scholarly journals Interleukin-6 Promotes Murine Estrogen Deficiency-Associated Cerebral Aneurysm Rupture

Neurosurgery ◽  
2019 ◽  
Vol 86 (4) ◽  
pp. 583-592 ◽  
Author(s):  
Daisuke Wajima ◽  
Siham Hourani ◽  
William Dodd ◽  
Devan Patel ◽  
Chad Jones ◽  
...  
Keyword(s):  
Cerebral Aneurysm ◽  
Cerebral Aneurysms ◽  
Neutralizing Antibody ◽  
Aneurysm Rupture ◽  
Estrogen Deficiency ◽  
Circle Of Willis ◽  
Macrophage Infiltration ◽  
Wild Type ◽  
Rupture Rate ◽  
Deficient Mice

Abstract BACKGROUND Estrogen deficiency is associated with cerebral aneurysm rupture, but the precise mechanism is unknown. OBJECTIVE To test the hypothesis that IL-6 is required for the increase in aneurysm rupture rate observed in estrogen-deficient mice. METHODS We analyzed IL-6 expression in human cerebral aneurysms. We induced cerebral aneurysms in estrogen-deficient female C57BL/6 mice that had undergone 4-vinylcyclohexene diepoxide (VCD) treatment or bilateral ovariectomy (OVE). Mice were blindly randomized to selective IL-6 inhibition (IL-6 receptor [IL-6R] neutralizing antibody, n = 25) or control (isotype-matched IgG, n = 28). Murine cerebral arteries at the circle of Willis were assessed for aneurysm rupture and macrophage infiltration. RESULTS IL-6 is expressed in human cerebral aneurysms, but not in control arteries. Serum IL-6 is elevated in ovariectomized female mice compared to sham control (14.3 ± 1.7 pg/mL vs 7.4 ± 1.5 pg/mL, P = .008). Selective IL-6R inhibition suppressed cerebral aneurysm rupture in estrogen-deficient mice compared with control (VCD: 31.6% vs 70.0%, P = .026; OVE: 28.6% vs 65.2%, P = .019). IL-6R inhibition had no effect on formation or rupture rate in wild-type mice. IL-6R neutralizing antibody significantly reduced macrophage infiltration at the circle of Willis (1.9 ± 0.2 vs 5.7 ± 0.6 cells/2500 μm2; n = 8 vs n = 15; P < .001). CONCLUSION IL-6 is increased in the serum of estrogen-deficient mice and appears to play a role in promoting murine estrogen deficiency-associated cerebral aneurysm rupture via enhanced macrophage infiltration at the circle of Willis. Inhibition of IL-6 signaling via IL-6 receptor neutralizing antibody inhibits aneurysm rupture in estrogen-deficient mice. IL-6 receptor inhibition had no effect on aneurysm formation or rupture in wild-type animals.

scholarly journals Association between Circle of Willis Configuration and Rupture of Cerebral Aneurysms

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 338
Author(s):  
Stojanović ◽  
Kostić ◽  
Mitić ◽  
Berilažić ◽  
Radisavljević
Keyword(s):  
Cerebral Aneurysm ◽  
Intracranial Hemorrhage ◽  
Lower Incidence ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Circle Of Willis ◽  
Type B ◽  
Brain Aneurysms

Background and Objectives: Intracranial hemorrhage caused by the rupture of brain aneurysms occurs in almost 10 per 100,000 people whereas the incidence of such aneurysms is significantly higher, accounting for 4–9%.Linking certain factors to cerebral aneurysm rupture could help in explaining the significantly lower incidence of their rupture compared to their presence. The aim of this study is to determine the association between the corresponding circle of Willis configurations and rupture of cerebral aneurysms. Materials and Methods: A group of 114 patients treated operatively for aruptured cerebral aneurysm and a group of 56 autopsied subjects were involved in the study. Four basic types of the circle of Willis configurations were formed—two symmetric types A and C, and two asymmetric types B and D. Results: A statistically significantly higher presence of asymmetry of the circle of Willis was determined in the group of surgically-treated subjects (p = 0.001),witha significant presence of asymmetric Type B in this group (p < 0.001). The changeson the A1 segment in the group of surgically-treated subjects showed a statistically significant presence compared to the group of autopsied subjects (p = 0.001). Analyzing the presence of symmetry of the circle of Willis between the two groups, that is, the total presence of symmetric types A and C, indicated their statistically significant presence in the group of autopsied patients (p < 0.001). Conclusions: Changes such as hypoplasia or aplasia of A1 and the resulting asymmetry of the circle of Willis directly affect the possibility of the rupture of cerebral aneurysms. Detection of the corresponding types of the circle of Willis after diagnostic examination can be the basis for the development of a protocol for monitoring such patients.

scholarly journals Influence of Circle of Willis Configuration on the Rupture of Cerebral Aneurysms

2019 ◽  
Author(s):  
Stojanović N. Nebojša ◽  
Kostić Aleksandar ◽  
Mitić Radisav ◽  
Berilažić Luka ◽  
Radisavljević Miša
Keyword(s):  
Cerebral Aneurysm ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Circle Of Willis ◽  
Anterior Communicating Artery ◽  
Type B

Background: Formation and rupture of cerebral aneurysms may be related to certain types of configuration of the circle of Willis. Analysis of their interdependence can be of great importance. Methods: A group of 114 patients treated operatively for the cerebral aneurysm rupture and a group of 56 autopsied subjects were involved in the study. Four basic types of the circle of Willis configurations were formed&ndash;two symmetric types A and C, and two asymmetric types B and D. Results: A statistically significantly higher presence of asymmetry of the circle of Willis in the group of surgically treated subjects (p=0.006) with a significant presence of asymmetric Type B in this group (p=0.017) were determined. The presence of changes in the A1 segment in the group of subjects with solitary aneurysms on the anterior communicating artery showed a statistically significant presence in the group of autopsied subjects (p=0.0004). Analyzing the presence of symmetry of the circle of Willis between the two groups, that is, the total presence of symmetric types A and C indicated their statistically significant presence in the group of autopsied patients (p=0.043). Conclusion: Changes such as hypoplasia or aplasia of A1 and the resulting asymmetry of the circle of Willis directly affect the possibility of the rupture of cerebral aneurysms. Detection of the corresponding types of the circle of Willis after diagnostic examination can be the basis for the development of a protocol for monitoring such patients.

Abstract TP80: Incidence And Risk Factors For The Growth And Rupture Of Unruptured Cerebral Aneurysms. Results Of Annual Radiologic Follow Up Study.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Katsumi Matsumoto ◽  
Kouichirou Tsuruzono ◽  
Manabu Sasaki ◽  
Noriyasu Yoshimura ◽  
Toshiki Yoshimine ◽  
...  
Keyword(s):  
Growth Rate ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Annual Growth ◽  
Annual Growth Rate ◽  
Rupture Rate ◽  
Follow Up Study ◽  
Factors Influencing ◽  
Unruptured Cerebral Aneurysms

Background: The recent trend of the treatment of unruptured cerebral aneurysms(UIAs) is going to be conservative. Their natural history of rupture and growth is still unkown. We present the results of annual radiological follow-up study in UIAs. Method: In recent 12 years, we have found 121patients with 148 unruptured cerebral aneurysms were followed annually using 3D-CTA or MRA. Mean follow-up period was 5.5 year. Several factors influencing rupture or growth were statistically examined. Results: Among 121 patients, 9 ruptured and 11 showed growth of UIAs. Annual rupture rate was 1.3% per year and annual growth rate was 1.6% per year. Aneurysm size was the sole factor influencing rupture(P<0.001), whereas female sex and multiplicity were major factors influencing aneurysm growth(P<0.05). Under size 3mm, annual growth rate was 3.0% whereas annual rupture rate was 0.7%. In 4-6mm, growth rate was 1.6% and rupture rate was 1.6%. In 7-9mm, growth rate was 0 and rupture rate was 5.8%. In over 10mm, growth rate was 2.9% and rupture rate was 11.6%. Within 1 year, rupture occurred in 4 cases, and growth was found in 1 case. Conclusions: By annual radiological examination, growth of UIAs was noted more frequently than aneurysm rupture. Especially UIAs under 3mm, growth was 4 times higher than rupture, radiological follow up is effective for aneurysm rupture. Within 1 year, initially found UIAs should be carefully followed in a short interval.

scholarly journals In vivo cerebral aneurysm models

2019 ◽  
Vol 47 (1) ◽  
pp. E20 ◽  
Author(s):  
John W. Thompson ◽  
Omar Elwardany ◽  
David J. McCarthy ◽  
Dallas L. Sheinberg ◽  
Carlos M. Alvarez ◽  
...  
Keyword(s):  
Cerebral Aneurysm ◽  
Surgical Techniques ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Large Animal ◽  
Pharmacological Interventions ◽  
Large Animal Models ◽  
First Line Therapy ◽  
Endovascular Devices

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.

Size is the Most Important Predictor of Aneurysm Rupture Among Multiple Cerebral Aneurysms: Post Hoc Subgroup Analysis of Unruptured Cerebral Aneurysm Study Japan

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 864-869 ◽  
Author(s):  
Masaaki Shojima ◽  
Akio Morita ◽  
Hirofumi Nakatomi ◽  
Shinjiro Tominari
Keyword(s):  
Cerebral Aneurysm ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Ruptured Aneurysm ◽  
Clinical Value ◽  
Total Cohort ◽  
Unruptured Cerebral Aneurysm ◽  
Specific Factors ◽  
Unruptured Cerebral Aneurysms ◽  
Post Hoc

Abstract BACKGROUND Multiple cerebral aneurysms are encountered in approximately 15% to 35% of patients harboring unruptured cerebral aneurysms. It would be of clinical value to determine which of them is most likely to rupture. OBJECTIVE To characterize features of the ruptured aneurysm relative to other concomitant fellow aneurysms in patients with multiple cerebral aneurysms. METHODS From a total of 5720 patients who were prospectively registered in the Unruptured Cerebral Aneurysm Study in Japan, a subgroup of patients with multiple cerebral aneurysms who developed subarachnoid hemorrhage was extracted for this post hoc analysis. Intrapatient comparisons of each aneurysm were carried out using aneurysm-specific factors such as size, location, and shape to identify predictors of rupture among the fellow aneurysms in a patient with multiple cerebral aneurysms. RESULTS Twenty-five patients with 62 aneurysms were identified from the total cohort of 5720 patients. With the distinctiveness in size, which means the aneurysm was the single largest among the multiple aneurysms, the ruptured aneurysm in each case was discriminated from the other coexisting aneurysms with a sensitivity of 0.76 and specificity of 0.86. CONCLUSION Our results suggest that the largest aneurysm is likely to rupture among coexisting aneurysms in a patient with multiple cerebral aneurysms.

scholarly journals The role of anatomical anomalies in anterior communicating artery aneurysm rupture

2013 ◽  
Vol 19 (3) ◽  
pp. 147-153
Author(s):  
Cr.P Dimitriu ◽  
C. Ionescu ◽  
P. Bordei ◽  
I. Bulbuc
Keyword(s):  
Cerebral Artery ◽  
Anterior Cerebral Artery ◽  
Cerebral Aneurysms ◽  
Artery Aneurysm ◽  
Aneurysm Rupture ◽  
Circle Of Willis ◽  
Control Group ◽  
Anterior Communicating Artery ◽  
Aneurysm Size ◽  
Proper Patient Selection

Abstract Background and purpose:limited data exist to guide proper patient selection for preventive treatment of unruptured cerebral aneurysms. Cerebral aneurysms have been associated with anomalies of arterial segments that are forming the brain arterial circle of Willis but whether this association is also related to aneurysm rupture is not known. The occurrence of cerebral aneurysm rupture when a circle of Willis anomaly was present or absent was compared. Material and methods: we have performed this study on a number of 312 cases, of which 87 were dissections, 22 dissection followed by plastic injection, 135 magnetic resonance angiography (MRA), 75 computer tomography angiography (CTA), 40 digital subtraction angiographies (DSA), 30 in vivo (intraoperatory) observation. Brain vascular imaging was reviewed for aneurysm size, morphology and presence of anterior cerebral artery anomalies. Results: we divided the study group in 2 cohorts, one control group of 272 cases, in which we have study the anatomical variants occurrence and aneurysm occurrence in general population and another included 45 patients admitted thru emergency room for subarachnoid hemorrhage, of those 38 were ruptured aneurysm of anterior communicating artery (ACoA). Mean aneurysm size was 8.9 mm. An anterior cerebral artery anomaly was identified in 31 cases (81.5%). Multivariate analysis revealed a higher risk of aneurysm rupture when an anterior cerebral artery was present. Conclusions: this study shows that anterior cerebral artery anomalies are more commonly found in ruptured as opposed to unruptured ACoA aneurysms. The presence of an ACA anomaly may be an important characteristic for selecting patients for preventive aneurysm treatment.

scholarly journals Predicting Cerebral Aneurysm Rupture by Gradient Boosting Decision Tree using Clinical, Hemodynamic, and Morphological Information

10.29007/jjwt ◽  
2020 ◽  
Author(s):  
Toshiyuki Haruhara ◽  
Hideto Ohgi ◽  
Masaaki Suzuki ◽  
Hiroyuki Takao ◽  
Takashi Suzuki ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Cerebral Aneurysm ◽  
Cerebral Aneurysms ◽  
Prediction Method ◽  
Preventive Treatment ◽  
Aneurysm Rupture ◽  
Gradient Boosting ◽  
Machine Learning Model ◽  
The Individual ◽  
Shape Data

Stroke is a serious cerebrovascular condition in which brain cells die due to an abrupt blockage of arteries supplying blood and oxygen or when a blood vessel bursts or ruptures and causes bleeding in the brain. Because the onset of stroke is very sudden in most people, prevention is often difficult. In Japan, stroke is one of the major causes of death and is associated with high medical costs; these problems are exacerbated by the aging population. Therefore, stroke prediction and treatment are important. The incidence of stroke may be avoided by preventive treatment based on the patient’s risk of stroke. However, since judging the risk of stroke onset is largely dependent upon the individual experience and skill of the doctor, a highly accurate prediction method that is independent of the doctor’s experience and skills is necessary. This study focuses on a predictive method for subarachnoid hemorrhage, which is a type of stroke. LightGBM was used to predict the rupture of cerebral aneurysms using a machine learning model that takes clinical, hemodynamic and morphological information into account. This model was used to analyze samples from 338 cerebral aneurysm cases (35 ruptured, 303 unruptured). Simulation of cerebral blood-flow was used to calculate the hemodynamic features while the surface curvature was extracted from the 3D blood-vessel-shape data as morphological features. This model yielded a sensitivity of 0.77 and a specificity of 0.83.

scholarly journals Inflammation in Murine Aneurysm Healing: The Role of CXCL1

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Devan Patel ◽  
Kartik Motwani ◽  
Koji Hosaka ◽  
Brian L Hoh
Keyword(s):  
Data Collection ◽  
Cerebral Aneurysm ◽  
Treatment Options ◽  
Neutralizing Antibody ◽  
Neutrophil Infiltration ◽  
Flow Chamber ◽  
Aneurysm Rupture ◽  
Endovascular Coiling ◽  
The Right

Abstract INTRODUCTION Cerebral aneurysm rupture results in subarachnoid hemorrhage which has a mortality of up to 40%. Current prophylactic treatment options include surgical clipping, flow diversion, and endovascular coiling. A significant drawback of coiling is that up to 20% of aneurysms recur and require retreatment due to insufficient fibrotic healing. Thus, it is crucial to develop more effective treatments. As inflammation appears to be critical in cerebral aneurysm pathophysiology, it is necessary to investigate aneurysm healing in the context of key inflammatory mediators. Using a novel in Vitro flow chamber model, we found increased expression of CXCL1, a neutrophil chemoattractant, at arterial bifurcations and in aneurysms. We hypothesized that CXCL1 is a key mediator in aneurysm healing. METHODS Using our murine aneurysm healing model, aneurysms were created in the right common carotid artery of female C57BL/6 mice using elastase. Three weeks later, aneurysms were implanted with either poly (lactic-co-glycolic acid) (PLGA) + CXCL1—coated coils or PLGA only—coated coils. Three weeks after coil implantation, aneurysms were harvested for data collection. In a subsequent experiment, the same aneurysm model was used but all mice were coiled with PLGA-coated coils. Animals were randomly assigned to receive intraperitoneal injections of either CXCL1 neutralizing antibody or IgG control. Three weeks after coiling, aneurysms were harvested for data collection. RESULTS Animals treated with PLGA + CXCL1—coated coils had significantly decreased aneurysm healing than those treated with PLGA only—coated coils (21.8% vs 39.8%, P = .048). Animals treated with CXCL1 neutralizing antibody had significantly increased aneurysm healing compared to IgG control (63.8% vs 42.4%, P = .00012). CXCL1 neutralizing antibody also decreased neutrophil infiltration into the aneurysm compared to IgG control (2.0 cells/hpf vs 5.4 cells/hpf, P = .03). CONCLUSION Our findings suggest CXCL1 decreases murine aneurysm healing after coil implantation. Therapeutic intervention with CXCL1 neutralizing antibody appears to increase aneurysm healing by decreasing neutrophil infiltration.

Abstract 2731: CFD Reveals Hemodynamic Differences Between Unruptured And Ruptured Intracranial Aneurysms During Observation

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Hiroyuki Takao ◽  
Yuichi Murayama ◽  
Toshihiro Ishibashi ◽  
Ichiro Yuki ◽  
Shinobu Otsuka ◽  
...  
Keyword(s):  
Cerebral Aneurysm ◽  
Significant Risk ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Medium Size ◽  
Hemodynamic Parameters ◽  
Natural Risk ◽  
Risk Of Rupture ◽  
Significant Difference

Background and Purpose: Although various studies have been performed, the mechanism leading to the rupture of cerebral aneurysms has not yet been elucidated. Accurate assessment of cerebral aneurysm rupture risk is important because current treatments carry a small but significant risk that can exceed the small natural risk of rupture. Various hemodynamic parameters have been proposed for estimating the risk of rupture of cerebral aneurysms, with limited success. We evaluated several hemodynamic parameters to predict rupture in a dataset of initially unruptured aneurysms in which some aneurysms ruptured during follow-up observation. Methods: Geometry of the aneurysm and blood vessels was extracted from CTA images and analyzed using a mathematical formula for fluid flow under pulsatile blood flow conditions. Fifty side-wall internal carotid posterior communicating artery (ICA-pcom) aneurysms and fifty middle cerebral artery (MCA) bifurcation aneurysms of medium size were investigated for Energy loss (EL), Pressure Loss Coefficient (PLC), wall-shear-stress (WSS) and oscillatory shear index (OSI). During a follow-up observation period, 6 ICA-pcom and 7 MCA aneurysms ruptured (44 and 43 remained unruptured, respectively, with the same location and a similar size as the ruptured cases). Results: A significant difference in the minimum WSS between aneurysms that ruptured and those that remained unruptured was noted only in ICA aneurysms (P<0.001). EL showed higher tendency in ruptured aneurysms but statistically not significant. For PLC, a significant difference was noted in both ICA (P<0.001) and MCA (P<0.001) aneurysms. All other parameters did not show significant differences between the two groups. Conclusion: A significant difference was noted in WSSMIN only in ICA aneurysms. For PLC, a significant difference was noted in both ICA and MCA aneurysms, suggesting that PLC may be one, out of possibly other useful parameters to predict cerebral aneurysm rupture.

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