The Blood-Cerebrospinal Fluid Barrier Dysfunction in Brain Disorders and Stroke: Why, How, What For?

Ischemic stroke (IS) results in the interruption of blood flow to the brain, which can cause significant damage. The pathophysiological mechanisms of IS include ionic imbalances, oxidative stress, neuroinflammation, and impairment of brain barriers. Brain barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (B-CSF), protect the brain from harmful substances by regulating the neurochemical environment. Although the BBB is widely recognized for its crucial role in protecting the brain and its involvement in conditions such as stroke, the B-CSF requires further study. The B-CSF plays a fundamental role in regulating the CSF environment and maintaining the homeostasis of the central nervous system (CNS). However, the impact of B-CSF impairment during pathological events such as IS is not yet fully understood. In conditions like IS and other neurological disorders, the B-CSF can become compromised, allowing the entry of inflammatory substances and increasing neuronal damage. Understanding and preserving the integrity of the B-CSF are crucial for mitigating damage and facilitating recovery after ischemic stroke, highlighting its fundamental role in regulating the CNS during adverse neurological conditions.

A neural cell automated analysis system based on pathological specimens in a gerbil brain ischemia model.

PURPOSE: Amid rising health awareness, natural products which has milder effects than medical drugs are becoming popular. However, only few systems can quantitatively assess their impact on living organisms. Therefore, we developed a deep-learning system to automate the counting of cells in a gerbil model, aiming to assess a natural product's effectiveness against ischemia. METHODS: The image acquired from paraffin blocks containing gerbil brains was analyzed by a deep-learning model (fine-tuned Detectron2). RESULTS: The counting system achieved a 79%-positive predictive value and 85%-sensitivity when visual judgment by an expert was used as ground truth. CONCLUSIONS: Our system evaluated hydrogen water's potential against ischemia and found it potentially useful, which is consistent with expert assessment. Due to natural product's milder effects, large data sets are needed for evaluation, making manual measurement labor-intensive. Hence, our system offers a promising new approach for evaluating natural products.

Sepsis after middle cerebral artery occlusion exacerbates peripheral oxidative stress in a sex-specific manner.

Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include post-stroke infection, as sepsis. Additionally, oxidative stress is recognized for inducing functional deficits in peripheral organs during sepsis. Therefore, sex differences in stroke exist and we aimed to investigate the peripheral oxidative stress caused by sepsis after stroke in male and female rats. Wistar rats (male and female) were divided into sham+sham, middle cerebral artery occlusion (MCAO) + sham, sham+ cecal ligation and perforation (CLP) and MCAO+CLP groups to males and female rats. Animals were subjected to MCAO or sham and after 7 days, were subjected to sepsis by CLP or sham. After 24 h, serum, total brain, lung, liver, heart, and spleen were collected. Brain edema, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, oxidative damage to lipids and proteins, and catalase activity were evaluated. Brain edema was observed only in male rats in MCAO+CLP group compared to MCAO+sham. Regarding MPO activity, an increase was verified in male in different organs and serum in MCAO+CLP group. For N/N levels, the increase was more pronounced in females submitted to MCAO+CLP. In general, to oxidative stress, an increase was only observed in animals exposed to MCAO+CLP, or with a greater increase in this group compared to the others. The findings provided the first indication that animals exposed to MCAO exhibit a heightened vulnerability to the harmful impacts of sepsis, as evidenced by brain edema and peripheral oxidative stress, and this susceptibility is dependent of sex.

Reproducibility of arterial spin labeling cerebral blood flow image processing: A report of the ISMRM open science initiative for perfusion imaging (OSIPI) and the ASL MRI challenge.

PURPOSE: Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis. METHODS: Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches. RESULTS: Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results. CONCLUSIONS: Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.

Perfusion tomography in early follow-up of acute traumatic subdural hematoma: a case series.

Perfusion Computed Tomography (PCT) is an alternative tool to assess cerebral hemodynamics during trauma. As acute traumatic subdural hematomas (ASH) is a severe primary injury associated with poor outcomes, the aim of this study was to evaluate the cerebral hemodynamics in this context. Five adult patients with moderate and severe traumatic brain injury (TBI) and ASH were included. All individuals were indicated for surgical evacuation. Before and after surgery, PCT was performed and cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were evaluated. These parameters were associated with the outcome at 6 months post-trauma with the extended Glasgow Outcome Scale (GOSE). Mean age of population was 46 years (SD: 8.1). Mean post-resuscitation Glasgow coma scale (GCS) was 10 (SD: 3.4). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). Preoperative CBF and MTT were 23.9 ml/100 g/min (SD: 6.1) and 7.3 s (1.3) respectively. After surgery, CBF increase to 30.7 ml/100 g/min (SD: 5.1), and MTT decrease to 5.8s (SD:1.0), however, both changes don't achieve statistically significance (p = 0.06). Additionally, CBV increase after surgery, from 2.34 (SD: 0.67) to 2.63 ml/100 g (SD: 1.10), (p = 0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome at 6 months was 0.94 (p = 0.054). One patient died with the highest preoperative MTT (9.97 s) and CBV (4.51 ml/100 g). CBF seems to increase after surgery, especially when evaluated together with the MTT values. It is suggested that the improvement in postoperative brain hemodynamics correlates to favorable outcome.

Ultrasound biomicroscopy in the quantification of brain perfusion parameters of a rat stroke model: Analysis of contrast agent bolus kinetic dynamics.

BACKGROUND: Ischemic stroke represents a significant global health concern, necessitating thorough investigations and the utilization of stroke animal models to explore novel treatment modalities and diagnostic imaging techniques. NEW METHOD: Ultrasound biomicroscopy (BMU), operating at a center frequency of 21 MHz, along with ultrasound contrast agents (UCAs), was used to quantify microcirculation cerebral blood flow in a rat model of ischemic stroke. The microcirculation parameters were derived from time intensity curve (TIC) plots obtained based on UCA-bolus kinetics. RESULTS: Semiquantitative perfusion-related parameters were assessed. The TIC curves showed differences in amplitude when compared intra-animal between the left and right sides, and three situations were observed: normal perfusion, hypoperfusion, and nonperfusion. ROC analysis of delays between the left and right time intensity peak (TIP) for regions of interest (ROIs) in the control and stroke-hypoperfusion groups revealed an optimal cutpoint of 0.39 s to indicate when hypoperfusion is occurring in rats, with a sensitivity of 93.33 % and a specificity of 80 %. COMPARISON WITH EXISTING METHOD(S): Ultrasound perfusion imaging through the temporal bone window has been clinically applied to stroke patients using a UCA bolus for TIC analysis. TIC parameters were correlated with MRI- and CT-based measurements. CONCLUSIONS: This investigation quantified cerebral blood flow in a rat model of ischemic stroke by measuring microcirculation parameters. The study demonstrated the efficacy of this approach as a valuable tool for conducting preclinical studies.

The Active Role of Pericytes During Neuroinflammation in the Adult Brain.

Microvessels in the central nervous system (CNS) have one of the highest populations of pericytes, indicating their crucial role in maintaining homeostasis. Pericytes are heterogeneous cells located around brain microvessels; they present three different morphologies along the CNS vascular tree: ensheathing, mesh, and thin-strand pericytes. At the arteriole-capillary transition ensheathing pericytes are found, while mesh and thin-strand pericytes are located at capillary beds. Brain pericytes are essential for the establishment and maintenance of the blood-brain barrier, which restricts the passage of soluble and potentially toxic molecules from the circulatory system to the brain parenchyma. Pericytes play a key role in regulating local inflammation at the CNS. Pericytes can respond differentially, depending on the degree of inflammation, by secreting a set of neurotrophic factors to promote cell survival and regeneration, or by potentiating inflammation through the release of inflammatory mediators (e.g., cytokines and chemokines), and the overexpression of cell adhesion molecules. Under inflammatory conditions, pericytes may regulate immune cell trafficking to the CNS and play a role in perpetuating local inflammation. In this review, we describe pericyte responses during acute and chronic neuroinflammation.

Variations of the cerebral arterial circle: morphological and clinical analysis / Variaciones del círculo arterial cerebral: análisis morfológico y clínico

SUMMARY: The variations knowledge of the cerebral arterial circle (CAC) is relevant due to its influence on the development of ischemic encephalic disorders. Among these variations, when the external diameter of the posterior communicating artery exceeds the posterior cerebral artery caliber, we have a fetal conformation of this circle. The aim of this study was to describe the variations of the CAC in Chilean individuals and to know the type of arterial conformation. Thirty adult brains were used to measure lengths and caliber of the pre-communicating segments of the anterior (A1) and posterior (P1) cerebral arteries, and the anterior (ACoA) and posterior (PCoA) communicating arteries. The arterial conformation type was established, and the length and caliber of these vessels were compared according to the right or left side. It was observed that 76.6 % of the CACs presented aplasia and / or hypoplasia. Of its components, PCoA was hypoplasic in 53.3 %, appearing bilaterally in 40 % of the subjects. The comparison according to the side, indicated that the mean length of A1 and PCoA on the right side was slightly higher. In the case of caliber, the mean of A1, P1 and PCoA was higher on the left side. Regarding P1 and PcoA caliber, 33 % of the CACs presented unilateral fetal conformation. Regardless of the variability presented by the CAC, there is consensus that PCoA exhibits the greatest variability. The understanding of this variability requires an analysis of the embryonic aspects that can explain the fetal conformation of the CAC in the adult.

RESUMEN: El conocimiento de las variaciones del círculo arterial cerebral (CAC) resultan relevantes por su influencia en el desarrollo de trastornos isquémicos encefálicos. De estas variaciones, los cambios del calibre de la arteria comunicante posterior (ACoP) determinan una conformación fetal de este círculo. El objetivo de este estudio fue describir las variaciones del CAC en individuos chilenos y conocer el tipo de conformación arterial. Se utilizaron 30 encéfalos adultos a los que se midieron las longitudes y calibres de los segmentos precomunicante de las arterias cerebrales anteriores (A1) y posteriores (P1), y de las arterias comunicante anterior (ACoA) y ACoP. Se estableció el tipo de conformación arterial y se comparó la longitud y calibre de estos vasos según lateralidad. Se observó que el 76,6 % de los CAC presentaron agenesias y/o hipoplasias. De sus componentes, la ACoP fue hipoplásica en el 53,3 %, presentándose bilateral en el 40 %. La comparación según lateralidad indicó que la longitud media de A1 y ACoP del lado derecho fueron levemente superiores. En el caso de los calibres, la media de A1, P1 y ACoP fue superior en el lado izquierdo. Respecto de los calibres de P1 y ACoP, el 33 % de los CAC presentaron conformación fetal unilateral. Independientemente de la variabilidad que presenta el CAC, existe consenso de que la ACoP exhibe la mayor variabilidad. La comprensión de esta variabilidad requiere un análisis de los aspectos embrionarios que pueden explicar la conformación fetal de esté círculo arterial en el adulto.

Arterial abnormalities and associated variations of the vertebrobasilar system on the brain base: apropos of a rare case / Anomalías arteriales y variaciones asociadas del sistema vertebrobasilar en la base del cerebro: un caso raro

SUMMARY: The presented case characterizes an association of primitive and definitive arteries with variations on the cadaveric brain base of a very old man. This case is found by the retrospective review of the data archive obtained during many years of cooperation of the author and co-authors. Fenestration of the (ectatic) basilar artery, partial and total duplication of some cerebellar arteries was associated with other variations of the vertebrobasilar and carotid systems. Although this is a case autopsied because of the myocardial infarction, the peculiarity of the case lies in the absence of the aneurysm based on the fenestration or dissection of one of the cerebral arteries.

RESUMEN: El caso presentado caracteriza una asociación de arterias primitivas y definitivas con variaciones sobre la base cerebral cadavérica de un anciano. Este caso se encuentra mediante la revisión retrospectiva de datos obtenidos durante muchos años de un trabajo de cooperación del autor y coautores. La fenestración de la arteria basilar (ectásica), la duplicación parcial y total de algunas arterias cerebelosas se asoció con otras variaciones de los sistemas vertebrobasilar y carotídeo. Si bien se trata de un caso de autopsia a causa de un infarto del miocardio, la peculiaridad del caso radica en la ausencia del aneurisma en base a la fenestración o disección de una de las arterias cerebrales.

Review of studies on dynamic cerebral autoregulation in the acute phase of stroke and the relationship with clinical outcome.

Acute stroke is associated with high morbidity and mortality. In the last decades, new therapies have been investigated with the aim of improving clinical outcomes in the acute phase post stroke onset. However, despite such advances, a large number of patients do not demonstrate improvement, furthermore, some unfortunately deteriorate. Thus, there is a need for additional treatments targeted to the individual patient. A potential therapeutic target is interventions to optimize cerebral perfusion guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). This narrative led to the development of the INFOMATAS (Identifying New targets FOr Management And Therapy in Acute Stroke) project, designed to foster interventions directed towards understanding and improving hemodynamic aspects of the cerebral circulation in acute cerebrovascular disease states. This comprehensive review aims to summarize relevant studies on assessing dCA in patients suffering acute ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage. The review will provide to the reader the most consistent findings, the inconsistent findings which still need to be explored further and discuss the main limitations of these studies. This will allow for the creation of a research agenda for the use of bedside dCA information for prognostication and targeted perfusion interventions.

Functional Recovery Caused by Human Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles Administered 24 h after Stroke in Rats.

Ischemic stroke is a major cause of death and disability, intensely demanding innovative and accessible therapeutic strategies. Approaches presenting a prolonged period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. Here, we evaluated the potential neuroprotective properties of nasally administered human adipose tissue mesenchymal stem cell (hAT-MSC)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. After a single intranasal EV (200 µg/kg) administered 24 h after a focal permanent ischemic stroke in rats, a higher number of EVs, improvement of the blood-brain barrier, and re-stabilization of vascularization were observed in the recoverable peri-infarct zone, as well as a significant decrease in infarct volume. In addition, EV treatment recovered long-term motor (front paws symmetry) and behavioral impairment (short- and long-term memory and anxiety-like behavior) induced by ischemic stroke. In line with these findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke.

Anatomical description and variations of the anterior arterial brain circulation in Colombian cadaveric specimens / Descripción anatómica y variaciones de la circulación cerebral arterial anterior en especímenes cadavéricos colombianos

SUMMARY: Understanding microsurgical neuroanatomy is a fundamental part of the training of neurosurgeons. Notwithstanding the fact that throughout history the study in cadavers has been a fundamental part of training, the publication of these studies has never marked a trend, and in our country the available studies are limited. A descriptive anatomical study was carried out on 22 specimens regarding the anatomical arrangement of the anterior circulation arteries of the brain and the most frequent anatomical variants in the sample used. To this end, bilateral pterional and bifrontal approaches were performed, obtaining a total of 132 arteries, including supraclinoid internal carotid arteries (ICA), anterior cerebral arteries in their A1 segment (ACA), and middle cerebral arteries in their M1 segment (MCA). measurements in each of these segments were made and anatomical variants were documented. Out of 22 cadaveric specimens, 17 (77 %) were male. the mean age was 59 years (range 36-81 years). Internal carotid artery mean length was 12.73 and 12.86 in the right and left side respectively. Anatomical variants identified were hypoplasia of segment A1 in 1 (4.5 %) specimen, duplication in 1 (4.5 %) and trifurcation of segment M1 in 3 (13.6 %) specimens. A similarity was found between our data and data reported by literature, with some differences, especially in the anterior communicating artery.

RESUMEN: Entender la neuroanatomía microquirúrgica es una parte fundamental de la formación de los neurocirujanos. A pesar de que, durante la historia, el estudio en cadáveres ha sido parte fundamental del entrenamiento, no ha sido tendencia la publicación de estos estudios, y en nuestro país son limitados los que se encuentran. Se realizó un estudio descriptivo anatómico en 22 especímenes acerca de la disposición anatómica de las arterias de la circulación cerebral anterior y las variantes anatómicas más frecuentes en población colombiana. Para dicho objetivo se realizaron abordajes bilaterales pterionales, y bifrontales obteniendo un total de 132 arterias incluyendo las arterias carotídeas internas supraclinoideas (ACI), arterias cerebrales anteriores en su segmento A1 (ACA) y las arterias cerebrales medias en su segmento M1 (ACM), se realizaron mediciones en cada uno de estos segmentos y se documentaron las variantes anatómicas. De los 22 especímenes cadavéricos, 17 (77 %) eran masculinos, la edad media fue de 59 años (rango 36-81 años). La longitud media de la arteria carótida interna fue de 12,73 mm en el lado derecho y de 12,86 mm en el lado izquierdo. Las variantes anatómicas identificadas fueron hipoplasia del segmento A1 en 1 (4,5 %), duplicación de A1 en 1 (4,5 %) y trifurcación del segmento M1 en 3 (13,6 %) muestras. Se encontró una similitud entre nuestros datos y los reportados por la literatura, con algunas diferencias, especialmente en el segmento de la arteria comunicante anterior.

Evaluación morfológica y variaciones del circulo arterial cerebral: un estudio con material cadavérico en una muestra de población colombianas / Morphological evaluation and variations of the cerebral arterial circle: a study with cadaveric material in a Colombian population sample

RESUMEN: El círculo arterial cerebral (CAC) mencionado también como polígono de Willis es una red de anastomosis vascular situado en la base del cerebro, constituido por ramas de la arteria carótida interna (ACI) y del sistema vertebro-basilar. Este estudio evaluó la morfología de las arterias que conforman el CAC en una muestra de individuos colombianos. Previa canalización de la ACI y de la arteria vertebral (AV), se perfundió con resina poliéster (palatal 85 % y estireno 15 %) los lechos vasculares del CAC de 70 encéfalos extraídos de cadáveres a quienes se les practicó necropsia en el Instituto de Medicina Legal de Bucaramanga, Colombia. La arteria comunicante anterior (ACoA) se observó en 68 encéfalos (97,1 %), con ausencia en 2 de las muestras (2,9 %); en promedio su diámetro fue de 1,91?1,04 mm y su longitud 2,21?0,97 mm respectivamente. Asimismo, se encontró hipoplasia en 6 muestras (8,4 %). La arteria comunicante posterior (ACoP) estuvo ausente en 2 de las muestras (5,7 %); su longitud fue 11,63?2,12 mm, mientras que su calibre fue de 1,21?0,58 mm, siendo ligeramente mayor en el lado derecho, sin diferencias estadísticamente significativas con relación al lado de presentación (p= 0,763). Se encontró hipoplasia de la ACoP en forma bilateral en 19 de las muestras (27,1 %) y unilateral en 15 muestras (21,4 %). En 8 muestras (20 %) de 35 CAC evaluados se observó configuración fetal. La incidencia de hipoplasia de la ACoP y de configuración fetal encontrados en el presente estudio, se ubican en el segmento superior de lo reportado en la literatura. Estas expresiones morfológicas han sido consideradas como coadyuvantes en el desarrollo de accidentes cerebro-vasculares (ACV).

SUMMARY: The cerebral arterial circle (CAC), also referred to as the polygon of Willis is a network of vascular anastomoses located at the base of the brain, consisting of branches of the internal carotid artery (ICA) and the vertebrobasilar system (VBS). This study evaluated the morphology of the arteries forming the CAC in a sample of Colombian individuals. After cannulation of the ICA and the vertebral artery (VA), the vascular beds of the ACC of 70 brains extracted from cadavers at the Institute of Legal Medicine of Bucaramanga, Colombia, were perfused with polyester resin (85 % palatal and 15 % styrene). The anterior communicating artery (ACoA) was observed in 68 brains (97.1 %), with absence in 2 of the samples (2.9 %); on average its diameter was 1.91?1.04mm and its length 2.21?0.97mm respectively. Likewise, hypoplasia was found in 6 samples (8.4 %). The posterior communicating artery (ACoP) was absent in 2 of the samples (5,7 %); its length was 11.63?2.12mm, while its caliber was 1.21?0.58mm, being slightly larger on the right side, with no statistically significant differences in relation to the side of presentation (p= 0.763). Hypoplasia of the ACoP was found bilaterally in 19 of the samples (27.1 %) and unilaterally in 15 samples (21.4 %). Fetal configuration was observed in 8 samples (20 %) of 35 CACs evaluated. The incidence of ACoP hypoplasia and fetal configuration found in the present study are in the upper segment of those reported in the literature. These morphological expressions have been considered as coadjuvants in the development of cerebrovascular accidents (CVA).

Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer's Disease Brains.

Alzheimer's disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid ß-peptide (Aß) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aß vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aß deposits on the NVU and the blood-brain barrier (BBB) are unknown. In this study, we analyze different Aß species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aß and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aß species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aß in AD.

The Neurovascular Unit Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid ß peptide (Aß) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aß clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aß. An increase in Aß amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aß or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.

Evaluating Cerebral Perfusion in Alzheimer Patients and First-Degree Relatives: Lessons from Artemisa Province, Cuba.

INTRODUCTION: Alzheimer disease is related to several risk factors including aging, family history, high blood pressure and diabetes. Studies have shown specific regional cerebral perfusion changes in patients with Alzheimer disease. Some authors state that these changes could appear years before patient memory becomes impaired, enabling early diagnosis in high-risk persons who appear to be healthy. OBJECTIVE: Determine the usefulness of cerebral perfusion studies in Alzheimer patients and first-degree relatives for obtaining additional diagnostic information and detecting functional changes that may suggest elevated disease risk. METHODS: This study involved 128 persons (87 clinically diagnosed with Alzheimer disease and 41 of their first-degree relatives with normal cognition), all from Artemisa Province, Cuba. We performed clinical, laboratory, neuropsychological and genetic (apolipoprotein E-ApoE, e4 allele) tests, as well as cerebral perfusion studies using single photon emission computed tomography after administering 740-925 MBq of 99m Tc-ECD, following internationally standardized protocols. RESULTS: In the Alzheimer disease group, the cerebral single photon emission computed tomography showed a typical Alzheimer pattern (bilateral posterior temporal-parietal hypoperfusion) in 77% (67/87) of participants; 35.9% (28/67) in stage 1; 51.3% (40/67) in stage 2; and 12.8% (10/67) in stage 3 of the disease. In this group, 12.7% (11/87) had mild or unilateral cerebral perfusion changes; 5.7% (5/87) vascular dementia; 3.4% (3/87) frontal dementia; and 1.2% (1/87) normal cerebral perfusion. Of the patients, 28.7% (25/87) received a different classification of stage and disease diagnosis after cerebral perfusion results were considered. In the relative group, 14.6% (6/41) had cerebral perfusion abnormalities. Among these, 7.1% (3/41) were mild bilateral temporal-parietal hypoperfusion; 4.8% (2/41) mild unilateral temporal-parietal hypoperfusion; and 2.4% (1/41) had perfusion defecits in their right frontal lobes. Of patients with typical Alzheimer disease patterns in the cerebral single photon emission computed tomography, 76.6% (52/67) had positive ApoE e4. All relatives with perfusion abnormalities (6/6) had positive ApoE e4. CONCLUSIONS: Cerebral perfusion studies confirmed the Alzheimer disease diagnosis, classified disease stages, and differentiated between the types of dementia. The test showed perfusion changes in several asymptomatic first-degree relatives with positive ApoE e4, which could be predictors of disease. The technique was useful for evaluating patients and their relatives.

Brain folding shapes the branching pattern of the middle cerebral artery.

The folds of the brain offer a particular challenge for the subarachnoid vascular grid. The primitive blood vessels that occupy this space, when the brain is flat, have to adapt to an everchanging geometry while constructing an efficient network. Surprisingly, the result is a non-redundant arterial system easily challenged by acute occlusions. Here, we generalize the optimal network building principles of a flat surface growing into a folded configuration and generate an ideal middle cerebral artery (MCA) configuration that can be directly compared with the normal brain anatomy. We then describe how the Sylvian fissure (the fold in which the MCA is buried) is formed during development and use our findings to account for the differences between the ideal and the actual shaping pattern of the MCA. Our results reveal that folding dynamics condition the development of arterial anastomosis yielding a network without loops and poor response to acute occlusions.

Red wine consumption mitigates the cognitive impairments in low-density lipoprotein receptor knockout (LDLr-/-) mice.

Although the benefits of moderate intake of red wine in decreasing incidence of cardiovascular diseases associated to hypercholesterolemia are well recognized, there are still widespread misconceptions about its effects on the hypercholesterolemia-related cognitive impairments. Herein we investigated the putative benefits of regular red wine consumption on cognitive performance of low-density lipoprotein receptor knockout (LDLr-/-) mice, an animal model of familial hypercholesterolemia, which display cognitive impairments since early ages. The red wine was diluted into the drinking water to a final concentration of 6% ethanol and was available for 60 days for LDLr-/- mice fed a normal or high-cholesterol diet. The results indicated that moderate red wine consumption did not alter locomotor parameters and liver toxicity. Across multiple cognitive tasks evaluating spatial learning/reference memory and recognition/identification memory, hypercholesterolemic mice drinking red wine performed significantly better than water group, regardless of diet. Additionally, immunofluorescence assays indicated a reduction of astrocyte activation and lectin stain in the hippocampus of LDLr-/- mice under consumption of red wine. These findings demonstrate that the moderate consumption of red wine attenuates short- and long-term memory decline associated with hypercholesterolemia in mice and suggest that it could be through a neurovascular action.

Anatomy of the dura mater venous sinus of Alouatta belzebul.

The anatomy of the dura mater's venous sinuses is important in the veterinary clinical and surgical area, for cranial procedures and interventions of wild animals, in addition to assisting in the management of neurological diseases, which can prevent serious complications. The macroscopic anatomy of the venous sinuses of the dura mater of Alouatta belzebul was studied. Five adult specimens, males and females, were dissected and fixed in 10% formaldehyde solution. In the dura mater of the Alouatta belzebul, nine venous sinuses were observed, being them dorsal sagittal sinus, ventral sagittal sinus, transverse sinus, straight sinus, sigmoid sinus, temporal sinus, parietal sinus, basilar sinus and cavernous sinus, with morphological similarities in origin, path and destination of blood flow to the internal jugular vein, assisting in the venous drainage function of the brain in this species. These data are similar to those found in other species of non-human and human primates such as Saimiri sciureus, Sapajus libidinosus and Homo sapiens. Of the venous sinuses observed, the cavernous sinus was of considerable clinical and surgical importance in Alouatta belzebul due to its topographic arrangement next to the internal carotid artery and pituitary gland, data that corroborate Sapajus libidinosus, Macaca fascicularis, Macaca mulatta, Papio ursinus, Cercopithecus pygerithrus and Galago senegalensis. In this context, the knowledge of the macroscopic anatomy of the venous sinuses of the dura mater may contribute to the role of veterinarians in less invasive surgical procedures in non-human primates such as Alouatta belzebul and other mammals.

Anatomic study of the arterial vascularization of the brain base of paca (Cuniculus paca) / Estudo anatômico da vascularização arterial da base do encéfalo da paca (Cuniculus paca)

Paca (Cuniculus paca Linnaeus, 1766), rodent belong to the Cuniculidae family, has encouraged numerous scientific researches and for this reason could be an experimental model in both human and veterinary areas. And recently, the economic exploitation of the meat cuts, has being direct implication in its zootechnical importance. However, no anatomical descriptions regarding the vascularization of the base of the brain in this rodent has being found. Thus, the aim of the present study was to describe the arteries and the pattern of the vasculature and to compare it with the other species already established in the literature. For this, five pacas, donated by the Unesp Jaboticabal Wildlife Sector, were euthanized followed by the vascular arterial system was injected with red-stained-centrifuged latex by the common carotid artery. After craniectomy, the brains were removed and the arteries were identified and, in addition, compared with those described in other animal species. The presence of the right and left vertebral arteries, close to the medulla oblongata, was detected, originating the basilar artery, which divided into the terminal branches of the right and left basilar artery. Ventral to the optic tract there was the right internal carotid artery and the left, dividing the middle cerebral artery and left rostral and right; dorsal to the optic chiasm, the medial branch of the rostral cerebral arteries was identified. Based on the results, it is concluded that the vascularization of the paca brain base is supplied by the carotid and vertebrobasilar system.(AU)

A paca (Cuniculus paca Linnaeus 1766), roedor da família Cuniculidae, tem encorajado inúmeras pesquisas científicas, tornando-a modelo experimental tanto na área humana quanto na veterinária, além da recente exploração econômica de seus cortes cárneos, que favoreceu diretamente sua importância zootécnica. No entanto, não há até o momento, descrições anatômicas referentes à padronização da vascularização da base do encéfalo neste roedor. Assim, o objetivo do presente trabalho foi realizar tal delineamento arterial nessa região do sistema nervoso central e compará-lo com as demais espécies já estabelecidas na literatura. Para isso, foram eutanasiadas cinco pacas doadas pelo setor de Animais Silvestres da Unesp Jaboticabal, as quais foram submetidas posteriormente à injeção de látex centrifugado e corante líquido xadrez vermelho, pela artéria carótida comum. Após craniectomia e segregação do encéfalo de todos os cadáveres, realizou-se a identificação das artérias presentes na base deste órgão e, ademais, comparação destas com as descritas cientificamente em outras espécies animais. Detectou-se a presença das artérias vertebral direita e esquerda, próximas à medula oblonga, originando a artéria basilar, que se dividiu nos ramos terminais da artéria basilar direito e esquerdo. Ventral ao trato óptico verificou-se a artéria carótida interna direita e esquerda dividindo-se na artéria cerebral média e rostral direita e esquerda; ainda, dorsal ao quiasma óptico, identificou-se o ramo medial das artérias cerebrais rostrais. Com base nos resultados obtidos, conclui-se que a vascularização da base do encéfalo da paca é suprida pelo sistema carotídeo e vertebro-basilar.(AU)