The guardian of intracranial vessels: Why the pericyte?

Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused by plaque formation. This condition leads to reduced blood flow to the brain, resulting in cerebral ischemia and hypoxia. Ischemic stroke (IS) resulting from ICAS poses a significant global public health challenge, especially among East Asian populations. However, the underlying causes of the notable variations in prevalence among diverse populations, as well as the most effective strategies for preventing and treating the rupture and blockage of intracranial plaques, remain incompletely comprehended. Rupture of plaques, bleeding, and thrombosis serve as precipitating factors in the pathogenesis of luminal obstruction in intracranial arteries. Pericytes play a crucial role in the structure and function of blood vessels and face significant challenges in regulating the Vasa Vasorum (VV)and preventing intraplaque hemorrhage (IPH). This review aims to explore innovative therapeutic strategies that target the pathophysiological mechanisms of vulnerable plaques by modulating pericyte biological function. It also discusses the potential applications of pericytes in central nervous system (CNS) diseases and their prospects as a therapeutic intervention in the field of biological tissue engineering regeneration.

Global intracranial arterial tortuosity is associated with intracranial atherosclerotic burden.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

Numerical flow experiment for assessing predictors for cerebrovascular accidents in patients with PHACES syndrome.

There is an increased risk of cerebrovascular accidents (CVA) in individuals with PHACES, yet the precise causes are not well understood. In this analysis, we aimed to examine the role of arteriopathy in PHACES syndrome as a potential contributor to CVA. We analyzed clinical and radiological data from 282 patients with suspected PHACES syndrome. We analyzed clinical features, including the presence of infantile hemangioma and radiological features based on magnetic resonance angiography or computed tomography angiography, in individuals with PHACES syndrome according to the Garzon criteria. To analyze intravascular blood flow, we conducted a simulation based on the Fluid-Structure Interaction (FSI) method, utilizing radiological data. The collected data underwent statistical analysis. Twenty patients with PHACES syndrome were included. CVAs were noted in 6 cases. Hypoplasia (p = 0.03), severe tortuosity (p < 0.01), absence of at least one main cerebral artery (p < 0.01), and presence of persistent arteries (p = 0.01) were associated with CVAs, with severe tortuosity being the strongest predictor. The in-silico analysis showed that the combination of hypoplasia and severe tortuosity resulted in a strongly thrombogenic environment. Severe tortuosity, combined with hypoplasia, is sufficient to create a hemodynamic environment conducive to thrombus formation and should be considered high-risk for cerebrovascular accidents (CVAs) in PHACES patients.

Pathology-based brain arterial disease phenotypes and their radiographic correlates.

INTRODUCTION: Brain arterial diseases, including atherosclerosis, vasculitis, and dissections, are major contributors to cerebrovascular morbidity and mortality worldwide. These diseases not only increase the risk of stroke but also play a significant role in neurodegeneration and dementia. Clear and unambiguous terminology and classification of brain arterial disease phenotypes is crucial for research and clinical practice. MATERIAL AND METHODS: This review aims to summarize and harmonize the terminology used for brain large and small arterial phenotypes based on pathology studies and relate them to imaging phenotypes used in medical research and clinical practice. CONCLUSIONS AND RESULTS: Arteriosclerosis refers to hardening of the arteries but does not specify the underlying etiology. Specific terms such as atherosclerosis, calcification, or non-atherosclerotic fibroplasia are preferred. Atherosclerosis is defined pathologically by an atheroma. Other brain arterial pathologies occur and should be distinguished from atherosclerosis given therapeutic implications. On brain imaging, intracranial arterial luminal stenosis is usually attributed to atherosclerosis in the presence of atherosclerotic risk factors but advanced high-resolution arterial wall imaging has the potential to more accurately identify the underlying pathology. Regarding small vessel disease, arteriosclerosis is ambiguous and arteriolosclerosis is often used to denote the involvement of arterioles rather than arteries. Lipohyalinosis is sometimes used synonymously with arteriolosclerosis, but less accurately describes this common small vessel thickening which uncommonly shows lipid. Specific measures of small vessel wall thickness, the relationship to the lumen as well as changes in the layer composition might convey objective, measurable data regarding the status of brain small vessels.

Changes in arterial myocyte excitability induced by subarachnoid hemorrhage in a rat model.

Aneurismal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by the rupture of the cerebral arteries and the extravasation of blood to the subarachnoid space and is accompanied by severe comorbidities. Secondarily associated vasospasm is one of the main side effects after hydrocephalus and possible rebleeding. Here, we analyze the alterations in function in the arteries of a rat model of SAH. For this, autologous blood was injected into the cisterna magna. We performed electrophysiological, microfluorimetric, and molecular biology experiments at different times after SAH to determine the functional and molecular changes induced by the hemorrhage. Our results confirmed that in SAH animals, arterial myocytes were depolarized on days 5 and 7, had higher [Ca2+]i on baseline, peaks and plateaus, and were more excitable at low levels of depolarization on day 7, than in the control and sham animals. Microarray analysis showed that, on day 7, the sets of genes related to voltage-dependent Ca2+ channels and K+ dynamics in SAH animals decreased, while the voltage-independent Ca2+ dynamics genes were over-represented. In conclusion, after SAH, several mechanisms involved in arterial reactivity were altered in our animal model, suggesting that there is no unique cause of vasospasm and alterations in several signaling pathways are involved in its development.

An autopsy case of intravascular large B-cell lymphoma showing a rapid transition to embolic strokes with occlusion of the major cerebral arteries.

Intravascular large B-cell lymphoma can induce central nervous system manifestations, including strokes, due to small-vessel occlusion caused by lymphoma cells. However, involvement in large-sized vessels is rare. Here, we present an unusual autopsy case of an 88-year-old man showing a rapid transition from multiple strokes due to small vessel occlusion, typical of intravascular lymphoma, to progressive embolic strokes caused by the occlusion of major cerebral arteries. Magnetic resonance angiography demonstrated the major cerebral arteries associated with those multiple progressive strokes, including the right posterior cerebral artery, left anterior cerebral artery, and right middle cerebral artery, but the detectability was poor. A random skin biopsy at the abdomen confirmed the diagnosis of intravascular large B-cell lymphoma. The patient died 106 days after hospitalization despite intensive treatment. An autopsy revealed broad liquefactive necrosis in the area governed by the major cerebral arteries and multiple small infarctions caused by intravascular lymphoma cells in the small-sized vessels. In addition, the major cerebral arteries showed multiple thromboembolism with partial organization and clusters of intravascular lymphoma cells. Notably, those cells were shown aggregated and attached along the vascular wall of the basilar artery, which might have caused focal hypercoagulation in the near vessels. This aggregation might have disseminated widely in the other major cerebral arteries. Moreover, the cluster of intravascular lymphoma cells in the basilar artery was positive for tumor necrosis factor α, and similar histopathology findings were observed in the splenic veins. However, the pathogenesis of this rare phenomenon involving these cells remains unknown. From a clinical perspective, we should consider the possibility that intravascular lymphoma cells may provoke similar progressive embolic strokes.

Visualization of the lenticulostriate arteries, long insular arteries, and long medullary arteries on intra-arterial computed tomography angiography with ultrahigh resolution in patients with glioma.

PURPOSE: The anatomical association between the lesion and the perforating arteries supplying the pyramidal tract in insulo-opercular glioma resection should be evaluated. This study reported a novel method combining the intra-arterial administration of contrast medium and ultrahigh-resolution computed tomography angiography (UHR-IA-CTA) for visualizing the lenticulostriate arteries (LSAs), long insular arteries (LIAs), and long medullary arteries (LMAs) that supply the pyramidal tract in two patients with insulo-opercular glioma. METHODS: This method was performed by introducing a catheter to the cervical segment of the internal carotid artery. The infusion rate was set at 3 mL/s for 3 s, and the delay time from injection to scanning was determined based on the time-to-peak on angiography. On 2- and 20-mm-thick UHR-IA-CTA slab images and fusion with magnetic resonance images, the anatomical associations between the perforating arteries and the tumor and pyramidal tract were evaluated. RESULTS: This novel method clearly showed the relationship between the perforators that supply the pyramidal tract and tumor. It showed that LIAs and LMAs were far from the lesion but that the proximal LSAs were involved in both cases. Based on these results, subtotal resection was achieved without complications caused by injury of perforators. CONCLUSION: UHR-IA-CTA can be used to visualize the LSAs, LIAs, and LMAs clearly and provide useful preoperative information for insulo-opercular glioma resection.

CT hyperdense cerebral artery sign reflects distinct proteomic composition in acute ischemic stroke thrombus.

BACKGROUND: Hyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior studies have correlated HCAS with histopathological composition of cerebral thrombus, it is unknown whether and to what extent HCAS is also associated with distinct clot protein composition. METHODS: Thromboembolic material from 24 patients with AIS were retrieved via mechanical thrombectomy and evaluated with mass spectrometry in order to characterize their proteomic composition. Presence (+) or absence (-) of HCAS on preintervention non-contrast head CT was then determined and correlated with thrombus protein signature with abundance of individual proteins calculated as a function HCAS status. RESULTS: 24 clots with 1797 distinct proteins in total were identified. 14 patients were HCAS(+) and 10 were HCAS(-). HCAS(+) were most significantly differentially abundant in actin cytoskeletal protein (P=0.002, Z=2.82), bleomycin hydrolase (P=0.007, Z=2.44), arachidonate 12-lipoxygenase (P=0.004, Z=2.60), and lysophospholipase D (P=0.007, Z=2.44), among other proteins; HCAS(-) clots were differentially enriched in soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (P=0.0009, Z=3.11), tyrosine-protein kinase Fyn (P=0.002, Z=2.84), and several complement proteins (P<0.05, Z>1.71 for all), among numerous other proteins. Additionally, HCAS(-) thrombi were enriched in biological processes involved with plasma lipoprotein and protein-lipid remodeling/assembling, and lipoprotein metabolic processes (P<0.001), as well as cellular components including mitochondria (P<0.001). CONCLUSIONS: HCAS is reflective of distinct proteomic composition in AIS thrombus. These findings suggest that imaging can be used to identify mechanisms of clot formation or maintenance at the protein level, and might inform future research on thrombus biology and imaging characterization.

Automated in-depth cerebral arterial labelling using cerebrovascular vasculature reframing and deep neural networks.

Identifying the cerebral arterial branches is essential for undertaking a computational approach to cerebrovascular imaging. However, the complexity and inter-individual differences involved in this process have not been thoroughly studied. We used machine learning to examine the anatomical profile of the cerebral arterial tree. The method is less sensitive to inter-subject and cohort-wise anatomical variations and exhibits robust performance with an unprecedented in-depth vessel range. We applied machine learning algorithms to disease-free healthy control subjects (n = 42), patients with stroke with intracranial atherosclerosis (ICAS) (n = 46), and patients with stroke mixed with the existing controls (n = 69). We trained and tested 70% and 30% of each study cohort, respectively, incorporating spatial coordinates and geometric vessel feature vectors. Cerebral arterial images were analyzed based on the 'segmentation-stacking' method using magnetic resonance angiography. We precisely classified the cerebral arteries across the exhaustive scope of vessel components using advanced geometric characterization, redefinition of vessel unit conception, and post-processing algorithms. We verified that the neural network ensemble, with multiple joint models as the combined predictor, classified all vessel component types independent of inter-subject variations in cerebral arterial anatomy. The validity of the categorization performance of the model was tested, considering the control, ICAS, and control-blended stroke cohorts, using the area under the receiver operating characteristic (ROC) curve and precision-recall curve. The classification accuracy rarely fell outside each image's 90-99% scope, independent of cohort-dependent cerebrovascular structural variations. The classification ensemble was calibrated with high overall area rates under the ROC curve of 0.99-1.00 [0.97-1.00] in the test set across various study cohorts. Identifying an all-inclusive range of vessel components across controls, ICAS, and stroke patients, the accuracy rates of the prediction were: internal carotid arteries, 91-100%; middle cerebral arteries, 82-98%; anterior cerebral arteries, 88-100%; posterior cerebral arteries, 87-100%; and collections of superior, anterior inferior, and posterior inferior cerebellar arteries, 90-99% in the chunk-level classification. Using a voting algorithm on the queued classified vessel factors and anatomically post-processing the automatically classified results intensified quantitative prediction performance. We employed stochastic clustering and deep neural network ensembles. Ma-chine intelligence-assisted prediction of vessel structure allowed us to personalize quantitative predictions of various types of cerebral arterial structures, contributing to precise and efficient decisions regarding the cerebrovascular disease.

Standard clinical computed tomography fails to precisely visualise presence, course and branching points of deep cerebral perforators.

BACKGROUND: Standard computed tomography (CT) images have earned a well-established position in neuroimaging. Despite that, CT is somehow limited by its resolution, which does not enable to distinctively visualise structures smaller than 300 µm in diameter. Perforating arteries, most of which measure 100-400 µm in diameter, supply important subcortical structures (thalamus, basal ganglia, internal capsule). Consequently, pathologies affecting these vessels (e.g. lacunar strokes) can have a devastating clinical outcome. The aim of our study was to assess standard CT's ability to visualise perforators and compare it with microscopic and micro-CT pictures. MATERIALS AND METHODS: We have obtained 6 brainstem and 17 basal ganglia specimens. We infused them with barium sulphate contrast medium administered into either vertebral or internal cerebral artery. After that, the specimens were fixed in formalin and subsequently a series of CT, micro-CT and microscopic examinations were performed. RESULTS: The median number of visualised perforators in brainstem and basal ganglia specimens was 8 and 3, respectively for CT and 18 and 7 for micro-CT (p < 0.05). Standard CT failed to clearly visualise branching points and vessels smaller than 0.25-0.5 mm (1-2 voxels) in diameter. Parallel vessels, like lenticulostriate arteries could not be differentiated in standard CT due to their proximity being smaller that the resolution. CONCLUSIONS: Basing on our results, we infer that CT is a poor modality for imaging of the perforators, presenting both quantitative and qualitative flaws in contrast with micro-CT.

Structural and Functional Characteristics of Cerebral Arteries as an Explanation for Clinical Syndromes Limited to the Brain.

Vascular disease affects many different arterial beds throughout the body. Yet the brain is susceptible to several vascular disorders that either are not found in other parts of the body or when found are much less likely to cause clinical syndromes in other organs. This specific vulnerability of the brain may be explained by structural and functional differences between the vessels of the brain and those of vessels in other parts of the body. In this review, we focus on how cerebrovascular anatomy and physiology may make the brain and its vessels more susceptible to unique vascular pathologies. To highlight these differences, we use our knowledge of five diseases and syndromes that most commonly manifest in the intracranial vasculature. For each, we identify characteristics of the intracranial arteries that make them susceptible to these diseases, while noting areas of uncertainty requiring further research.

Aphasia with No Apparent Paralysis in Progressive Stroke of the Anterior Choroidal Artery.

Some anterior choroidal artery (AChA) infarctions in the posterior limbs of the internal capsule (plIC) have been reported to cause aphasia, typically with apparent paralysis. We herein report an 84-year-old woman with AChA infarction. Although her dysarthria remained mild with no apparent paralysis, we overlooked progression to branch atheromatous disease-related infarct with exacerbation of her anomia, which delayed the initiation of more intense therapy. Even in AChA infarction, especially when the lesion is located mainly in the anterior part of the plIC, as in our case, it is possible to encounter progressive stroke predominantly with aphasia.

Vessel Wall Imaging of Intracranial Arteries: Fundamentals and Clinical Applications.

With the increasing use of 3-tesla MRI scanners and the development of applicable sequences, it has become possible to achieve high-resolution, good contrast imaging, which has enabled the imaging of the walls of small-diameter intracranial arteries. In recent years, the usefulness of vessel wall imaging has been reported for numerous intracranial arterial diseases, such as for the detection of vulnerable plaque in atherosclerosis, diagnosis of cerebral arterial dissection, prediction of the rupture of cerebral aneurysms, and status of moyamoya disease and cerebral vasculitis. In this review, we introduce the histological characteristics of the intracranial artery, discuss intracranial vessel wall imaging methods, and review the findings of vessel wall imaging for various major intracranial arterial diseases.

Characterization of non-stenotic plaques in intracranial arteries with multi-contrast, multi-planar vessel wall image analysis.

OBJECTIVES: Non-stenotic plaques have been observed in intracranial arteries but are less understood compared to those in coronary and carotid arteries. We sought to compare plaque distribution and morphology between stenotic and non-stenotic intracranial plaques with MR vessel wall imaging (VWI) and quantitative image analysis. MATERIALS AND METHODS: Twenty-four patients with intracranial arterial stenosis or luminal irregularity on clinical imaging were scanned with a multi-contrast VWI protocol. Plaques were detected as focal wall thickening on co-registered multiplanar reformats of multi-contrast VWI, with assessment of the location and morphology. TOF-MRA was independently reviewed for any appreciable stenosis using the WAISD criteria. RESULTS: Across 504 arterial segments, a total of 80 plaques were detected, including 23 (29%) with stenosis on TOF-MRA, 56 (70%) without, and 1 (1%) not covered by TOF-MRA. Plaques involving the ICA were more likely to be non-stenotic than those involving other segments (80% versus 55%, p = 0.030) whereas the basilar artery (40%) and PCA (33%) had the lowest proportions of non-stenotic plaques. Maximum wall thickness, indicative of plaque burden, correlated poorly with degree of stenosis (p = 0.10) and overlapped substantially between stenotic and non-stenotic plaques (1.9 [1.5, 2.4] versus 2.0 [1.5, 2.2] mm, p = 0.074). CONCLUSIONS: Intracranial plaques without appreciable stenosis on TOF-MRA represent a large proportion of lesions throughout arterial segments but disproportionately affect the ICA. Morphological characterization of plaques with and without stenosis shows that luminal stenosis is a poor indicator of the underlying burden of intracranial atherosclerosis.

Changes of Atherosclerotic Plaque in Cerebral Artery Stenosis According to High-Resolution MR Imaging.

Atherosclerosis can affect multiple arteries, and result in stroke and heart disease. Clinical and conventional imaging is insufficient to predict the progression of atherosclerosis. This study investigates risk factors that rely on high-resolution magnetic resonance imaging (HR-MRI). Patients with cerebral artery stenosis who had undergone HR-MRI at least twice were included. The demographics, risk factors, and proportion of patients with cerebral artery stenosis were investigated. The association between atherosclerotic plaque characteristics and the progression or regression of artery stenosis was also analyzed. A total of 42 patients were analyzed, with a median follow-up of 16.88 ± 12.53 months. The mean age of all subjects was 63.1 ± 9.15 years, and 83.3% of them were male. The incidences of stenosis of the basilar, proximal internal carotid, and middle cerebral arteries were 21.4%, 61.9%, and 16.7%, respectively. Intraplaque hemorrhage (IPH) was detected in 20 (47.6%) patients. Multivariate analysis showed that age (odds ratio (OR), 0.87; p = 0.014), smoking (OR, 0.11; p = 0.033), and IPH regression (OR, 10.13; p = 0.027) were associated with stenosis regression. The progression of IPH (OR, 115.80; p = 0.007) was associated with stenosis progression. Results suggest that IPH on HR-MRI is associated with changes in cerebral atherosclerotic stenosis.

Pulsatility Index in the Basal Ganglia Arteries Increases with Age in Elderly with and without Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease contributes to stroke and cognitive impairment and interacts with Alzheimer disease pathology. Because of the small dimensions of the affected vessels, in vivo characterization of blood flow properties is challenging but important to unravel the underlying mechanisms of the disease. MATERIALS AND METHODS: A 2D phase-contrast sequence at 7T MR imaging was used to assess blood flow velocity and the pulsatility index of the perforating basal ganglia arteries. We included patients with cerebral amyloid angiopathy (n = 8; identified through the modified Boston criteria), hypertensive arteriopathy (n = 12; identified through the presence of strictly deep or mixed cerebral microbleeds), and age- and sex-matched controls (n = 28; no cerebral microbleeds). RESULTS: Older age was related to a greater pulsatility index, irrespective of cerebral small vessel disease. In hypertensive arteriopathy, there was an association between lower blood flow velocity of the basal ganglia and the presence of peri-basal ganglia WM hyperintensities. CONCLUSIONS: Our results suggest that age might be the driving factor for altered cerebral small vessel hemodynamics. Furthermore, this study puts cerebral small vessel disease downstream pathologies in the basal ganglia region in relation to blood flow characteristics of the basal ganglia microvasculature.

Prevalence of anatomical variants of the Willis polygon in cadavers undergoing medico-legal necropsy / Prevalencia de variantes anatómicas del Polígono de Willis en cadáveres sometidos a necropsia medicolegal

The primary function of the circle of Willis is to provide collateral blood flow between the anterior and posterior arterial systems of the brain. Its configuration can vary considering its vascular structures, this being considered an anatomical variant. Our study aims to determine the prevalence of these, discriminated by sex in corpses subjected to medicolegal autopsy at the National Institute of Legal Medicine and Forensic Sciences in 2019, in Cali-Colombia. Retrospective observational descriptive study, of photographic records, inspection records and expert reports, where variables of age, sex, anatomical variants, compromised vascular structures are differentiated. Univariate and bivariate analyzes were performed. The population consisted of 194 cases, with a median age of 33 years (interquartile range between 23-45). 24.4% corresponded to the male sex. A prevalence of 25.3% of cases with non-classic polygon was observed. The most frequent anatomical variant was hypoplasia 14.9%. The vascular structure that presented the most anatomical variants was the posterior communicating artery with 17%.

La función principal del polígono de Willis es proporcionar flujo sanguíneo colateral entre los sistemas arteriales anterior y posterior del cerebro. Su configuración puede variar teniendo en cuenta sus estructuras vasculares, considerándose esto una variante anatómica. En este estudio analizamos la prevalencia de las variaciones, discriminada por sexo en cadáveres sometidos a necropsia medicolegal en el Instituto Nacional de Medicina Legal y Ciencias Forenses en el año 2019, en Cali-Colombia. Estudio descriptivo observacional retrospectivo, de registros fotográficos, actas de inspección e informes periciales, donde se diferencia variables de edad, sexo, variantes anatómicas, estructuras vasculares comprometidas. Se realizaron análisis uni y bivariados. La población estuvo conformada por 194 casos, con una mediana de edad de 33 años (rango intercuartil entre 23-45). El 24.4% correspondieron al sexo masculino. Un 25,3% de casosse encontró un polígono no clásico. La variante anatómica más frecuente fue la hipoplasia 14.9%. La estructura vascular que más variantes anatómicas presentó fue la arteria comunicante posterior con un 17%.

Rs12976445 polymorphism is associated with the risk of post-SAH re-bleeding by modulating the expression of microRNA-125 and ET-1.

This study aimed to study the association between rs12976445 polymorphism and the incidence of IA re-bleeding. Genotype and allele frequency analysis was performed to study the association between rs12976445 polymorphism and the risk of IA re-bleeding. Western blot, ELISA and real-time RT-PCR were conducted to measure the relative expression of miR-125a, ET1 mRNA and ET1 protein. Computational analysis and luciferase assays were utilized to investigate the association between the expression of miR-125a and ET1 mRNA. No significant differences were observed between IA patients with or without symptoms of re-bleeding. Subsequent analyses indicated that the T allele was significantly associated with the reduced risk of IA re-bleeding. In patients carrying the CC genotype, miR-125a level was up-regulated while ET1 mRNA/protein levels were reduced compared with those in patients carrying the CT or TT genotype. And ET1 mRNA was identified as a virtual target gene of miR-125a with a potential miR-125a binding site located on its 3'UTR. Accordingly, the ET mRNA/protein levels could be suppressed by the transfection of miR-125a precursors, but the transfection of ET1 siRNA exhibited no effect on the expression of miR-125a. Therefore, an increased level of miR-125a can lead to the increased risk of IA re-bleeding. Since miR-125a level is higher in CC-genotyped patients, it can be concluded that the presence of T allele in the rs12976445 polymorphism is associated with a lower risk of IA re-bleeding, and miR-125a may be used as a novel diagnostic and therapeutic target for IA rupture.

Structural Changes of Intra and Extracranial Artery Dissection: a Study of High-Resolution Magnetic Resonance Imaging.

OBJECTIVES: The prognosis of a cerebral artery dissection is known to be benign, but the structural changes of vessel wall at follow-up are not well known. The natural course of an intracranial and extracranial artery dissection may differ due to structural differences. We aimed to figure out how stenosis and other wall features change, according to the dissection location. MATERIALS AND METHODS: We retrospectively enrolled patients who suffered an ischemic stroke or transient ischemic attack due to a dissection and who had undergone both initial and follow-up high-resolution magnetic resonance imaging (HRMRI). Patients were dichotomized to intracranial or extracranial dissection group. The clinical and HRMRI characteristics of two groups were compared. Factors associated with stenosis changes were also investigated. RESULTS: A total of 57 patients (intracranial, n = 43; and extracranial, n = 14) were enrolled. The mean age (45.6 vs. 32.2, p < 0.001) was higher and hypertension (37.2% vs. 7.1%, p = 0.04) was more frequent in the intracranial dissection group. In HRMRI analysis, stenosis improvement (27.9% vs. 85.7%, p < 0.001) were more frequent whereas residual wall enhancement (86.0% vs. 46.2%, p = 0.006) and intramural hematoma (62.8% vs. 21.4%, p = 0.007) were less frequent in the extracranial dissection group. Multivariate analysis indicated that extracranial location was the only independent factor (odds ratio 8.98, 95 % confidence interval 1.45-55.65; p = 0.02) associated with stenosis improvement. CONCLUSIONS: Younger age, stenosis improvement, disappearance of wall enhancement and intramural hematoma were more frequent in an extracranial dissection compared with an intracranial dissection. An extracranial location is independently associated with stenosis improvement in dissection patients.