply from the ICA and/or VA compared with PVA embolization. CONCLUSIONS: Preoperative meningioma embolization with Glubran decreases intraoperative blood loss and operative time. Furthermore, embolization with Glubran produces more effective devascularization compared with PVA for meningiomas supplied by the ICA and/or VA. Thus, Glubran may represent a better embolic agent for this meningioma subtype.

Nefiracetam Attenuates Pro-Inflammatory Cytokines and GABA Transporter in Specific Brain Regions of Rats with Post-Ischemic Seizures.

BACKGROUND/AIMS: Prior studies demonstrated that pro-inflammatory cytokines (PICs) including IL-1ß, IL-6 and TNF-α contribute to regulation of epilepsy-associated pathophysiological processes in the specific brain regions, namely the parietal cortex, hippocampus and amygdala. Moreover, GABA transporter type 1 and 3 (GAT-1 and GAT-3) modulating extracellular GABA levels are engaged in the role played by PICs in epileptogenesis. Note that brain ischemic injury also elevates cerebral PICs. Thus, in this report we examined the effects of nefiracetam (NEF), a pyrrolidone derivative, on the levels of IL-1ß, IL-6 and TNF-α, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala using a rat model of post-ischemic nonconvulsive seizure (NCS). METHODS: NCS was evoked by the middle cerebral artery occlusion (MCAO). ELISA and Western Blot analysis were employed to determine the levels of PICs and GAT-1/GAT-3, respectively. RESULTS: MCAO significantly increased IL-1ß, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala as compared with sham control animals (P<0.05 vs. control rats). Also, in these specific brain regions expression of GAT-1 and GAT-3 was amplified; and the levels of GABA were decreased in rats following MCAO (P<0.05 vs. control rats). Systemic administration of NEF significantly attenuated the elevated PICs, amplified GAT-1 and GAT-3 as well as impaired GABA. NEF also attenuated the number of NCS events following MCAO. CONCLUSION: our data demonstrate that NEF improves post-ischemia evoked-NCS by altering PICs, GABA transporters thereby alleviating GABA in the parietal cortex, hippocampus and amygdala. This support a role for PICs and GABA in engagement of the adaptive responses associated with epileptic activity, but also suggests that NEF has anti-epileptic effects via PICs-GABA mechanisms, having pharmacological implications to target the specific PICs for neuronal dysfunction and vulnerability related to post-ischemic seizures and cognitive impairment.

Predictors of Favorable Outcome of Intracranial Basilar Dissecting Aneurysm.

BACKGROUND: Management of intracranial basilar dissecting aneurysms has been controversial and challenging, and surgical and conservative treatments usually have a bad prognosis. Our study aimed at evaluating the outcomes of endovascular treatment for these lesions and exploring the predictors of favorable outcome. METHODS: We retrospectively reviewed 50 consecutive patients with basilar dissecting aneurysms from January 2006 to January 2013. Twenty-four patients underwent stent-assisted coiling whereas 26 patients underwent conservative treatment. Follow-up outcomes were evaluated using modified Rankin Scale (mRS) score. RESULTS: Of the patients treated with stent-assisted coiling, 20 patients had a favorable outcome (mRS score, 0-1), post-treatment recurrence occurred in 3 patients, 1 had rebleeding, and 2 had no rebleeding. Of the patients treated with conservative therapy (observation or anticoagulation), 10 patients had an unfavorable outcome, 2 patients with ruptured aneurysms developed rebleeding, and 8 patients had poor outcome because of infarct progression. Stent-assisted coiling group had a more favorable outcome than the conservatively treated group (83.3% versus 55.2%, P = .019). Initial complete obliteration was related to the favorable outcome in endovascular-treated group (P = .042). Stent placement was the only independent predictor of favorable outcome in the logistic regression analysis (P = .030; odds ratio = 5.828; 95% confidence interval, 1.192-28.503). CONCLUSIONS: Patients with basilar artery dissecting aneurysms treated with stent-assisted coiling had a more favorable outcome than the conservatively treated patients. Stent placement and initial complete occlusion were the favorable factors in patients with basilar dissecting aneurysm.

Endovascular Treatment of Dissecting Aneurysms of the Posterior Inferior Cerebellar Artery and Predictors of Outcome.

BACKGROUND: Isolated dissecting aneurysms of the posterior inferior cerebellar artery (PICA) are rare lesions, which carry high risk of rebleeding and mortality. However, the existing literature concerning predictors of outcome after endovascular treatment is limited and controversial. Our present study retrospectively reviewed and analyzed the clinical outcome of endovascular treatment-ruptured PICA-dissecting aneurysms and explored the predictors of outcome. METHODS: We retrospectively reviewed 17 consecutive patients with ruptured PICA dissecting aneurysms that underwent endovascular treatment from January 2003 to January 2014. Nine patients underwent selective coiling, whereas 7 patients underwent parent artery occlusion and 1 patient underwent stent-assisted coiling. Follow-up outcomes were evaluated using the modified Rankin Scale. The clinical outcomes of patients were categorized as favorable (modified Rankin Scale [mRS] score 0-1) or unfavorable (mRS score 2-6). RESULTS: Favorable outcomes (mRS score 0-1) were obtained in 13 of 17 patients. Post-treatment recurrence occurred in 1 patient with selective coiling in the 15-month follow-up, and the patient received stent-assisted coiling. The only patients with stent-assisted coiling developed PICA occlusion during follow-up. Aneurysm located in distal segment usually presented with intraventricular hemorrhage (P = .015). Hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks) were associated with unfavorable outcome. CONCLUSIONS: Endovascular treatment of isolated dissecting aneurysm of PICA had excellent clinical outcomes, hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks), which were associated with unfavorable outcome. Long-term follow-ups are necessary to provide stronger conclusions.

Clinical features and endovascular treatment of intracranial arteriovenous malformations in pediatric patients.

PURPOSE: The purpose of this study was to characterize clinical features and evaluate the clinical outcome of endovascular embolization treatment intracranial arteriovenous malformations in pediatric patients. METHODS: A cohort of children (age ≤ 18 years) with arteriovenous malformations (AVMs) from 2000 to 2012 was included. Predictors studied included patient gender, age, and angioarchitectural features, including AVM location, nidus morphology and size, venous drainage, and associated aneurysms. Treatment method, complications and outcomes were recorded. The features of AVMs were evaluated before the treatment. RESULTS: One hundred twenty-seven children (77 males, mean age 13.2 years) were included; 90/127 (70.9 %) children were presented with hemorrhage. AVM size and deep venous drainage were independently associated with hemorrhage; 66/127 patients (52 %) treated with endovascular embolization. Complete obliteration at the end of all endovascular procedures was achieved in 14/66 patients (21.2 %), with an average of 78 % (range, 20-100 %) volume reduction. A mean of 2.9 (range, 1-9) feeding pedicles was embolized per patient. Overall, nine complications occurred in a total of 123 procedures (7.3 %). There was no procedure-related death in this study population. There was no significant difference between patients with and without complications in terms of AVM grade, demographic characteristics, or embolization features. CONCLUSIONS: AVM size and deep venous drainage were independently associated with hemorrhage in pediatric patients. Endovascular procedure is feasible and safe for pediatric AVMs, and complete embolization can be achieved in small AVMs, while large AVMs can be adequately reduced in size for additional microsurgery or stereotactic radiosurgery.

The recovery time of traumatic carotid-cavernous fistula-induced oculomotor nerve paresis after endovascular treatment with detachable balloons.

PURPOSE: The recovery time of traumatic carotid-cavernous fistula-induced oculomotor nerve paresis (ONP) after endovascular embolization with detachable balloons has not yet been adequately evaluated. This study was performed to make a deep analysis of the factors, which affect the prognosis of ONP after endovascular treatment of traumatic carotid-cavernous fistula (TCCF). MATERIALS AND METHODS: We retrospectively evaluated the clinical characteristics and the outcome of oculomotor nerve function in a series of 98 consecutive patients with ONP due to traumatic carotid-cavernous fistula which were endovascular treated with detachable balloons. Univariate analysis was applied to test the association between the time of ONP recovery and clinical variables. RESULTS: Ninety-eight consecutive patients (62 males, 36 females, mean age 34.2±12.7years) having presented with ONP underwent endovascular treatment with detachable balloons were enrolled in this study. ONP was complete in 22 (22.4%) patients and partial in 76 (77.6%) patients. Ninety (91.8%) patients were successfully occluded by single-session endovascular embolization. Retreatments by transarterial routes had to be performed in 8 (8.2%) patients because of recurrent fistula having occurred within 4weeks after embolization. ONP was recovered completely in all the patients, among who 4 (4.1%) were treated with occlusion of internal carotid artery. Factors showing significant association with the recovery time of ONP were the location of the fistula (P=0.007), the degree of preoperative ONP (P=0.003), the number of detachable balloon used (P=0.000) and the length of ONP before endovascular treatment (P=0.000). CONCLUSION: Endovascular treatment of traumatic carotid-cavernous fistula-induced ONP with detachable balloons is a safe and effective method. The length of ONP before endovascular treatment, the location of the fistula, the degree of preoperative ONP, the number of detachable balloons used were the statistically significant predictors of the length of ONP complete recovery.

Surgical cannulation of the superior ophthalmic vein for the treatment of previously embolized cavernous sinus dural arteriovenous fistulas: serial studies and angiographic follow-up.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of transorbital puncture for the retreatment of previously embolized cavernous sinus dural arteriovenous fistulas (DAVFs) via a superior ophthalmic vein (SOV) approach. MATERIALS AND METHODS: During a 12-year period, 9 consecutive patients with previously embolized cavernous sinus DAVFs underwent retreatment via the transorbital SOV approach. RESULTS: All of the nine cases of previously embolized cavernous sinus DAVFs were successfully embolized. Clinical follow-ups were conducted in all nine cases at the duration of 17-141 months (61.22 ± 39.13 months). No recanalization occurred during the follow-up period. A subtle ptosis appeared in two patients and disappeared in one of the two cases after a 4-year follow-up. One patient suffered from paroxysmal positional vertigo and bruit for nearly 2 years after the treatment, but the follow-up angiography demonstrated no recurrence. One patient had persistent visual impairment caused by the initial venous stasis retinopathy. One patient with a history of a procedure-related transient decrease in visual acuity had it return to the normal level. The remaining four cases had clear improvement in the ocular symptoms and became completely asymptomatic during the follow-up period. No patient worsened or developed new symptoms. CONCLUSION: The approach of surgical cannulation of the SOV for the retreatment of previously embolized cavernous sinus DAVFs was proved feasible and efficient, especially when the transarterial and transfemoral venous approaches were inaccessible. However, if the SOV is not dilated enough or is located deeply in the orbit, transorbital venous puncture access may not be possible.

Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells.

BACKGROUND AIMS: This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-ß (TGF-ß), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). METHODS: Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-ß, PDGF-BB, BDNF, GDNF and NGF. RESULTS: The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. CONCLUSIONS: The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.

[Investigation on the hosts with natural Paragonimus infection and species identification in Jinhua Prefecture of Zhejiang Province].

OBJECTIVE: To investigate the natural hosts infected with Paragonimus sp. and identify the species of the parasite in selected counties/districts of Jinhua prefecture in Zhejiang Province. METHODS: Three townships/towns were randomly sampled from each of the 9 counties/districts in Jinhua as pilot spots for the survey. Fresh-water snails were collected from the fields for examining cercariae. Crabs were collected and detected for metacercariae by routine technique and the metacercariae were fed to dogs purchased in areas free from paragonimiasis. Fecal materials of dogs and cats around the villages and streams where crabs were found infected were collected for examining eggs. The artificially infected dogs were sacrificed 55 d after infection to receive adult worms. The size of cercariae, metacercariae, eggs and adult worms was measured. After the DNA of the adult worm was extracted, PCR was used to amplify the COI gene and ITS2 gene of the mitochondria from the worms. Homology with relative strains/isolates was analyzed and phylogenetic tree constructed. RESULTS: The survey demonstrated that the snail Semisulcospira libertina and the crab Sinopotamon chekiangense served as the first and second intermediate hosts respectively. Natural infection was found in Wucheng District with an infection rate of 0.2% (2/1,088) in snails and 76.7% (46/60) in crabs in Shafan township, and an infection index (II) of 2.0 in crabs, 0.1% (1/1,683) in snails and 53.0% (46/60) in crabs with an II of 0.9 in Langya town. The infection rate was 0 (0/575) in snails and 30.0% (18/60) in crabs with an II of 0.1 in Baimu township of Wuyi County. Paragonimus eggs were detected in feces of stray cats with a positive rate of 8.3% (1/12) in Shafan and 0.6% (1/17) in Langya. The size and morphology of the cercariae, metacercariae, eggs and adult worms were similar to those of Paragonimus westermani. The sequences of the COI and ITS2 genes were with 390 bp and 363 bp respectively, indicating a homology of 88.2%-98.2% and 86.5%-88.1% to the 11 strains/isolates of P. westermani recorded in the GenBank. The phylogenetic trees revealed that the parasite in Jinhua was in between the Minchin (Minqing, Fujian) strain and the Japanese Mie and Chiba strains. CONCLUSION: Natural paragonimus infection has been detected in snails, The parasite has been identified as P. westermani which is phylogenetically close to those crabs and cats in Jinhua. reported from Fujian Province and from Mie and Chiba of Japan.

Human umbilical vein-derived dopaminergic-like cell transplantation with nerve growth factor ameliorates motor dysfunction in a rat model of Parkinson's disease.

Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.

[Effects of montelukast and BCG-PSN on the expression of STAT5b mRNA and IL-4 mRNA in blood mononuclearcells of rats with asthma].

OBJECTIVE: To study the expression of signal transducer and activator of transcription 5b (STAT5b) mRNA and interleukin-4 (IL-4) mRNA in blood mononuclearcells in a rat model of asthma and the effect of montelukast (MK) and BCG-polysaccharide and nucleic acid injection (BCG-PSN) on STAT5b mRNA and IL-4 mRNA expression. METHODS: Fifty-two male Sprague-Dawley rats (weight:140-200 g) were randomly divided into four groups: asthma, MK treated and BCG-PSN-treated and control groups. Rat model of asthma was prepared by ovalbumin (OVA) sensitization. The rats were sacrificed 24 hrs after the last sensitization. Blood eosinophils (EOS) were counted. Plasma contens of IL-4 and interferon-gamma (IFN-gamma) were measured using ELISA. Expression of STAT5b mRNA and IL-4 mRNA in blood mononuclearcells was detected with SYBR GREEN I fluorescent quantitation PCR method. RESULTS: Blood contents of STAT5b mRNA and IL-4 mRNA in the untreated asthma group were significantly higher than those in the other three groups (<0.01). Blood EOS count and plasma IL-4 contents in the untreated asthma group significantly increased, while plasma IFN-gamma contents significantly decreased compared with the other three groups (<0.01). There were no significant differences in the parameters measured among the MK-treated, the BCG-PSNjtreated and the control groups. STAT5b mRNA expression was positively correlated to IL-4 mRNA expression, IL-4 content and EOS count (r=0.730,0.650, 0.664, respectively; <0.01), but negatively correlated to IFN-gamma content (r=-0.798; <0.01). CONCLUSIONS: STAT5b mRNA and IL-4 mRNA were strongly expressed in blood mononuclearcells in rats with asthma, and there was a positive correlation between them. MK and BCG-PSN had inhibitory effects on the expression of STAT5b mRNA and IL-4 mRNA, which might be contributed to suppression of airway inflammation in asthma.

A novel small-molecule activator of Sirtuin-1 induces autophagic cell death/mitophagy as a potential therapeutic strategy in glioblastoma.

Sirtuin-1 (SIRT1), the mammalian ortholog of yeast Sir2p, is well known to be a highly conserved NAD+-dependent protein deacetylase that has been emerging as a key cancer target. Autophagy, an evolutionarily conserved, multi-step lysosomal degradation process, has been implicated in cancer. Accumulating evidence has recently revealed that SIRT1 may act as a tumor suppressor in several types of cancer, and thus activating SIRT1 would represent a possible therapeutic strategy. Thus, in our study, we identified that SIRT1 was a key prognostic factor in brain cancer based upon The Cancer Genome Atlas and tissue microarray analyses. Subsequently, we screened a series of potential small-molecule activators of SIRT1 from Drugbank, and found the best candidate compound F0911-7667 (hereafter, named Comp 5), which showed a good deacetylase activity for SIRT1 rather than other Sirtuins. In addition, we demonstrated that Comp 5-induced autophagic cell death via the AMPK-mTOR-ULK complex in U87MG and T98G cells. Interestingly, Comp 5-induced mitophagy by the SIRT1-PINK1-Parkin pathway. Further iTRAQ-based proteomics analyses revealed that Comp 5 could induce autophagy/mitophagy by downregulating 14-3-3γ, catalase, profilin-1, and HSP90α. Moreover, we showed that Comp 5 had a therapeutic potential on glioblastoma (GBM) and induced autophagy/mitophagy by activating SIRT1 in vivo. Together, these results demonstrate a novel small-molecule activator of SIRT1 that induces autophagic cell death/mitophagy in GBM cells, which would be utilized to exploit this compound as a leading drug for future cancer therapy.

Posterior fossa brain arteriovenous malformations : Clinical features and outcomes of endovascular embolization, adjuvant microsurgery and radiosurgery.

BACKGROUND: Posterior fossa brain arteriovenous malformations (PFbAVM) are relatively rare brain disorders but have a high risk of hemorrhage. Endovascular embolization to reduce the lesion size before treatment may improve the outcome of PFbAVM. The purposes of this study were to identify risk factors associated with hemorrhage in PFbAVM and to assess clinical outcomes in patients receiving initial endovascular embolization. MATERIAL AND METHODS: From 1999 to 2013 a total of 63 patients with PFbAVMs were treated (31 males and 32 females, 14.1 % of all AVM cases). A retrospective examination of patient demographics, clinical presentation, angiographic features, treatment modalities, complications and outcomes was carried out. The re-hemorrhage rate, obliteration rate and modified Rankin scale (MRS) were used as measures of outcome. RESULTS: Of the 63 PFbAVM patients 54 (85.7 %) exhibited hemorrhage and 15 had confirmed aneurysms. The cerebellar location (P = 0.007) and deep venous drainage (P = 0.012) were independent predictors of hemorrhage in multivariate analyses. The mean estimated devascularization was 46.9 % (range 10-100 %) in the 20 patients (31.7 %) treated by endovascular embolization. The 16 patients with residual niduses were further treated by radiosurgery, microsurgery or embolization. Complete obliteration was attained in 12 patients (67 %) while 2 (5.7 %) were left with persisting neurological deficits and 1 had a re-hemorrhage 3 years later (annual rate of 4.6 %). Favorable outcome (MRS ≤ 2) was obtained in the 20 patients receiving initial endovascular embolization (P = 0.039 versus preoperative MRS). CONCLUSION: Cerebellar location and deep venous drainage are predictors of hemorrhage in PFbAVM. Adjuvant endovascular embolization is useful and safe for PFbAVM prior to microsurgery or radiosurgery.

High wall shear stress beyond a certain range in the parent artery could predict the risk of anterior communicating artery aneurysm rupture at follow-up.

OBJECTIVE: Among clinical and morphological criteria, hemodynamics is the main predictor of aneurysm growth and rupture. This study aimed to identify which hemodynamic parameter in the parent artery could independently predict the rupture of anterior communicating artery (ACoA) aneurysms by using multivariate logistic regression and two-piecewise linear regression models. An additional objective was to look for a more simplified and convenient alternative to the widely used computational fluid dynamics (CFD) techniques to detect wall shear stress (WSS) as a screening tool for predicting the risk of aneurysm rupture during the follow-up of patients who did not undergo embolization or surgery. METHODS: One hundred sixty-two patients harboring ACoA aneurysms (130 ruptured and 32 unruptured) confirmed by 3D digital subtraction angiography at three centers were selected for this study. Morphological and hemodynamic parameters were evaluated for significance with respect to aneurysm rupture. Local hemodynamic parameters were obtained by MR angiography and transcranial color-coded duplex sonography to calculate WSS magnitude. Multivariate logistic regression and a two-piecewise linear regression analysis were performed to identify which hemodynamic parameter independently characterizes the rupture status of ACoA aneurysms. RESULTS: Univariate analysis showed that WSS (p < 0.001), circumferential wall tension (p = 0.005), age (p < 0.001), the angle between the A1 and A2 segments of the anterior cerebral artery (p < 0.001), size ratio (p = 0.023), aneurysm angle (p < 0.001), irregular shape (p = 0.005), and hypertension (grade II) (p = 0.006) were significant parameters. Multivariate analyses showed significant association between WSS in the parent artery and ACoA aneurysm rupture (p = 0.0001). WSS magnitude, evaluated by a two-piecewise linear regression model, was significantly correlated with the rupture of the ACoA aneurysm when the magnitude was higher than 12.3 dyne/cm2 (HR 7.2, 95% CI 1.5-33.6, p = 0.013). CONCLUSIONS: WSS in the parent artery may be one of the reliable hemodynamic parameters characterizing the rupture status of ACoA aneurysms when the WSS magnitude is higher than 12.3 dyne/cm2. Analysis showed that with each additional unit of WSS (even with a 1-unit increase of WSS), there was a 6.2-fold increase in the risk of rupture for ACoA aneurysms.

Cerebral Microbleeds Could Be Independently Associated with Intracranial Aneurysm Rupture: A Cross-Sectional Population-Based Study.

OBJECTIVE: To determine whether the presence of cerebral microbleeds (CMBs) is independently associated with intracranial aneurysm rupture and to identify the time interval of CMB-related intracranial aneurysm rupture. METHODS: This cross-sectional study included 1847 patients with unruptured and ruptured intracranial aneurysms from January 2010 to November 2017. Clinical records and imaging, including T2-weighted gradient-recalled echo sequence magnetic resonance imaging that identified the presence of CMBs preoperatively, were evaluated. Univariate analysis and multivariate logistic regression were done to determine which parameters were independent factors for aneurysm rupture. The time interval of CMB-related intracranial aneurysm rupture was also evaluated. RESULTS: CMBs confirmed by magnetic resonance imaging were present in 142 patients (142/1847; 7.7%). Of 142 patients with CMBs, 56 patients (including 17 ruptured aneurysms) who received endovascular treatment and another 86 consecutive patients who did not receive embolization or surgery for various reasons were followed for 3-49 months. The incidence of CMB-related intracranial aneurysm rupture was 27.9% (24/86) during the follow-up period. The time interval of CMB-related intracranial aneurysm rupture was 3-27 months (median 9.5 months). Multivariate analyses showed CMBs were significantly correlated with intracranial aneurysm rupture (odds ratio = 1.6; 95% confidence interval, 1.1-2.4; P = 0.010). CONCLUSIONS: CMBs were independently associated with intracranial aneurysm rupture. Patients with CMBs have a 60% increased risk of aneurysm rupture compared with patients without CMBs.

Multidisciplinary Care of Unruptured Brain Arteriovenous Malformations to Improve Symptomatic Headache and the Onset, Progression, and Outcomes of Unruptured Brain Arteriovenous Malformations.

BACKGROUND: Symptomatic headaches attributed to unruptured brain arteriovenous malformations (ubAVMs) are very common and affect patients' quality life, but multidisciplinary care of ubAVMs to improve symptomatic headache remains unclear. OBJECTIVE: The objective is to identify the features of symptomatic headaches, and to obtain headache outcomes following multidisciplinary care of ubAVMs, as well as provide background on the natural history of ubAVMs. STUDY DESIGN: The features of symptomatic headaches and headache outcomes were analyzed in a large cohort of cases after multidisciplinary care of ubAVMs. We have also provided information on the natural history of ubAVMs. SETTING: This study was conducted at the Department of Neurosurgery of Zhujiang Hospital where 336 patients from 1998 to 2014 were reviewed by a multidiscipline team. Only 124 patients were eligible. METHODS: The demographics, clinical features, imaging features, and headache details of eligible patients were reviewed. An 11-point pain scale score was used to assess symptomatic headaches before, during, and after treatment. The headache outcomes, death or stroke, and adverse functional outcomes (modified Rankin Scale score = 2, mRS = 2) were assessed following multidisciplinary care of ubAVMs. RESULTS: Twenty-three (56.1%) of 41 patients had migraine-like headaches located in occipital lobe (P < 0.001), while forty (63.5%) of 63 patients had tension-type-like headaches located in frontotemporal lobe (P < 0.001). For patients with tension-type-like or all types of headache, headache improvement differed between the multidisciplinary group and medical group (87.8% vs. 31.8%, P < 0.001; 85.7% vs. 40.7%, P < 0.001). The risk of death or stroke did not differ between multidisciplinary group and medical group (P = 0.393), whereas the risk of adverse functional outcome (mRS = 2) differed significantly by long-time follow-up (23.0% vs.10.0%, P = 0.022). LIMITATIONS: This study provides the initial experience to support multidisciplinary care for ubAVMs to improve symptomatic headaches and patients' quality life, but based on the retrospective study with inherent limitations, larger samples and multi-center trials are needed on this interesting issue. CONCLUSIONS: Occipital ubAVM is more likely to present with migraine-like headache, while frontotemporal ubAVM tends to present with tension-type-like headache. The effectiveness of multidisciplinary care for ubAVM to improve headache has been shown, but the natural history of ubAVM patients with headache remains unclear.Key Words: Unruptured brain arteriovenous malformations, headache, headache improvement, natural history.