Changes in the Proteome of the Circle of Willis during Aging Reveal Signatures of Vascular Disease.

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.

Establishment of a novel protocol for assessing the severity of subarachnoid hemorrhage in circle Willis perforation mouse model.

The Circle of Willis perforation (cWp) mouse model is a key tool in subarachnoid hemorrhage (SAH) research; however, inconsistent bleeding volumes can challenge experimental reliability. To address this issue, we introduced the ROB Scoring System, a novel protocol integrating Rotarod Tests (RT), Open-field Tests (OT) video analysis, and daily Body Weight Loss (BWL) monitoring to precisely categorize SAH severity. Forty C57BL/6 mice underwent cWp SAH induction, categorized by ROB into severity subgroups (severe, moderate, mild). Validation compared ROB trends in subgroups, and ROB outcomes with autopsy results on postoperative days three and seven for acute and sub-acute evaluations. Mortality rates were analyzed via the survival log-rank test, revealing a significant difference among SAH subgroups (P < 0.05). Strong correlations between ROB grades and autopsy findings underscored its precision. Notably, the severe group exhibited 100% mortality within 4 days post SAH onset. Single parameters (RT, OT, BWL) were insufficient for distinguishing SAH severity levels. The ROB score represents a significant advancement, offering an objective method for precise categorization and addressing inherent bleeding variations in the cWp SAH model. This standardized protocol enhances the reliability and effectiveness of the SAH translational research, providing a valuable tool for future investigations into this critical area.

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%.

Vasoespasmo cerebral y déficit isquémico tardío en la hemorragia subaracnoídea aneurismática: guías para su manejo clínico / Cerebral vasospasm and delayed ischemic deficit in the aneurysmal subarachnoid hemorrhage: guidelines to its clinical management

La presente revisión del tema Vasoespasmo y Déficit Isquémico Cerebral tardío (DIT) en la Hemorragia subaracnoidea aneurismática tiene como objetivo actualizar su manejo, basado en las hipótesis mas aceptadas que se han logrado para explicar su patogénesis. Se efectúa una introducción con conceptos generales, se revisan las bases patogénicas del Vasoespasmo y se plantea su manejo, tomando en cuenta su diagnóstico, monitorización, profilaxis y manejo avanzado de acuerdo a las últimas Guías de Manejo Clínico y según medicina basada en las evidencias.

The objective of the present review on cerebral vasospasm and cerebral delayed isquemic deficit due to subarachnoid haemorrhage secondary to ruptured cerebral aneurysm, is to update their management, based on the most accepted pathophysiological hypotesis explaining their pathogenetic mechanisms. An introduction is performed presenting general concepts, review of the most recent research works explaining their pathogenesis, and the management is stated touching diagnosis, monitoring, prophylaxis, and advanced management according with the last clinical guidelines for his management using medicine based on evidences.

Hemangioma facial como clave diagnóstica de PHACES / Facial haemangioma as a diagnostic key of PHACES

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Carotid siphon geometry and variants of the circle of Willis in the origin of carotid aneurysms / Geometria do sifão carotídeo e variantes do polígono de Willis na origem de aneurismas da carótida

This study evaluated anatomical variants in the carotid siphon and of the circle of Willis in patients with aneurysms. We performed a retrospective analysis of cerebral angiographies. The Control Group was composed of patients without aneurysms. Posterior communicating artery (PcomA) aneurysms were more common in women (p<0.05), and the anterior communicating artery (AcomA) aneurysms in men (p<0.1). The incidence of fetal-type PcomA was higher in cases with co-occurring PcomA aneurysm (24 versus 8%, p<0.05). Patients with AcomA aneurysm had higher incidence of A1 hypoplasia (p<0.0001, OR=32.13, 95%CI 12.95-79.71) and lower frequency of fetal-type PcomA compared to their control counterparts (p=0.0125). The angle of carotid siphon was narrower in patients with PcomA aneurysm (27.3±19.1 versus 34.8±22.6, p=0.028). In conclusion, a narrower carotid siphon or the presence of fetal-type PcomA or A1 hypoplasia may cause hemodynamic stress, thereby promoting the formation of aneurysms in susceptible individuals.

O presente estudo avaliou as variantes anatômicas do sifão carotídeo e da parte posterior do polígono de Willis em pacientes com aneurismas. Foi realizada uma análise retrospectiva de angiografias cerebrais. O Grupo Controle foi composto por pacientes sem aneurismas. Aneurismas da artéria comunicante posterior (ACP) foram mais frequentes em mulheres (p<0,05), e aqueles da anterior (ACA) em homens (p<0,1). A incidência do tipo fetal da ACP foi maior nos casos com co-ocorrência de aneurisma da ACP (24 versus 8%, p<0,05). Pacientes com aneurisma da ACA tiveram maior incidência de hipoplasia A1 (p<0,0001, OR=32,13, IC95% 12,95-79,71) e menor frequência do da ACP fetal comparados com os controles (p=0,0125). O ângulo do sifão carotídeo era mais estreito em pacientes com aneurismas da ACP (27,3±19,1 versus 34,8±22,6, p=0,028). Em conclusão, um sifão carotídeo estreito e a presença de ACP fetal ou hipoplasia A1 podem causar estresse hemodinâmico, promovendo a formação de aneurismas em indivíduos suscetíveis.

Variaciones morfológicas del círculo arterial en fallecidos con enfermedades cerebrovasculares Isquémicas / Morphological variations of the arterial circle in the deceased with ischemic cerebrovascular disease

Se realiza un estudio con el objetivo de describir variaciones morfológicas del encéfalo en fallecidos por enfermedades cerebrovasculares isquémicas (ECVI) en el Hospital General Docente Dr Agostinho Neto de Guantánamo, en el período enero-junio de 2010. El universo está constituido por el total de fallecidos en dicha entidad hasta 2010 y, la muestra, por 134 encéfalos de individuos que al morir presentaron diagnóstico de ECVI. La información primaria es tomada de controles estadísticos, historias clínicas, libro de necropsias del hospital y plasmada en una ficha de vaciamiento. Se seleccionan variables como: edad, sexo, configuración del polígono de Willis y variaciones arteriales. Predomina el sexo masculino y el grupo de edades de 80-89, color de piel mestizo, así como círculos arteriales con modificaciones no clásicos, que en la mayoría de los individuos está dada por el aspecto delgado de las arterias, afectando fundamentalmente a la ACoP derecha. Se recomienda relacionar los resultados obtenidos en encéfalos de fallecidos por enfermedades cerebrovasculares isquémicas con los de fallecidos por otras causas (AU)

A research is done at the Microbiology lab of the Provincial Center of Hygiene Epidemiology and Microbiology (CPHEM) from January to March 2009 with the aim to determine antimicrobial resistance in 73 strains of microorganisms isolated and identified from sputum samples of patients with lower respiratory infections. Determine the sensitivity and resistance to antimicrobials in vitro by the Kirby Bauer method. The results are expressed in two-dimensional table and the summary measure was used by percentage. The highest number of bacteria was identified gram-negative bacilli. The greatest resistance is shown by the Pseudomonas aeruginosa, Staphylococcus aureus, followed by Klebsiella pneumoniae. As a conclusion antimicrobial resistance is an emerging problem, which requires the proper selection and identification of the etiologic agent

Tratamiento quirúrgico de los aneurismas intracraneales gigantes de la circulación anterior del circulo de Willis / Surgical treatment of giant intracranial aneurysms of the anterior circulation of the circle of Willis

Introducción: Los aneurismas intracraneales gigantes, son lesiones con características muy particulares, que implican la utilización de métodos quirúrgicos específicos para su exclusión de la circulación, dependientes de su tamaño, localización, morfología, relaciones con otras estructuras neurales y vasculares, así como características propias del saco. Método: Se realiza un estudio descriptivo, de todos los pacientes portadores de aneurismas intracraneales gigantes, que fueron intervenidos quirúrgicamente en el servicio de neurocirugía del Hospital “Roberto Rodriguez”, de la ciudad de Morón, en la provincia de Ciego de Ávila, Cuba, en el período comprendido entre enero de 1996 y diciembre del 2008. La evaluación al ingreso fue con la escala de Hunt y Hess, el diagnóstico se obtuvo con imágenes de angiotomografía computarizada multicortes, angioresonancia magnética nuclear o angiografía cerebral. El corredor quirúrgico fue el frontopterional de Yasargil y se emplearon medidas adyuvantes para lograr el presillamiento. Resultados: La muestra estuvo representada por 13 pacientes. Predominaron los aneurismas de la comunicante posterior (61,53 por ciento), ocho (61,54 por ciento), debutaron con una hemorragia subaracnoidea y cinco (38,46 por ciento), con compresión de estructuras adyacentes. De los tres operados en fase aguda, dos fallecieron (ERG I) (66,67 por ciento) y uno (33,33 por ciento) quedó con secuelas severas (ERG III). Los operados en fase tardía, dos (20 por ciento) quedaron con secuelas severas (ERG III), tres (30 por ciento) mostraron secuelas moderadas (ERG IV) y cinco (50 por ciento) quedaron con secuelas ligeras o sin ellas (ERG V). La mortalidad global fue de 15,38 por ciento. Conclusiones: La microcirugía constituye un método eficaz en centros que no cuentan con tratamiento endovascular.

Introduction: The surgical treatment of giant intracraneal aneurysms aims to exclude them from the circulation and to reduce its mass effect while preserving normal vasculature. Method: We have carried out a descriptive study in thirteen patients with a giant aneurysm located in the anterior circulation of Willis circle operated on in neurological surgery department of Moron General Hospital, Ciego de Avila, Cuba between January of 1996 to December of 2008. The neurological status in emergency department was evaluated by Hunt and Hess scale, the results were evaluated by Glasgow outcome scale. The diagnosis was obtained by CT scan, MRI and conventional angiography. Results: From thirteen aneurysms, 9 were excluded of circulation (69,23 percent), 7 were clipped, 2 were trapped and 4 reinforced. Three patients were operated on in acute phase with poor grade aneurysmal subarachnoid hemorrhage, two of them died (66,67 percent) (GOS I), and one (33,33 percent) had a severe disability (GOS III). Delayed surgery was carried out in 10 patients, two of them (20 percent) showed severe disability (GOS III), 3 (30 percent) had moderate disability and 5 (50 percent) had favorable outcome (GOS 5). The global mortality in the group was 15,38 percent. Conclusion: Microsurgery is the more important treatment in countries without possibilities of endovascular treatment for giant intracranial aneurysms.

Características morfológicas de aneurimas cerebrales del polígono de Willis: estudioanatómico directo / Morphological characteristics of cerebral aneurysm of Willis’ circle: a direct anatomical study

Objetivo. Determinar la prevalencia y las característicasmorfológicas de los aneurismas sin ruptura del círculoarterial del cerebro en una muestra de poblaciónmestiza colombiana.Materiales y métodos. Mediante abordaje y canalizaciónde las arterias carótidas comunes y vertebrales serealizó inyección de resina mezclada con rojo minerala 125 encéfalos de individuos masculinos, entre 16 y 65años, raza mestiza, a quienes se les practicó autopsia enel Instituto de Medicina Legal, Bucaramanga - Colombia.Se realizó exéresis y fijación de los encéfalos, posteriormentebajo lupa de aumento se identificaron lossegmentos del círculo arterial del cerebro y las lesionesaneurismáticas ubicadas a este nivel.Resultados. Se observaron nueve aneurismas enseis cerebros (4.8%); la localización mas frecuentefue el segmento supraclinoideo de la arteria carótidainterna, con 4 casos (44.4%) de los cuales 3 se ubicaronen el origen de la arteria coroidea anterior. En la arteriacomunicante anterior se localizaron 3 aneurismas(33.3%); los casos restantes se ubicaron, uno (11.1%)en el segmento precomunicante de la arteria cerebralanterior y otro en la bifurcación de la arteria basilar.La media del tamaño de las lesiones aneurismáticasfue de 2.49 mm DS 0.37. Los encéfalos con aneurismaspresentaron concomitantemente alguna variación enla configuración del círculo arterial del cerebro, conpredominio de la hipoplasia de la arteria comunicanteposterior.Conclusiones. La prevalencia de aneurismas en lamuestra evaluada es similar a lo informado en otrosgrupos poblacionales. Se destaca la presencia de aneurismasen el origen de la arteria coroidea anterior, localizaciónseñalada en la literatura como poco frecuente (AU)

Objective. To determine the prevalence and morphologiccharacteristics of unruptured aneurysms of Willis’circle in a sample of mestizo Colombian population.Materials and methods. A mixture of resin and mineralred was injected into cerebral arteries by dissectionand canalization of common carotids and vertebralarteries of the encephalons of 125 mestizo male cadaversof 16 to 65 years old. The procedure was carriedout during the autopsy course at the Legal MedicineInstitute, Bucaramanga - Colombia. Then the encephalonswere extracted and fixed. After that, the Willis’circles were identified and the presence of aneurysms atthis level was determined with magnifying glass.Results. A total of nine aneurysms were observedin six brains (4.8%). The most frequent location wasthe supraclinoid segment of the intern carotid artery,with 4 cases (44.4%), three of which were localized inthe origin of the anterior choroidal artery. Additionally,three aneurysms were found in the anterior communicatingartery (33.3%). From the remaining cases, one(11.1%) was localized in the pre-communicating segmentof the anterior cerebral artery, and the other inthe bifurcation of the basilar artery. The average size ofthe aneurysms was 2.49 mm SD 0.37. The affected encephalonspresented concomitant variations of the Willis’circle configuration, being predominant the presence ofhypoplasic posterior communicanting arteries.Conclusion. The aneurysm prevalence in the evaluatedsample was similar to the reported in otherpopulations. In this work, the presence of aneurysms onthe origin of the anterior chorioid artery, an unusually reported localization, was prominent (AU)