LncRNAGAS5 sponges miRNA-221 to promote neurons apoptosis by up-regulated PUMA under hypoxia condition.

Objectives: Long noncoding RNAs (lncRNAs) play substantial roles in cerebral ischemia. Growth arrest-specific 5 (GAS5) was reported to be involved in stroke. In the present study, we aimed to investigate the roles of GAS5 in cerebral condition and unveil the underlying mechanism.Method: Transient focal ischemia was induced by intraluminal occlusion of the right Middle cerebral artery occlusion (MCAO) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the volume of cerebral infarction. RT-qPCR was applied to evaluate the level of GAS5 and miR-221. Fluorescence activated Cell Sorting (FACS) and Terminal deoxynucleotidyl transferased (TUNEL)  were used for detection of apoptosis. Western blotting was applied for protein level. Luciferase assay was applied to reveal the underlying relationship between GAS5 and miR-221 or p53-upregulated modulator of apoptosis (PUMA) and miR-221.Results: The results indicated that GAS5 was up-regulated in MCAO rats and in vitro hypoxia cell model while miR-221 expression was decreased in vitro hypoxia cell model. GAS5 promoted cells apoptosis, while miR-221 inhibited cell apoptosis through regulation of PUMA and downstream JNK/H2AX signaling. Moreover, GAS5 and miR-221 have direct interaction and PUMA was the target of miR-221, indicating that GAS5 regulated PUMA through sponging miR-221.Conclusions: the present study revealed that GAS5 aggravated cell apoptosis in hypoxia condition via miR-221/PUMA axis, which may provide potential targets for the treatment of stroke.

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.

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.

Fistula and Infratentorial Location, Characteristics That Contribute to Cerebral Arteriovenous Malformations, Lead to the Formation of Associated Aneurysms in Patients.

OBJECTIVE: Because the formation of associated aneurysms (AAs) related to the characteristics of cerebral artriovenous malformations (cAVMs) is poorly recognized, the purpose of this study was to identify the responsible characteristics of cAVMs related to the formation of AAs and to identify patients with responsible characteristics related to the formation of AAs through the analysis of the outcomes of these patients after treatment. METHODS: This study was performed to analyze the baseline characteristics of patients with cAVMs and AAs. The recurrent AA and residual size of cAVMs were used to evaluate the outcomes of patients after treatment. At the same time, the ROC curve was measured to gauge the relationship between the residual size of cAVMs and recurrent AAs in eligible patients. RESULTS: Fifty (15.0%) patients with cAVMs and AA were confirmed; these patients had twice the hazard of hemorrhage as patients with only isolated cAVMs. An infratentorial location (P < 0.001) and fistula (P = 0.002) were independent predictors of the formation of AAs. After a mean 22.7 months follow-up, 2 patients developed recurrent AAs, and the annual recurrence rate for patients with responsible characteristics was 17.6%, but for all patients was 7.2%. The ROC curve showed that patients, specifically patients with responsible characteristics, the residual size of the cAVM was closely related to recurrent AA (area = 0.89, 95% confidence interval 0.81-0.97, P = 0.023, cut-off value = 82.5%). CONCLUSIONS: Patients with cAVMs and AA who harbor a fistula or an infratentorial location tend to form AAs. To prevent recurrent AAs and decrease the subsequent risk of hemorrhage, complete obliteration of cAVMs or retrograding over 80% size of cAVMs is recommended.

Comparison between Solitaire™ AB and Enterprise stent-assisted coiling for intracranial aneurysms.

The aim of the present study was to analyze the feasibility, rate of procedure-related complications and midterm angiographic follow-up outcomes using the Enterprise (EP) and Solitaire™ AB (ST) stents in the stent-assisted coiling of intracranial aneurysms. In total, 81 patients with 90 aneurysms were included in the study, with the aim to treat 43 aneurysms with the EP stent (47.8%) and 47 aneurysms with the ST stent (52.2%). The 90 aneurysms were successfully stented and subsequently coiled; however, in four patients undergoing treatment with the EP stent, the stent was not navigable; thus, treatment with the ST stent was employed (EP, n=39, 43.3%; ST, n=51, 56.7%). Of the 90 aneurysms, 44 cases were ruptured aneurysms, with 74 located in the anterior circulation and 16 located in the posterior circulation. The stenting success rate of the ST stent was significantly higher compared with the EP stent. However, no statistically significant differences were observed with regard to the packing density, complete occlusion, progressive occlusion, recurrence rate, procedure-related complications, in-stent stenosis and stent migration rates between the two groups. In conclusion, the two common medical devices used for intracranial aneurysms are relatively safe and effective for the treatment of intracranial aneurysms. However, due to the higher stenting success rate of the ST stent, this medical devise was demonstrated to be more flexible and feasible compared with the EP stent.

Influencing factors of immediate angiographic results in intracranial aneurysms patients after endovascular treatment.

The purpose of this study was to analyze influencing factors associated with immediate angiographic results in intracranial aneurysms patients after endovascular treatment (EVT), providing theoretical evidence and guidance for clinical treatment of intracranial aneurysms. Totally 529 patients met the inclusive criteria, consisting of 338 males and 191 females. Gender; age; history of hypertension, diabetes, and smoking; intracranial atherosclerosis; rupture status, size and location, features of aneurysmal neck, shapes; vasospasm; treatment modality; and degree of aneurysm occlusion were all carefully and completely recorded. All data were investigated in univariate and multivariate logistic regression model to determine whether they were correlated with the degree of aneurysm occlusion. According to aneurysm size, aneurysms were classified as micro-miniature, miniature, and large aneurysms. There were 451 narrow-neck aneurysms and 78 wide-neck aneurysms. Totally 417 were regular and 112 were irregular. And 125 were un-ruptured aneurysms; 404 were ruptured aneurysms. The modalities of treatment were as follows: embolization with coil (n = 415), stent-assisted coil embolization (n = 89), and balloon-assisted coil embolization (n = 25). Univariate analysis showed that aneurysm size, feature of aneurysm neck, shape, and rupture status might affect the immediate occlusion after EVT. Multivariate logistic regression analysis indicated that ruptured aneurysm, tiny aneurysm, and wide-neck aneurysm were independent influencing factors of complete occlusion of intracranial aneurysm. Aneurysm rupture status, size, feature of aneurysmal neck, and shape might be the independent influencing factors of immediate angiographic results in intracranial aneurysm patients after EVT. Un-ruptured, micro-miniature, narrow-neck, and regular-shaped aneurysms were more probable to be occluded completely.

Single-centre comparison of procedural complications, clinical outcome, and angiographic follow-up between coiling and stent-assisted coiling for posterior communicating artery aneurysms.

Aneurysm recurrence is a principle limitation of endovascular coiling procedures, especially in posterior communicating artery aneurysms, with reported recurrence rates of >30%. The adjunctive use of self-expandable stents has revolutionised the treatment of intracranial aneurysms, especially for complex morphologies, wide necks, or unfavourable dome-to-neck ratios. However, there are limited data concerning a direct comparison between simple coiling and stent-assisted coiling in posterior communicating artery aneurysms. This study aimed to compare the durability and outcomes of coiling versus stent-assisted coiling procedures. Imaging data of patients with posterior communicating artery aneurysms treated with coiling or stent-assisted coiling between January 2008 and October 2012 were retrospectively analysed. The initial angiographic results, procedural complications, and clinical outcomes were assessed at discharge. Imaging follow-up was performed with cerebral angiography. Complete aneurysm occlusion was achieved on initial angiography in 23/56 (41.1%) stent and 83/235 (35.3%) non-stent patients. At the latest follow-up (mean follow-up 14.3 ± 10.4 months for stent and 13.2 ± 9.5 months for non-stent patients), aneurysms had recurred in 5/47 (10.6%) stent and 57/203 (28.1%) non-stent patients (p=0.014). Procedural complications occurred in 6/56 (10.7%) stent and 27/235 (11.5%) non-stent aneurysms. No rebleeding occurred during clinical follow-up (mean duration, 46.7 months). Recurrence rates at the latest follow-up were significantly lower in patients undergoing stent-assisted coiling than those undergoing simple coiling. Thus, use of the stent-assisted neck remodelling technique in the treatment of wide-necked posterior communicating artery intracranial aneurysms appears to improve the long-term clinical outcome.

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.

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.