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Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms

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A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (23 February 2020) | Viewed by 32102

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Special Issue Editors

Dr. Serge Marbacher

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Guest Editor

Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland
Interests: intracranial aneurysm; subarachnoid hemorrhage; delayed cerebral vasospasm; animal models; neurosurgery; aneurysm wall biology

Prof. Dr. John H. Zhang

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Guest Editor

Departments of Anesthesiology and Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA
Interests: cerebral vascular diseases; ischemic and hemorrhagic stroke; neuroprotective strategies; cerebral vascular biology; signaling pathways
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Dear Colleagues,

Subarachnoid hemorrhage (SAH) due to intracranial aneurysm rupture is a devastating event leaving mainly young people in their productive life severely disabled. Although SAH accounts for only 5–10% of all strokes, the disease has a significant socioeconomic impact. Every second patient suffers permanent disability and the estimated litetime cost is more than double that of ischemic stroke. The main culprit for the dismal outcome in SAH patients was mainly attributed to delayed cerebral vasospasm, leading to ischemia and cerebral infarction. Clinical attenuation of cerebral vasospasm was finally achieved by successful translation of prior experimental animal work but functional outcomes in patients remained unimproved. These results eroded the hypothesis of cerebral vasospasm as the single main cause of poor outcome after SAH. Early brain injury emerged as a relatively new entity, embracing multiple and complex pathophysiological mechanisms that take place early after SAH. The exact roles of these early pathological phenomenons are just now being elucidated.

The purpose of this Special Issue is to provide an up-to-date overview of the pathophysiology, experimental treatment approaches, and clinical management of subarachnoid hemorrhage. Original, high-quality research papers, as well as review articles addressing the major research challenges and achievements on the topic, are sought. Potential topics include, but are not limited to, the following: Novel pharmacological therapies; translational and clinical studies; biomarkers in SAH; microcirculatory disturbance; early brain injury; delayed cerebral vasospasm; neurobehavioral aspects; prevention of intracranial aneurysm rupture; epidemiological studies; neuroimaging; clinical guidelines; neurointensive care management; and future perspectives in SAH research.

Dr. Serge Marbacher
Prof. Dr. John H. Zhang
Guest Editors

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Keywords

subarachnoid hemorrhage
neurocritical care management
delayed cerebral vasospasm
early brain injury
neuroinflammation
outcome measures
translational research
animal models

Published Papers (10 papers)

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Editorial

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2 pages, 152 KiB

Open AccessEditorial

Experimental and Clinical Treatment of Subarachnoid Hemorrhage after the Rupture of Saccular Intracranial Aneurysms

by Serge Marbacher and John H. Zhang

Brain Sci. 2020, 10(6), 371; https://doi.org/10.3390/brainsci10060371 - 15 Jun 2020

Cited by 1 | Viewed by 1607

Abstract

The Special Issue “Experimental and Clinical Treatment of Subarachnoid Hemorrhage after the Rupture of Saccular Intracranial Aneurysms” provides an excellent insight into the many facets of aneurysmal subarachnoid hemorrhage [...] Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

Research

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11 pages, 1723 KiB

Open AccessArticle

The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm

by Mieko Oka, Isao Ono, Kampei Shimizu, Mika Kushamae, Haruka Miyata, Takakazu Kawamata and Tomohiro Aoki

Brain Sci. 2020, 10(6), 335; https://doi.org/10.3390/brainsci10060335 - 31 May 2020

Cited by 8 | Viewed by 2603

Abstract

Considering the poor outcome of subarachnoid hemorrhage (SAH) due to the rupture of intracranial aneurysms (IA), mechanisms underlying the pathogenesis of IAs, especially the rupture of lesions, should be clarified. In the present study, a rat model of IAs in which induced lesions spontaneously ruptured resulting in SAH was used. In this model, the combination of the female sex and the bilateral ovariectomy increased the incidence of SAH, similar to epidemiological evidence in human cases. Importantly, unruptured IA lesions induced in female animals with bilateral ovariectomy were histopathologically similar to ruptured ones in the presence of vasa vasorum and the accumulation of abundant inflammatory cells, suggesting the exacerbation of the disease. The post-stenotic dilatation of the carotid artery was disturbed by the bilateral ovariectomy in female rats, which was restored by hormone replacement therapy. The in vivo study thus suggested the protective effect of estrogen from the ovary on endothelial cells loaded by wall shear stress. β-estradiol or dihydrotestosterone also suppressed the lipopolysaccharide-induced expression of pro-inflammatory genes in cultured macrophages and neutrophils. The results of the present study have thus provided new insights about the process regulating the progression of the disease. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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18 pages, 1927 KiB

Open AccessArticle

Endovascular Temporary Balloon Occlusion for Microsurgical Clipping of Posterior Circulation Aneurysms

by Jenny C. Kienzler, Michael Diepers, Serge Marbacher, Luca Remonda and Javier Fandino

Brain Sci. 2020, 10(6), 334; https://doi.org/10.3390/brainsci10060334 - 30 May 2020

Cited by 8 | Viewed by 2864

Abstract

Based on the relationship between the posterior clinoid process and the basilar artery (BA) apex it may be difficult to obtain proximal control of the BA using temporary clips. Endovascular BA temporary balloon occlusion (TBO) can reduce aneurysm sac pressure, facilitate dissection/clipping, and finally lower the risk of intraoperative rupture. We present our experience with TBO during aneurysm clipping of posterior circulation aneurysms within the setting of a hybrid operating room (hOR). We report one case each of a basilar tip, posterior cerebral artery, and superior cerebellar artery aneurysm that underwent surgical occlusion under TBO within an hOR. Surgical exposure of the BA was achieved with a pterional approach and selective anterior and posterior clinoidectomy. Intraoperative digital subtraction angiography (iDSA) was performed prior, during, and after aneurysm occlusion. Two patients presented with subarachnoid hemorrhage and one patient presented with an unruptured aneurysm. The intraluminal balloon was inserted through the femoral artery and inflated in the BA after craniotomy to allow further dissection of the parent vessel and branches needed for the preparation of the aneurysm neck. No complications during balloon inflation and aneurysm dissection occurred. Intraoperative aneurysm rupture prior to clipping did not occur. The duration of TBO varied between 9 and 11 min. Small neck aneurysm remnants were present in two cases (BA and PCA). Two patients recovered well with a GOS 5 after surgery and one patient died due to complications unrelated to surgery. Intraoperative TBO within the hOR is a feasible and safe procedure with no additional morbidity when using a standardized protocol and setting. No relevant side effects or intraoperative complications were present in this series. In addition, iDSA in an hOR facilitates the evaluation of the surgical result and 3D reconstructions provide documentation of potential aneurysm remnants for future follow-up. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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11 pages, 2084 KiB

Open AccessArticle

Comparison of Aneurysm Patency and Mural Inflammation in an Arterial Rabbit Sidewall and Bifurcation Aneurysm Model under Consideration of Different Wall Conditions

by Basil Erwin Grüter, Stefan Wanderer, Fabio Strange, Sivani Sivanrupan, Michael von Gunten, Hans Rudolf Widmer, Daniel Coluccia, Lukas Andereggen, Javier Fandino and Serge Marbacher

Brain Sci. 2020, 10(4), 197; https://doi.org/10.3390/brainsci10040197 - 27 Mar 2020

Cited by 5 | Viewed by 2570

Abstract

Background: Biological processes that lead to aneurysm formation, growth and rupture are insufficiently understood. Vessel wall inflammation and degeneration are suggested to be the driving factors. In this study, we aimed to investigate the natural course of vital (non-decellularized) and decellularized aneurysms in a rabbit sidewall and bifurcation model. Methods: Arterial pouches were sutured end-to-side on the carotid artery of New Zealand White rabbits (vital [n = 6] or decellularized [n = 6]), and into an end-to-side common carotid artery bifurcation (vital [n = 6] and decellularized [n = 6]). Patency was confirmed by fluorescence angiography. After 28 days, all animals underwent magnetic resonance and fluorescence angiography followed by aneurysm harvesting for macroscopic and histological evaluation. Results: None of the aneurysms ruptured during follow-up. All sidewall aneurysms thrombosed with histological inferior thrombus organization observed in decellularized compared to vital aneurysms. In the bifurcation model, half of all decellularized aneurysms thrombosed whereas the non-decellularized aneurysms remained patent with relevant increase in size compared to baseline. Conclusions: Poor thrombus organization in decellularized sidewall aneurysms confirmed the important role of mural cells in aneurysm healing after thrombus formation. Several factors such as restriction by neck tissue, small dimensions and hemodynamics may have prevented aneurysm growth despite pronounced inflammation in decellularized aneurysms. In the bifurcation model, rarefication of mural cells did not increase the risk of aneurysm growth but tendency to spontaneous thrombosis. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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10 pages, 1219 KiB

Open AccessArticle

Systemic and CSF Interleukin-1α Expression in a Rabbit Closed Cranium Subarachnoid Hemorrhage Model: An Exploratory Study

by Davide Marco Croci, Stefan Wanderer, Fabio Strange, Basil E. Grüter, Daniela Casoni, Sivani Sivanrupan, Hans Rudolf Widmer, Stefano Di Santo, Javier Fandino, Luigi Mariani and Serge Marbacher

Brain Sci. 2019, 9(10), 249; https://doi.org/10.3390/brainsci9100249 - 24 Sep 2019

Cited by 6 | Viewed by 2626

Abstract

Background: The inflammatory pathway in cerebrospinal fluid (CSF) leads to delayed cerebral vasospasm (DCVS) and delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). The role of IL-1α has never been evaluated in a rabbit SAH model. The aim of our study is to analyze systemic and CSF changes of IL-1α, and to evaluate potential associations with the onset of DCVS in a rabbit closed cranium SAH model. Methods: 17 New Zealand white rabbits were randomized into two groups, SAH (n = 12) and sham (n = 5). In the first group, SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cerebral cistern of magna under intracranial pressure (ICP) monitoring. The sham group served as a control. The CSF and blood samples for IL-1α measurement were taken at day zero before SAH induction and at day three. Results: There was a significant increase of ICP (p = 0.00009) and a decrease of cerebral perfusion pressure (CPP) (p = 0.00089) during SAH induction. At follow up, there was a significant increase of systemic IL-1α in the SAH as compared with the sham group (p = 0.042). There was no statistically significant difference in the CSF values in both groups. The CSF IL-1α values showed a correlation trend of DCVS. Conclusions: Systemic IL-1α levels are elevated after SAH induction in a rabbit SAH model. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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Review

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25 pages, 1051 KiB

Open AccessReview

The Role of Sartans in the Treatment of Stroke and Subarachnoid Hemorrhage: A Narrative Review of Preclinical and Clinical Studies

by Stefan Wanderer, Basil E. Grüter, Fabio Strange, Sivani Sivanrupan, Stefano Di Santo, Hans Rudolf Widmer, Javier Fandino, Serge Marbacher and Lukas Andereggen

Brain Sci. 2020, 10(3), 153; https://doi.org/10.3390/brainsci10030153 - 7 Mar 2020

Cited by 12 | Viewed by 3898

Abstract

Background: Delayed cerebral vasospasm (DCVS) due to aneurysmal subarachnoid hemorrhage (aSAH) and its sequela, delayed cerebral ischemia (DCI), are associated with poor functional outcome. Endothelin-1 (ET-1) is known to play a major role in mediating cerebral vasoconstriction. Angiotensin-II-type-1-receptor antagonists such as Sartans may have a beneficial effect after aSAH by reducing DCVS due to crosstalk with the endothelin system. In this review, we discuss the role of Sartans in the treatment of stroke and their potential impact in aSAH. Methods: We conducted a literature research of the MEDLINE PubMed database in accordance with PRISMA criteria on articles published between 1980 to 2019 reviewing: “Sartans AND ischemic stroke”. Of 227 studies, 64 preclinical and 19 clinical trials fulfilled the eligibility criteria. Results: There was a positive effect of Sartans on ischemic stroke in both preclinical and clinical settings (attenuating ischemic brain damage, reducing cerebral inflammation and infarct size, increasing cerebral blood flow). In addition, Sartans reduced DCVS after aSAH in animal models by diminishing the effect of ET-1 mediated vasoconstriction (including cerebral inflammation and cerebral epileptogenic activity reduction, cerebral blood flow autoregulation restoration as well as pressure-dependent cerebral vasoconstriction). Conclusion: Thus, Sartans might play a key role in the treatment of patients with aSAH. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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16 pages, 650 KiB

Open AccessReview

Preclinical Intracranial Aneurysm Models: A Systematic Review

by Fabio Strange, Basil E Grüter, Javier Fandino and Serge Marbacher

Brain Sci. 2020, 10(3), 134; https://doi.org/10.3390/brainsci10030134 - 27 Feb 2020

Cited by 27 | Viewed by 4303

Abstract

Intracranial aneurysms (IA) are characterized by weakened cerebral vessel walls that may lead to rupture and subarachnoid hemorrhage. The mechanisms behind their formation and progression are yet unclear and warrant preclinical studies. This systematic review aims to provide a comprehensive, systematic overview of available animal models for the study of IA pathobiology. We conducted a systematic literature search using the PubMed database to identify preclinical studies employing IA animal models. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies were reviewed and categorized according to the experimental animal and aneurysm model. Of 4266 returned results, 3930 articles were excluded based on the title and/or abstract and further articles after screening the full text, leaving 123 studies for detailed analysis. A total of 20 different models were found in rats (nine), mice (five), rabbits (four), and dogs (two). Rat models constituted the most frequently employed intracranial experimental aneurysm model (79 studies), followed by mice (31 studies), rabbits (12 studies), and two studies in dogs. The most common techniques to induce cerebral aneurysms were surgical ligation of the common carotid artery with subsequent induction of hypertension by ligation of the renal arteries, followed by elastase-induced creation of IAs in combination with corticosterone- or angiotensin-induced hypertension. This review provides a comprehensive summary of the multitude of available IA models to study various aspects of aneurysm formation, growth, and rupture. It will serve as a useful reference for researchers by facilitating the selection of the most appropriate model and technique to answer their scientific question. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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10 pages, 1206 KiB

Open AccessFeature PaperReview

Saccular Aneurysm Models Featuring Growth and Rupture: A Systematic Review

by Serge Marbacher, Stefan Wanderer, Fabio Strange, Basil E. Grüter and Javier Fandino

Brain Sci. 2020, 10(2), 101; https://doi.org/10.3390/brainsci10020101 - 13 Feb 2020

Cited by 18 | Viewed by 3269

Abstract

Background. Most available large animal extracranial aneurysm models feature healthy non-degenerated aneurysm pouches with stable long-term follow-ups and extensive healing reactions after endovascular treatment. This review focuses on a small subgroup of extracranial aneurysm models that demonstrated growth and potential rupture during follow-up. Methods. The literature was searched in Medline/Pubmed to identify extracranial in vivo saccular aneurysm models featuring growth and rupture, using a predefined search strategy in accordance with the PRISMA guidelines. From eligible studies we extracted the following details: technique and location of aneurysm creation, aneurysm pouch characteristics, time for model creation, growth and rupture rate, time course, patency rate, histological findings, and associated morbidity and mortality. Results. A total of 20 articles were found to describe growth and/or rupture of an experimentally created extracranial saccular aneurysm during follow-up. Most frequent growth was reported in rats (n = 6), followed by rabbits (n = 4), dogs (n = 4), swine (n = 5), and sheep (n = 1). Except for two studies reporting growth and rupture within the abdominal cavity (abdominal aortic artery; n = 2) all other aneurysms were located at the neck of the animal. The largest growth rate, with an up to 10-fold size increase, was found in a rat abdominal aortic sidewall aneurysm model. Conclusions. Extracranial saccular aneurysm models with growth and rupture are rare. Degradation of the created aneurysmal outpouch seems to be a prerequisite to allow growth, which may ultimately lead to rupture. Since it has been shown that the aneurysm wall is important for healing after endovascular therapy, it is likely that models featuring growth and rupture will gain in interest for preclinical testing of novel endovascular therapies. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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Other

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7 pages, 1300 KiB

Open AccessCase Report

Injury of Corticospinal Tract in a Patient with Subarachnoid Hemorrhage as Determined by Diffusion Tensor Tractography: A Case Report

by Chan-Hyuk Park, Hyeong Ryu, Chang-Hwan Kim, Kyung-Lim Joa, Myeong-Ok Kim and Han-Young Jung

Brain Sci. 2020, 10(3), 177; https://doi.org/10.3390/brainsci10030177 - 19 Mar 2020

Cited by 5 | Viewed by 3764

Abstract

We report diffusion tensor tractography (DTT) of the corticospinal tract (CST) in a patient with paresis of all four limbs following subarachnoid hemorrhage (SAH) with intraventricular hemorrhage (IVH) after the rupture of an anterior communicating artery (ACoA) aneurysm rupture. The 73-year-old female was admitted to our emergency room in a semi-comatose mental state. After coil embolization—an acute SAH treatment—she was transferred to our rehabilitation department with motor weakness development, two weeks after SAH. Upon admission, she was alert but she complained of motor weakness (upper limbs: MRC 3/5, and lower limbs: MRC 1/5). Four weeks after onset, DTT showed that the bilateral CSTs failed to reach the cerebral cortex. The left CST demonstrated a wide spread of fibers within the corona radiata as well as significantly lower tract volume (TV) and higher fractional anisotropy (FA) as well as mean diffusivity (MD) compared to the controls. On the other hand, the right CST shifted to the posterior region at the corona radiata, and MD values of the right CST were significantly higher when compared to the controls. Changes in both CSTs were attributed to vasogenic edema and compression caused by untreated hydrocephalus. We demonstrate in this case, two different pathophysiological entitles, contributing to this patient’s motor weakness after SAH. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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6 pages, 803 KiB

Open AccessCase Report

Syncope as Initial Presentation in an Undifferentiated Type Acute Myeloid Leukemia Patient with Acute Intracranial Hemorrhage

by Meng-Yu Wu, Ching-Hsiang Lin, Yueh-Tseng Hou, Po-Chen Lin, Giou-Teng Yiang, Yueh-Cheng Tien and Hsiao-Ching Yeh

Brain Sci. 2019, 9(8), 207; https://doi.org/10.3390/brainsci9080207 - 20 Aug 2019

Cited by 4 | Viewed by 3642

Abstract

Intracranial hemorrhage (ICH) is a catastrophic complication in patients with acute myeloid leukemia (AML). AML cells, especially in the acute promyelocytic leukemia subtype, may release microparticles (MPs), tissue factor (TF), and cancer procoagulant (CP) to promote coagulopathy. Hyperfibrinolysis is also triggered via release of annexin II, t-PA, u-PA, and u-PAR. Various inflammatory cytokines from cancer cells, such as IL-1β and TNF-α, activate endothelial cells and promote leukostasis. This condition may increase the ICH risk and lead to poor clinical outcomes. Here, we present a case under a unique situation with acute ICH detected prior to the diagnosis of AML. The patient initially presented with two episodes of syncope. Rapidly progressive ICH was noted in follow-up computed tomography (CT) scans. Therefore, we highlight that AML should be among the differential diagnoses of the etiologies of ICH. Early diagnosis and timely intervention are very important for AML patients. Full article

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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