scholarly journals Estrogen Deficiency Promotes Cerebral Aneurysm Rupture by Upregulation of Th17 Cells and Interleukin‐17A Which Downregulates E‐Cadherin

Author(s):  
Brian L. Hoh ◽  
Kelley Rojas ◽  
Li Lin ◽  
Hanain Z. Fazal ◽  
Siham Hourani ◽  
...  
Neurosurgery ◽  
2019 ◽  
Vol 86 (4) ◽  
pp. 583-592 ◽  
Author(s):  
Daisuke Wajima ◽  
Siham Hourani ◽  
William Dodd ◽  
Devan Patel ◽  
Chad Jones ◽  
...  

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.


Author(s):  
Matthias Bechstein ◽  
Amarjargal Gansukh ◽  
Boldbat Regzengombo ◽  
Oyun Byambajav ◽  
Lukas Meyer ◽  
...  

Abstract Purpose Identification of country-specific demographic, medical, lifestyle, and geoenvironmental risk factors for cerebral aneurysm rupture in the developing Asian country of Mongolia. First-time estimation of the crude national incidence of aneurysmal subarachnoid hemorrhage (aSAH). Methods A retrospective analysis of all intracranial digital subtraction angiographies (DSA) acquired in Mongolia during the 2‑year period 2016–2017 (1714 examinations) was performed. During this period, DSA was used as primary diagnostic imaging modality for acute severe neurological symptoms in the sole hospital nationwide dedicated to neurological patients. The catchment area of the hospital included the whole country. Patients with incidental and ruptured aneurysms were reviewed with respect to their medical history and living conditions. The data was used to install a Mongolian aneurysm registry. Results The estimated annual crude incidence of cerebral aneurysm rupture was 6.71 for the country of Mongolia and 14.53 per 100,000 persons for the capital region of Ulaanbaatar. Risk factors common in developed countries also applied for the Mongolian population: A medical history of hypertension, smoking or the presence of multiple aneurysms led to a higher relative risk of rupture. In contrast, female gender was not associated with a higher risk in this national cohort. Males pursuing a traditional nomadic living may exhibit a specifically high risk of rupture. Conclusion Disease management of over 200 individuals/year with aSAH constitutes a socioeconomic burden in Mongolia. Efforts to raise awareness of the risk factors hypertension and smoking among the Mongolian population are desirable. Measures to improve the nationwide availability of modern neurovascular treatment options are currently under consideration.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Gwendolyn K Davis ◽  
Daniel Fehrenbach ◽  
Charles D Smart ◽  
Claudia Edell ◽  
Jennifer Pollock ◽  
...  

Circadian rhythms govern our daily physiological processes. However, disruption of circadian rhythms, as can occur with ad libitum Western diets, disrupt these processes leading to cardiometabolic diseases. Our lab and others have shown that Th17 cells, which produce interleukin 17A (IL-17A), are implicated in the development of cardiovascular and renal end-organ damage associated with high fat and/or high salt diets. Th17 cell differentiation and trafficking is regulated by the circadian clock and influenced by light-dark cycles. However, whether feeding-fasting rhythms influence Th17 cell responses is poorly understood. We tested the hypothesis that limiting food intake to the 12-hr active period (time-restricted feeding, TRF) mitigates high fat and high salt (HF/HS) diet induced T cell IL-17A production and target organ damage. Beginning at 8 weeks of age, male C57Bl/6J mice were placed on either a normal chow/normal salt (NC/NS) or a HF/HS diet for 20 weeks, with TRF intervention occurring during the last two weeks in the HF/HS + TRF group. Body weight was similarly significantly increased in the HF/HS and HF/HS + TRF groups in comparison to the NC/NS group. Th17 cells were significantly increased (2.6-fold increase, p = 0.02) in the Peyer’s patches (lymphoid aggregates found in the small intestines) of mice on HF/HS diet in comparison to those on NC/NS. Importantly, TRF abolished this increase. Renal CD4 + T cell IL-17A production, as measured by flow cytometry, was increased by HF/HS diet compared to NC/NS (3-fold increase, p = 0.02). Similarly, TRF abolished this increase. This study highlights how Western diets exacerbate intestinal and renal IL-17A production and the potential beneficial impact of a behavioral intervention, TRF, to mitigate the Th17 mediated inflammation associated with diet-induced obesity.


Author(s):  
Felicitas J. Detmer ◽  
Daniel Lückehe ◽  
Fernando Mut ◽  
Martin Slawski ◽  
Sven Hirsch ◽  
...  

2019 ◽  
Vol 47 (1) ◽  
pp. E20 ◽  
Author(s):  
John W. Thompson ◽  
Omar Elwardany ◽  
David J. McCarthy ◽  
Dallas L. Sheinberg ◽  
Carlos M. Alvarez ◽  
...  

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.


Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 338
Author(s):  
Stojanović ◽  
Kostić ◽  
Mitić ◽  
Berilažić ◽  
Radisavljević

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.


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