Acute ischemic stroke caused by large vessel occlusions is being increasingly treated with neurovascular interventions. The hemodynamics within the collateral system of the circle of Willis (CoW) hemodynamics play a fundamental role in therapy success. However, transient in vivo data on pathological collateral flow during large vessel occlusions are not available. Moreover, there are no flow models that accurately simulate the hemodynamic conditions in the CoW during large vessel occlusions. We used a circulatory loop to generate highly reproducible cerebrovascular-like flows and pressures and used non-invasive flow visualization and high-resolution flow and pressure measurements to acquire detailed, time-dependent hemodynamics inside an anatomical phantom of the CoW. After calibrating a physiological reference case, we induced occlusions in the 1. middle cerebral artery, 2. terminal carotid artery, and 3. basilar artery; and measured the left posterior communicating artery flow. Mean arterial pressure and pulse pressure remained unchanged in the different occlusion cases compared to the physiological reference case, while total cerebral flow decreased by up to 19%. In all three occlusion cases, reversed flow was found in the left posterior communicating artery compared to the reference case with different flow magnitudes and pulsatility index values. The experimental results were compared with clinical findings, demonstrating the capability of this realistic cerebrovascular flow setup. This novel cerebrovascular flow setup opens the possibility for investigating different topics of neurovascular interventions under various clinical conditions in controlled preclinical laboratory studies.

We investigated the reduction in regional brain volume and cerebral blood flow (CBF) with aging and explored potential sex differences in healthy brains. Three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI), time-of-flight magnetic resonance angiography, and four-dimensional (4D) flow MRI were performed on 129 healthy volunteers aged 22-92 years. The brains of healthy volunteers were segmented into 21 subregions using 3D T1-weighted MRI and CBFs in 16 major intracranial arteries were measured using 4D flow MRI. The cortical gray matter volume decreased linearly with aging, whereas the cerebral white matter volume increased until the 40s and then decreased, and the subcortical gray matter volume changed little with aging. The cortical gray matter volume was significantly associated with the total CBF of the major intracranial arteries distal to the circle of Willis; however, the cerebral white matter and subcortical gray matter volumes were not. Generally, women have higher total CBF than men, particularly in their 40s and younger, despite the smaller intracranial volume and smaller diameters of intracranial arteries than men. This may contribute to the higher incidence of subarachnoid hemorrhage due to cerebral aneurysms and migraine in women.

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BACKGROUND: To evaluate the impact of anatomical variations in the Circle of Willis (CoW) on immediate neurological events (INEs) after carotid endarterectomy (CEA) without shunting in patients with contralateral carotid occlusion (CCO).
METHODS: Single-center retrospective study. Patient\'s demographic and clinical outcomes data were prospectively collected. CoW segments were reviewed retrospectively. Between January 2013 and May 2018, 2090 patients underwent CEA under general anesthesia, CCO was found in 113 (5.4%) patients. CoW segments were classified as normal, hypoplastic (diameter ˂0.8 mm), or absent based on computed tomography angiography. We studied the CoW segments as 2 collateral networks connecting the basilar artery and the ipsilateral middle cerebral artery: a short semicircle (first segment of the ipsilateral posterior cerebral artery [P1] and posterior communicating artery [Pcom] segment) and a long semicircle (contralateral P1, Pcom, and both first segments of the anterior cerebri artery (A1) anterior communicating artery (Acom)). INE was defined as any transient ischemic attack or stroke diagnosed immediately after the procedure.
RESULTS: Out of the 113 patients, 46 underwent endarterectomy with shunting. We further excluded 16 patients from the assessment of the CoW due to unavailability or inadequate quality of computed tomography angiography. Of the 113 patients, 2 had strokes, 1 with shunting that occurred hrs after surgery. Besides the other stroke case, 4 INE were observed, all without the use of a shunt. Of the 51 patients with CoW assessment, 10 (19.6%) had a complete CoW, while 21 (41.2%) patients had only 1 semicircle intact (10 short and 11 long intact semicircles), and none of these patients experienced an INE. A total of 20 (39%) patients had both the long and short semicircles incomplete, of which 4 (7.8%) cases had an INE. In all INE cases, at least 1 of the Pcom was absent or hypoplastic. The absence of both Pcom was a strong predictor of incident INE [odds ratio = 11.10 (confidence interval: 1.04-118.60)] for INE.
CONCLUSIONS: Patients with CCO and insufficient CoW collateral flow support are at an increased risk of INE, including stroke, in the absence of shunt protection during CEA cross-clamping. Shunting should always be considered when the collateral flow between the ipsilateral middle cerebral artery and the basilar artery is compromised in CCO patients.

BACKGROUND: The fetal-type posterior cerebral artery (PCA) is defined as a variant anatomy in which the posterior communicating artery (PCOM) is larger than the hypoplastic or aplastic P1 segment of the PCA. The authors present the novel case of a patient with a duplicated right PCA in parallel with fetal-type and conventional PCAs supplying adjacent components of the PCA cerebral territory.
METHODS: A 59-year-old woman presented with a modified Fisher Scale score 4 subarachnoid hemorrhage. A right irregular PCOM aneurysm that measured 9.5 mm × 4.5 mm × 4.5 mm arose from the base of a variant branch supplying a portion of the PCA, rather than a conventional PCOM, and was found on digital subtraction angiography. Following endovascular coil embolization, the patient was discharged home.
CONCLUSIONS: The fetal-type variant has implications for thromboembolic events. If an embolism occludes the anterior circulation in a patient with a fetal-type PCA, it may result in an infarct in the PCA territory. Awareness of cerebral arterial anatomy, including an atypical collateral supply, informs a treating team\'s latitude in tolerance of which sites must be preserved and which can be safely sacrificed. https://thejns.org/doi/10.3171/CASE23735.

Vascular smooth muscle cells (VSMCs) envelop vertebrate brain arteries and play a crucial role in regulating cerebral blood flow and neurovascular coupling. The dedifferentiation of VSMCs is implicated in cerebrovascular disease and neurodegeneration. Despite its importance, the process of VSMC differentiation on brain arteries during development remains inadequately characterized. Understanding this process could aid in reprogramming and regenerating dedifferentiated VSMCs in cerebrovascular diseases. In this study, we investigated VSMC differentiation on zebrafish circle of Willis (CoW), comprising major arteries that supply blood to the vertebrate brain. We observed that arterial specification of CoW endothelial cells (ECs) occurs after their migration from cranial venous plexus to form CoW arteries. Subsequently, acta2+ VSMCs differentiate from pdgfrb+ mural cell progenitors after they were recruited to CoW arteries. The progression of VSMC differentiation exhibits a spatiotemporal pattern, advancing from anterior to posterior CoW arteries. Analysis of blood flow suggests that earlier VSMC differentiation in anterior CoW arteries correlates with higher red blood cell velocity and wall shear stress. Furthermore, pulsatile flow induces differentiation of human brain PDGFRB+ mural cells into VSMCs, and blood flow is required for VSMC differentiation on zebrafish CoW arteries. Consistently, flow-responsive transcription factor klf2a is activated in ECs of CoW arteries prior to VSMC differentiation, and klf2a knockdown delays VSMC differentiation on anterior CoW arteries. In summary, our findings highlight blood flow activation of endothelial klf2a as a mechanism regulating initial VSMC differentiation on vertebrate brain arteries.

UNASSIGNED: Circulus arteriosus cerebri (CAC), responsible for supplying blood to the brain, presents anatomical variations that have been associated with both haemorrhagic and ischemic strokes. Therefore, it is crucial to conduct comprehensive investigations and comparisons of the diverse variant components of the CAC, published in various journals, and analyze them to identify individuals at risk of cerebrovascular pathologies, thereby ensuring enhanced and timely treatment.
UNASSIGNED: A scoping review according to the five-stage protocol by Arksey and O\'Malley was performed between February and June 2023. Seven hundred and seventy-seven records were initially identified, and a total of 51 studies were finally included.
UNASSIGNED: This scoping review focuses on the anatomical variations of the CAC and their clinical implications on cerebrovascular disease and includes more original articles than review s. Consistent with previous findings, most of the records included small populations or samples, while only three records reported larger populations. Surprisingly, the populations enclosed in the included records consisted of autopsied cadaveric specimens more than living subjects. Finally, the qualitative analysis highlighted three main themes concerning the relationship between the normal CAC morphology and the cerebrovascular disease onset as well as the variant CAC morphology and its main features that might be also involved in these diseases. Finally, techniques that can be used to measure CAC have also been assessed.
UNASSIGNED: Variations in the CAC, more common in the posterior part, with genetic and environmental factors influencing these variations impact cerebrovascular disorders. Understanding variants components of CAC can aid in improving brain surgeries and post-stroke care.

Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.