Intra-aneurysmal contrast agent stasis during intraoperative digital subtraction angiography may predict long-term occlusion after clipping.

PURPOSE: The routine use of intraoperative digital subtraction angiography (iDSA) increases detection of intracranial aneurysm (IA) remnants after microsurgical clipping. Spontaneous thrombosis of IA remnants after clipping is considered a rare phenomenon. We analyse iDSA characteristics to find predictors for IA remnant thrombosis. METHODS: IA with intraoperative detection of a remnant after clipping were identified and divided into remnants experiencing spontaneous thrombosis, and remnants with long-term patency and/or remnant growth. Angiographic features of iDSA were analysed and compared between the two groups. RESULTS: Of 37 IAs with intraoperative remnant on 3D-iDSA, five sustained a spontaneous remnant thrombosis and remained occluded in long-term follow-up. In all five cases, iDSA revealed delayed inflow and consequent stasis of the contrast agent until the late venous phase. On the other hand, in all cases with persistent long-term IA remnants (n = 32) iDSA demonstrated timely arterial contrast inflow and wash-out without stasis of intra-aneurysmal contrast agent. CONCLUSIONS: Contrast stasis in IA remnants during iDSA appears to predict long-term IA occlusion, indicating that clip correction manoeuvres or even attempted endovascular treatment of the remnant IA may be avoided in these patients.

Topographic distribution of inflammation factors in a healing aneurysm.

BACKGROUND: Healing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing. METHODS: Decellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall. RESULTS: Coiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing. CONCLUSION: The presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.

Trends in Literature on Cerebral Bypass Surgery: A Systematic Review.

INTRODUCTION: Ever since the beginning of cerebral bypass surgery, the role of the bypass has been debated and indications have changed over the last 5 decades. This systematic literature research analysed all clinical studies on cerebral bypass that have been published from January 1959 to January 2020 for their year of publication, country of origin, citation index, role of and indication for bypass, bypass technique, revascularized territory, flow capacity, and title (for word cloud analysis per decade). METHODS: A systematic literature research was conducted using PubMed, Web of Science, EMBASE, and SCOPUS databases. All studies that have been published until January 1, 2020, were included. RESULTS: Of 6,013 identified studies, 2,585 were included in the analysis. Of these, n = 1,734 (67%) studies addressed flow-augmentation bypass and n = 701 (27%) addressed flow-preservation bypass. The most common indication reported for flow augmentation is moyamoya (n = 877, 51%), followed by atherosclerotic steno-occlusive disease (n = 753, 43%). For flow preservation, the most common indication is studies reporting on cerebral aneurysm surgery (n = 659, 94%). The increasing popularity of reporting on these bypass operations almost came to an end with the FDA approval of flow diverters for aneurysm treatment in 2011. Japan is the country with the most bypass studies (cumulatively published 933 articles), followed by the USA (630 articles) and China (232 articles). DISCUSSION/CONCLUSION: Clinical studies on cerebral bypass surgery have become increasingly popular in the past decades. Since the introduction of moyamoya as a distinct pathologic entity, Asian countries in particular have a very active community regarding this disease, with an increasing number of articles published every year. Studies on bypass for chronic steno-occlusive disease peaked in the 1980s but have remained the main focus of bypass research, particularly in many European departments. The number of reports published on these bypass operations significantly decreased after the FDA approval of flow diverters for aneurysm treatment in 2011.

Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using PubMed to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients.

Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model.

BACKGROUND AND PURPOSE: Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. METHODS: Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. RESULTS: In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; P=0.008). CONCLUSIONS: Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.

Carotid-cavernous sinus fistula following mechanical thrombectomy in acute ischaemic stroke: a rare complication.

Carotid-cavernous sinus fistulas (CCFs) are abnormal communications between the internal carotid artery (ICA) and the cavernous sinus (CS). Direct CCFs are associated with trauma or are iatrogenic complications of neuroendovascular procedures. Meanwhile, mechanical endovascular thrombectomy (MT) in acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO) has been established as a common treatment approach. However, MT is not without its risks of complications, and only a few reports exist on CCF occurring after MT. Here, we present a case of a 63-year-old patient with iatrogenic high-flow CCF of the right horizontal cavernous ICA segment (C4) following repeated MT due to LVO of the middle cerebral artery, and the recent literature is reviewed.

Systematic review of brain arteriovenous malformation grading systems evaluating microsurgical treatment recommendation.

When evaluating brain arteriovenous malformations (bAVMs) for microsurgical resection, the natural history of bAVM rupture must be balanced against the perioperative risks. It is therefore adamant to have a reliable surgical grading system, balancing these important factors. This study systematically reviews the literature in order to identify and assess the quality of grading systems with regard to microsurgical bAVM treatment. A systematic literature review was performed to provide an overview of all available bAVM grading systems relevant for microsurgical treatment evaluation and to assess the most comprehensive grading system specifically for each subgroup of bAVM (i.e., unruptured, ruptured, and posterior fossa). Screening of 865 papers revealed thirteen grading systems for bAVM microsurgical risk stratification. Among them, two systems were specifically developed for ruptured bAVM and one specifically for posterior fossa bAVM. With one system being fundamentally different for supratentorial bAVM, the remaining nine systems used the same parameters: "size," "eloquence," "venous drainage," "arterial feeders," "age," "nidus compactness," and "hemorrhagic presentation". This study provides a comprehensive overview of all available bAVM grading systems relevant for surgical risk stratification. Furthermore, in the absence of a universal system appropriate to score all bAVMs, a workflow for selection of the best applicable scoring system in accordance with bAVM subgroups is presented.

Combined Microsurgical and Endovascular Intracranial Aneurysm Treatment: Interdisciplinary Experience Using a True Hybrid Approach and a Systematic Review of the Literature.

(1) Background: Most intracranial aneurysms (IAs) can be treated either with microsurgical clipping or endovascular techniques. In a few cases, simultaneous treatment utilizing both modalities in a hybrid operation room may be favorable. This study analyzes the indication and benefits of a true hybrid approach (tHA) that combines simultaneous endovascular and microsurgical procedures for treatment of IAs in one session. (2) Methods: All patients receiving a true hybrid procedure between 2010 and 2022 in our institution were included. Demographic characteristics, neurological symptoms, pre-interventional treatments, angiographic findings, and postoperative clinical and radiological outcomes were analyzed. Results are discussed in the light of a systematic literature review on reported true hybrid procedures for IA treatment. (3) Results: In total, 10 tHAs were performed. Of these, coiling and concomitant decompressive craniectomy or hematoma evacuation was performed on six occasions. In two patients, multiple IAs were treated with different modalities during the same procedure. In two patients, intraoperative conditions did not allow for complete IA clipping, and the remnant was coiled in the same session. The review of the literature revealed nine papers comprising 58 IAs treated with a tHA. (4) Conclusions: The need for a tHA for IA treatment is rare and limited to highly selective cases. In our experience, tHAs have been most valuable in an emergency setting concerning ruptured IAs. Furthermore, tHAs may also be considered in patients with multiple aneurysms in different vascular territories.

From conservative to interventional management in unruptured intracranial aneurysms.

OBJECTIVE: Indication for treatment of unruptured intracranial aneurysms (UIAs) is based on several factors, such as patient age, previous medical history, and UIA location and size. For patients harboring UIAs initially managed noninvasively, the treatment strategy during follow-up (FU) can be changed to include surgical or endovascular intervention. This study aims to identify characteristic patterns and potential predictors of UIAs that require revision of the initial management strategy. METHODS: The authors identified intracranial aneurysm (IA) cases newly diagnosed between 2006 and 2022 and initially assigned conservative management. These cases were retrospectively reviewed for 1) patient and UIA characteristics at the time of diagnosis (patient age, comorbidities, previous medical history, potential risk factors, as well as UIA angioarchitecture, location, and size), and 2) any changes in treatment strategy (reason for change, time until intervention, modality of intervention). RESULTS: Among 1041 IA cases diagnosed in the study period, 144 were initially assigned conservative management. In 10 (6.9%) of these 144 cases, the treatment indication was modified to microsurgical clipping (n = 6) or endovascular embolization (n = 4) after a median FU of 26 months (IQR 8.5-64.5 months). In these 10 cases, the indication for intervention was attributable to IA growth (n = 7), a change in IA configuration (n = 2), or both (n = 1). Exploratory analyses of the effects of UIA size on diagnosis in terms of the hazard for a change of decision suggested an effect starting from 3 mm. No conservatively managed UIAs (n = 144) ruptured during the study period (median FU 24.5 months, IQR 7.75-55.75 months). CONCLUSIONS: The likelihood of a shift to invasive UIA treatment is relatively low if a conservative therapeutic strategy was initially established. However, for cases with changes to the treatment strategy, the change is most often attributable to UIA growth over time. UIAs measuring < 3 mm at initial diagnosis are less likely to be later treated interventionally than those > 3 mm at diagnosis. Therefore, conservatively managed patients with UIAs should be closely monitored with regular radiographic FUs, particularly if the UIA measured > 3 mm at the time of diagnosis.

Long-Term Hemorrhage and Reperfusion Rates of Coiled Aneurysms: A Single-Center Experience.

Background: The endovascular approach has emerged as standard therapy for many intracranial aneurysms (IAs) to prevent hemorrhage, yet its long-term durability varies considerably. The aim of this study was to evaluate the safety and effectiveness of an initially deliberate endovascular approach regarding IA hemorrhage rates over a long-term follow-up period. Methods: This retrospective single-center study included all consecutive patients with endovascularly treated IAs who presented between January 2008 and December 2020 with a follow-up of at least 12 months. The primary endpoint was the proportion of patients with long-term IA hemorrhage rates and reperfusion. The secondary endpoint was treatment-related morbidity and mortality. Independent risk factors for IA reperfusion over the long term were analyzed using multivariate logistic regression. Results: Endovascular treatment was the therapy of choice for 333 patients with IAs, among whom 188 (57%) experienced rupture upon presentation. Complete coiling (Raymond I) was noted in 162 (49%) of the patients, with primary supportive devices being used in 51 (15%) patients. After a median (±SD) follow-up time of 34 ± 41 months (range 12-265 months), IA reperfusion was noted in 158 (47%), necessitating retreatment in 105 (32%) of the patients. Over the long term, hemorrhage was noted in four (1%) patients. Multivariate analysis revealed aneurysmal multilobarity (HR 1.8, 95%CI 1.2-2.7; p = 0.004) and a patient age of ≥50 years (HR 1.7, 95% CI 1.1-2.5, p = 0.01) as independent predictors of reperfusion over time. Intervention-related morbidity was noted in 16 (4.8%) patients, namely, thrombosis formation and contrast extravasation in 8 (2.4%) patients each, while no intervention-induced mortality was observed. Conclusion: In the long term, the hemorrhage rate in patients with IA with an initially more conservative endovascular approach is low. Therefore, a deliberate endovascular treatment approach might be justified.

Cerebral Aneurysm and Interleukin-6: a Key Player in Aneurysm Generation and Rupture or Just One of the Multiple Factors?

Intracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased rupture risk, however, are associated with higher levels of IL-6. By better understanding the relationships between IL-6 and IA formation and rupture, IL-6 may serve as a biomarker in high-risk populations. Furthermore, by better understanding the IL-6 signaling mechanisms in IA formation and rupture, IL-6 may optimize surveillance and treatment strategies. This review examines the association between IL-6 and IA, while also suggesting future research directions.

Anatomical Variations of the Common Carotid Arteries and Neck Structures of the New Zealand White Rabbit and Their Implications for the Development of Preclinical Extracranial Aneurysm Models.

BACKGROUND: Rabbit models involving neck arteries are of growing importance for the development of preclinical aneurysm models. An optimal understanding of the anatomy is primordial to allow the conception of models while minimizing mortality and morbidity. The aim of this study is to give reliable anatomical landmarks to allow a standardized approach to the neck vessels. METHODS: We performed a necropsy on nine specimens from ongoing experimental studies. We measured the distance between the origins of the right and left common carotid artery (rCCA/lCCA) and between the rCCA and the manubrium sterni (MS). The structures at risk were described. RESULTS: Female New Zealand White rabbits (NZWR) weighing 3.7 ± 0.3 kg and aged 25 ± 5 weeks were included. The rCCA origin was located 9.6 ± 1.2 mm laterally and 10.1 ± 3.3 mm caudally to the MS. In all specimens, the lCCA originated from the aortic arch, together with the brachiocephalic trunk (BCT), and 6.2 ± 3.1 mm proximally to the rCCA origin. The external and internal jugular veins, trachea and laryngeal nerve were the main structures at risk. CONCLUSIONS: The data help to localize both CCAs and their origin to guide surgical approaches with the manubrium sterni as a main landmark. Special attention has to be paid to the trachea, jugular veins and laryngeal nerves.

Incidence and Outcome of Peri-interventional Vasospasm During Endovascular or Microsurgical Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: Peri-interventional vasospasm (PIVS) is associated with high risk of delayed cerebral vasospasm (DCVS), delayed cerebral ischemia, and poor outcome after aneurysmal subarachnoid hemorrhage. However, the incidence rate associated with treatment of unruptured intracranial aneurysm (UIA) remains unclear. OBJECTIVE: To define the incidence and clinical significance of PIVS in UIA repair based on intraoperative/peri-interventional digital subtraction angiography. METHODS: A consecutive series of 205 patients who underwent UIA treatment by means of microsurgical clipping (n = 109) or endovascular coil embolization (n = 96) was assessed for the occurrence of PIVS. In all cases, PIVS was detected, measured, and classified using intraoperative/peri-interventional digital subtraction angiography. Severity of PIVS, association of PIVS with the development of DCVS, and neurological outcome were analyzed. RESULTS: Intraoperative PIVS was present in n = 14/109 (13%) patients with microsurgical clipping. Of these, caliber irregularities were mild (n = 10), moderate (n = 3), and severe (n = 1). In endovascularly treated patients, 6/96 (6%) developed PIVS, which were either mild (n = 3) or moderate (n = 3). Management in all cases included immediate intensive blood pressure management and application of topical papaverine or intra-arterial nimodipine immediately on detection of PIVS. No patient developed DCVS or lasting neurological deficits attributable to PIVS. CONCLUSION: This series revealed a relatively high overall incidence of PIVS (10%). However, no association of PIVS with the development of DCVS or poor outcome was found. In contrast to ruptured intracranial aneurysms, PIVS in unruptured intracranial aneurysms-if immediately and adequately addressed-seems to be benign and without sequelae for patient's functional outcome.

Lumen-oriented versus wall-oriented treatment strategies for intracranial aneurysms - A systematic review of suggested therapeutic concepts.

The development of new treatment strategies for intracranial aneurysms (IAs) has been and continues to be a major interest in neurovascular research. Initial treatment concepts were mainly based on a physical-mechanistic disease understanding for IA occlusion (lumen-oriented therapies). However, a growing body of literature indicates the important role of aneurysm wall biology (wall-oriented therapies) for complete IA obliteration. This systematic literature review identified studies that explored endovascular treatment strategies for aneurysm treatment in a preclinical setting. Of 5278 publications screened, 641 studies were included, categorized, and screened for eventual translation in a clinical trial. Lumen-oriented strategies included (1) enhanced intraluminal thrombus organization, (2) enhanced intraluminal packing, (3) bridging of the intraluminal space, and (4) other, alternative concepts. Wall-oriented strategies included (1) stimulation of proliferative response, (2) prevention of aneurysm wall cell injury, (3) inhibition of inflammation and oxidative stress, and (4) inhibition of extracellular matrix degradation. Overall, lumen-oriented strategies numerically still dominate over wall-oriented strategies. Among the plethora of suggested preclinical treatment strategies, only a small minority were translated into clinically applicable concepts (36 of 400 lumen-oriented and 6 of 241 wall-oriented). This systematic review provides a comprehensive overview that may provide a starting point for the development of new treatment strategies.

Restoring Segmental Spinal Alignment in Mini-Open Lateral Spinal Deformity Surgery-Determiners of Radiographic Outcome.

OBJECTIVE: Both under- and overcorrection are risk factors for junctional failure after deformity correction. This study investigates which factors determine the segmental radiographic outcome in mini-open lateral deformity surgery. METHODS: A single-center operative database was searched for patients undergoing multilevel mini-open lateral corrective surgery of degenerative spinal deformities. Preoperative and postoperative whole spine x-rays and computed tomography scans were compared for change in global and segmental alignment parameters. Linear regression analyses were performed to study the impact of surgical level, preoperative segmental sagittal Cobb angle, presence of bridging osteophytes, disc height, ankylosis of facet joints, and implantation site of the interbody device on postoperative increase in segmental lordosis, foraminal height, and foraminal width. RESULTS: A total of 49 patients were identified with a mean age of 68.7 years. At a mean, 4.2 segments were fused using a lateral approach, while the posterior stage comprised either minimally invasive surgery or open instrumentation. Upper instrumented vertebra was L2 (range T4-L3), and lower instrumented vertebra was L5 (range L4-pelvis) in most cases. Mean radiographic values pre- and postoperatively were as follows: C7 sagittal vertical axis +79.6 mm, +60 mm; lumbar lordosis 32.9°, 41.6°; pelvic tilt 21.1°, 21.8°; global coronal Cobb 16.3°, 10.8°; increase in segmental sagittal Cobb angle was significantly and inversely correlated with preoperative sagittal Cobb and positively correlated with preoperative coronal Cobb angle. No other variable showed significant correlations. Preoperative foraminal width and height showed significant and inverse correlation with change in postoperative foraminal width and height. CONCLUSION: Segmental sagittal correction is significantly influenced by preoperative loss of lordosis and coronal Cobb angle. Neither presence of osteophytes nor ankylosed facet joints, disc height, or implantation site of the interbody device had an influence on sagittal alignment goals. Only preoperative foraminal dimensions impact inversely the degree of foraminal decompression; no other factor investigated showed significant impact. CLINICAL RELEVANCE: Only preoperative lordosis and coronal Cobb angle influence sagittal correction.

Using a Cell-Tracer Injection to Investigate the Origin of Neointima-Forming Cells in a Rat Saccular Side Wall Model.

Microsurgical clipping creates a subsequent barrier of blood flow into intracranial aneurysms, whereas endovascular treatment relies on neointima and thrombus formation. The source of endothelial cells covering the endoluminal layer of the neointima remains unclear. Therefore, the aim of the present study was to investigate the origin of neointima-forming cells after cell-tracer injection in the already well-established Helsinki rat microsurgical sidewall aneurysm model. Sidewall aneurysms were created by suturing decellularized or vital arterial pouches end-to-side to the aorta in male Lewis rats. Before arteriotomy with aneurysm suture, a cell-tracer injection containing CM-Dil dye was performed into the clamped aorta to label endothelial cells in the adjacent vessel and track their proliferation during follow-up (FU). Treatment followed by coiling (n = 16) or stenting (n = 15). At FU (7 days or 21 days), all rats underwent fluorescence angiography, followed by aneurysm harvesting and macroscopic and histological evaluation with immunohistological cell counts for specific regions of interest. None of the 31 aneurysms had ruptured upon follow-up. Four animals died prematurely. Macroscopically residual perfusion was observed in 75.0% coiled and 7.0% of stented rats. The amount of cell-tracer-positive cells was significantly elevated in decellularized stented compared to coiled aneurysms with respect to thrombus on day 7 (p = 0.01) and neointima on day 21 (p = 0.04). No significant differences were found in thrombus or neointima in vital aneurysms. These findings confirm worse healing patterns in coiled compared to stented aneurysms. Neointima formation seems particularly dependent on the parent artery in decellularized aneurysms, whereas it is supported by the recruitment from aneurysm wall cells in vital cell-rich walls. In terms of translation, stent treatment might be more appropriate for highly degenerated aneurysms, whereas coiling alone might be adequate for aneurysms with mostly healthy vessel walls.

Tocilizumab Reduces Vasospasms, Neuronal Cell Death, and Microclot Formation in a Rabbit Model of Subarachnoid Hemorrhage.

Early brain injury (EBI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia (DCI) are common complications of subarachnoid hemorrhage (SAH). Inflammatory processes in the cerebrospinal fluid (CSF) are one of the causes for such complications. Our aim to study the effects of an IL-6 receptor antagonist (Tocilizumab) examines the occurrence of DCVS, neuronal cell death, and microclot formation in an acute SAH rabbit model. Twenty-nine New Zealand white rabbits were randomized into one of three groups as the SAH, SAH + Tocilizumab, and sham groups. In SAH groups, hemorrhage was induced by extracranial-intracranial arterial blood shunting from the subclavian artery into the cisterna magna under intracranial pressure (ICP) monitoring. In the second group, Tocilizumab was given once intravenously 1 h after SAH induction. Digital subtraction angiography was performed, and CSF and blood were sampled before and after (day 3) SAH induction. IL-6 plasma and CSF levels were measured. TUNEL, FJB, NeuN, and caspase-3 immunostaining were used to assess cell apoptosis, neurodegeneration, and neuronal cell death, respectively. Microclot formation was detected by fibrinogen immunostaining. Between baseline and follow-up, there was a significant reduction of angiographic DCVS (p < 0.0001) in the Tocilizumab compared with the SAH group. Tocilizumab treatment resulted in decreased neuronal cell death in the hippocampus (p = 0.006), basal cortex (p = 0.001), and decreased microclot formation (p = 0.02). Tocilizumab reduced DCVS, neuronal cell death, and microclot formation in a rabbit SAH model, and could be a potential treatment to prevent DCVS and DCI in SAH patients.

Preclinical Intracranial Aneurysm Models: A Systematic Review.

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.

Saccular Aneurysm Models Featuring Growth and Rupture: A Systematic Review.

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.