RESUMEN

Cerebral aneurysms (CA) are a type of vascular disease that causes significant morbidity and mortality with rupture. Dysfunction of the vascular smooth muscle cells (VSMCs) from circle of Willis (CoW) vessels mediates CA formation, as they are the major cell type of the arterial wall and play a role in maintaining vessel integrity. Dimethyl fumarate (DMF), a first-line oral treatment for relapsing-remitting multiple sclerosis, has been shown to inhibit VSMC proliferation and reduce CA formation in a mouse model. Potential unwanted side effects of DMF on VSMC function have not been investigated yet. The present study characterizes the impact of DMF on VSMC using single-cell RNA-sequencing (scRNA-seq) in CoW vessels following CA induction and further explores its role in mitochondrial function using in vitro VSMC cultures. Two weeks of DMF treatment following CA induction impaired the transcription of the glutathione redox system and downregulated mitochondrial respiration genes in VSMCs. In vitro, DMF treatment increased lactate formation and enhanced the mitochondrial production of reactive oxygen species (ROS). These effects rendered VSMCs vulnerable to oxidative stress and led to mitochondrial dysfunction and enhancement of apoptosis. Taken together, our data support the concept that the DMF-mediated antiproliferative effect on VSMCs is linked to disturbed antioxidative functions resulting in altered mitochondrial metabolism. This negative impact of DMF treatment on VSMCs may be linked to preexisting alterations of cerebrovascular function due to renal hypertension. Therefore, before severe adverse effects emerge, it would be clinically relevant to develop indices or biomarkers linked to this disturbed antioxidative function to monitor patients undergoing DMF treatment.

RESUMEN

BACKGROUND: The circle of Willis (CoW) is the most common location for aneurysms to form in humans. Although the major cell types of the intracranial vasculature are well known, the heterogeneity and relative contributions of the different cells in healthy and aneurysmal vessels have not been well characterized. Here, we present the first comprehensive analysis of the lineage heterogeneity and altered transcriptomic profiles of vascular cells from healthy and aneurysmal mouse CoW using single-cell RNA sequencing. METHODS: Cerebral aneurysms (CAs) were induced in adult male mice using an elastase model. Single-cell RNA sequencing was then performed on CoW samples obtained from animals that either had aneurysms form or rupture 14 days post-induction. Sham-operated animals served as controls. RESULTS: Unbiased clustering analysis of the transcriptional profiles from >3900 CoW cells identified 19 clusters representing ten cell lineages: vascular smooth muscle cells, endothelial cells fibroblasts, pericytes and immune cells (macrophages, T and B lymphocytes, dendritic cells, mast cells, and neutrophils). The 5 vascular smooth muscle cell subpopulations had distinct transcriptional profiles and were classified as proliferative, stress-induced senescent, quiescent, inflammatory-like, or hyperproliferative. The transcriptional signature of the metabolic pathways of ATP generation was found to be downregulated in 2 major vascular smooth muscle cell clusters when CA was induced. Aneurysm induction led to significant expansion of the total macrophage population, and this expansion was further increased with rupture. Both inflammatory and resolution-phase macrophages were identified, and a massive spike of neutrophils was seen with CA rupture. Additionally, the neutrophil-to-lymphocyte ratio (NLR), which originated from CA induction mirrored what happens in humans. CONCLUSIONS: Our data identify CA disease-relevant transcriptional signatures of vascular cells in the CoW and is searchable via a web-based R/shiny interface.

Asunto(s)

Aneurisma Intracraneal , Adulto , Animales , Círculo Arterial Cerebral , Modelos Animales de Enfermedad , Células Endoteliales , Perfilación de la Expresión Génica , Humanos , Aneurisma Intracraneal/inducido químicamente , Aneurisma Intracraneal/genética , Masculino , Ratones , Rotura , Transcriptoma

RESUMEN

The eponymous term torcular Herophili has been used for the confluence of sinuses. Although no original writings of Herophilus are extant, his accomplishments and descriptions live on in the writings of such authors as Galen. However, in regard to the torcular Herophili, there are some inconsistencies in the secondary sources and their translations regarding what was actually originally described by Herophilus. Herein, we review the history of the term torcular Herophili, which is so often used in clinical medicine.

Asunto(s)

Senos Craneales , Humanos

RESUMEN

BACKGROUND: The blood supply to the skull base is important to surgeons and those performing interventional and diagnostic procedures in this region. However, 1 vessel with a vast distribution in this area, the dorsal meningeal artery (DMA), has had few anatomic studies performed to investigate not only its normal anatomy but also its variations. Therefore the current study aimed to analyze the DMA via cadaveric dissection. METHODS: In 10 adults, latex-injected, cadaveric heads (20 sides), the DMA was dissected using a surgical microscope. This artery and its branches were documented and measured. RESULTS: A DMA was identified on all sides. In the majority (85%), it was a branch of the meningohypophysial trunk or common stem with either the inferior hypophysial or tentorial arteries and always had branches that traversed the basilar venous plexus. Multiple branches of the DMA were identified and categorized as bony, dural, neural, and vascular. CONCLUSIONS: Surgeons operating at the skull base or clinicians interpreting imaging of this area should have a good working knowledge of the DMA and its typical and variant anatomy.

Asunto(s)

Arterias Meníngeas/diagnóstico por imagen , Arterias Meníngeas/cirugía , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Arterias Meníngeas/anatomía & histología , Procedimientos Neuroquirúrgicos , Base del Cráneo/anatomía & histología , Base del Cráneo/irrigación sanguínea

RESUMEN

OBJECTIVE: Diet-related diseases are the leading cause of morbidity and mortality in the USA. While the critical aspects of a healthy diet are well known, the relationship between community-based, teaching kitchen education and dietary behaviours is unclear. We examined the effect of a novel culinary medicine education programme on Mediterranean diet adherence and food cost savings. DESIGN: Families were randomised to a hands-on, teaching kitchen culinary education class (n = 18) or non-kitchen-based dietary counselling (n = 23) for 6 weeks. The primary outcome was adherence to the validated nine-point Mediterranean diet score, and the secondary outcome was food cost savings per family. SETTING: The Goldring Center for Culinary Medicine, a community teaching kitchen in New Orleans. PARTICIPANTS: Families (n = 41) of at least one child and one parent. RESULTS: Compared with families receiving traditional dietary counselling, those participating in hands-on, kitchen-based nutrition education were nearly three times as likely to follow a Mediterranean dietary pattern (OR 2·93, 95% CI 1·73, 4·95; P  <  0·001), experiencing a 0·43-point increase in Mediterranean diet adherence after 6 weeks (B  =  0·43; P  <  0·001). Kitchen-based nutrition education projects to save families $US 21·70 per week compared with standard dietary counselling by increasing the likelihood of consuming home-prepared v. commercially-prepared meals (OR 1·56, 95% CI 1·08, 2·25; P  =  0·018). CONCLUSIONS: Community-based culinary medicine education improves Mediterranean diet adherence and associates with food cost savings among a diverse sample of families. Hands-on culinary medicine education may be a novel evidence-based tool to teach healthful dietary habits and prevent chronic disease.

Asunto(s)

Dieta Mediterránea , Niño , Ahorro de Costo , Curriculum , Alimentos , Educación en Salud , Humanos

RESUMEN

Background. Adherence to Mediterranean dietary patterns reduces the incidence of cardiovascular disease and other major chronic diseases. We aimed to assess the association between participation in kitchen-based nutrition education and Mediterranean diet intake and lifestyle medicine counseling competencies among medical trainees. Methods. The Cooking for Health Optimization with Patients (CHOP) curriculum is a hands-on cooking-based nutrition education program implemented at 32 medical programs (4125 medical trainees) across the United States. Mediterranean diet intake, nutrition attitudes, and lifestyle medicine counseling competencies were assessed via validated surveys. Multivariable-adjusted logistic regression assessed the relationship of CHOP education with Mediterranean diet intake, nutrition attitudes, and lifestyle medicine counseling competencies. Results. Individuals participating in the CHOP program were 82% more likely to follow the Mediterranean diet compared with those receiving traditional nutrition education (OR = 1.82; P < .001). CHOP participants were more likely to satisfy daily intake of fruits (OR = 1.33; P = .019) and vegetables (OR = 2.06; P < .001) and agree that nutrition counseling should be a routine component of clinical care (OR = 2.43; P < .001). Kitchen-based nutrition education versus traditional curricula is associated with a higher likelihood of total counseling competency involving 25 lifestyle medicine categories (OR = 1.67; P < .001). Conclusion. Kitchen-based nutrition education is associated with cardioprotective dietary patterns and lifestyle medicine counseling among medical trainees.