Effects of physical exercise on cognition and glymphatic system of patients with mild cognitive impairment or Alzheimer's disease ­ study protocol

Objective: To evaluate the impact of a multicomponent physical exercise program on clinical variables associated with the glymphatic clearance system, sleep-awake patterns, and cognitive function in individuals with mild cognitive impairment or mild Alzheimer's disease. Methods: This is a single-center parallel randomized controlled trial involving pre- and post-intervention assessments. The intervention consists of a 12 (±3)-week multicomponent aerobic and resistance physical exercise program of moderate intensity divided into 2 groups: an experimental group (undergoing multicomponent training) and a control group (no intervention). Eligible participants are those diagnosed with probable mild cognitive impairment or mild Alzheimer's disease. Expected results: Anticipated outcomes suggest that the multicomponent training protocol, incorporating both aerobic and resistance physical exercises at a moderate intensity, will yield improvements in glymphatic clearance dynamics, sleep-awake parameters, and performance on cognitive, functional, and behavioral tasks among eligible patients. Relevance: The need to move beyond cognitive clinical testing justifies our trial, which proposes an assessment employing neuroimaging techniques and the analysis of biomarkers present in cerebrospinal fluid in conjunction with clinical tests for physical and cognitive assessment. (AU)

Sistema glinfático: aspectos anatómicos, fisiológicos e implicaciones clínicas / Glymphatic system: Anatomo-physiological principles and their clinical implications

Introducción: El sistema glinfático comprende el conjunto de rutas perivasculares tanto arteriales como venosas que se encuentran en estrecha asociación con células astrogliales y que permiten la interacción entre el líquido cefalorraquídeo (LCR) y el líquido intersticial cerebral (LIC), para llevar a cabo procesos como la depuración de los metabolitos de desecho celular, o la distribución de nutrientes, así como contribuir al metabolismo cerebral local, la transmisión de volumen y la señalización paracrina cerebral. Contenidos: Este artículo busca profundizar en los conceptos anatómicos y fisiológicos, hasta el momento descritos, sobre este sistema macroscópico de transporte. Se realiza una búsqueda bibliográfica de revisiones y estudios experimentales sobre la anatomía, la fisiología y las implicaciones fisiopatológicas del sistema glinfático. Conclusiones: La identificación anatómica y funcional del sistema glinfático ha ampliado el conocimiento sobre la regulación del metabolismo cerebral en cuanto a distribución de nutrientes y cascadas de señalización celular. Al establecer una interacción entre el espacio subaracnoideo subyacente y el espacio intersticial cerebral, el sistema glinfático surge como uno de los mecanismos protagonistas de la homeostasis cerebral. La disfunción de esta vía hace parte de los mecanismos fisiopatológicos de múltiples trastornos neurológicos, ya sea por la acumulación de macromoléculas, como ocurre en la enfermedad de Alzheimer, o por la reducción del drenaje de sustancias químicas y citocinas proinflamatorias en patologías como la migraña o el trauma craneoencefálico.

Introduction: The glympathic system comprises the set of perivascular routes, arterials or venous, that are found in close relationship with astroglial cells and allow interaction between the cerebrospinal fluid (CSF) and the interstitial brain fluid (ISF), to carry processes like cell-wasting metabolites depuration, nutrients distribution, as well as make a contribution in the local brain metabolism, volumen transmition and brain paracrine signaling. Contents: This article seeks to deepen in the anatomical and physiological concepts, so far described, about this macroscopic transport system. A bibliographic search of reviews and experimental studies on the anatomy, physiology and pathophysiological implications of the glymphatic system is carried out. Conclusions: Anatomical and functional identification of glympathic system has broaden the knowledge about regulation of brain metabolism on the nutrients distribution and cell signaling cascades. When setting an interaction between the subarachnoid space and the brain interstitial space, the glymphatic system arise as one of the leading mechanisms of brain homeostasis. Disfunction of this pathway makes part of the patophysiological mechanisms of multiple neurological disease, either be by collection of macromolecules as in Alzheimer's disease, or by the reduction of inflammatory cytokines and chemical substances drainage as in migraine or traumatic brain injury (TBI).

Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders / 神经科学通报·英文版

The concept of the glial-vascular unit (GVU) was raised recently to emphasize the close associations between brain cells and cerebral vessels, and their coordinated reactions to diverse neurological insults from a "glio-centric" view. GVU is a multicellular structure composed of glial cells, perivascular cells, and perivascular space. Each component is closely linked, collectively forming the GVU. The central roles of glial and perivascular cells and their multi-level interconnections in the GVU under normal conditions and in central nervous system (CNS) disorders have not been elucidated in detail. Here, we comprehensively review the intensive interactions between glial cells and perivascular cells in the niche of perivascular space, which take part in the modulation of cerebral blood flow and angiogenesis, formation of the blood-brain barrier, and clearance of neurotoxic wastes. Next, we discuss dysfunctions of the GVU in various neurological diseases, including ischemic stroke, spinal cord injury, Alzheimer's disease, and major depression disorder. In addition, we highlight the possible therapies targeting the GVU, which may have potential clinical applications.

Research progress in the evaluation of glymphatic system function by the DTI-ALPS method / 中南大学学报(医学版)

The glymphatic system can remove metabolic wastes from the brain, which plays a significant role in maintaining the homeostasis of the central nervous system. It is an important basis for advanced cognitive functions such as learning and memory. Studies have analyzed the function of glymphatic system by diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) recently. Compared with other invasive examinations that require fluorescent tracer technique or the injection of contrast agents, DTI-ALPS can evaluate the hydromechanics of the glymphatic system via quantifying the diffusion rate of water molecules in different directions, which turns out to be a non-invasive in vivo neuroimaging method. The ALPS-index calculated by the DTI-ALPS method is significantly correlated with the cognitive function in diseases of central nervous system and other system and can reflect the dynamic changes of diseases. In general, ALPS-index is expected to become a novel neuroimaging biomarker for predicting prognosis and clinical effects.

Avances recientes en el diagnóstico imagenológico de la hidrocefalia en niños. Revisión de la literatura de los últimos seis años / Recent advances of the imagological diagnosis of hydrocephalus in children. Review of the literature of the last six years

Resumen La hidrocefalia es un problema de salud frecuente en pediatría, en particular durante el primer mes de vida. La incidencia en América Latina es una de las más altas del mundo. En Colombia no existen datos representativos sobre la incidencia real de esta enfermedad. Recientes hallazgos relacionados con la dinámica del líquido cefalorraquídeo permitieron proponer nuevos modelos sobre la fisiopatología de la hidrocefalia que, junto con los hallazgos en la Resonancia Magnética, han llevado a tener una mejor comprensión de la enfermedad. El objetivo de este articulo es realizar una revisión de la información disponible en la literatura sobre los avances en la fisiopatología de la enfermedad y los hallazgos en neuroimágenes, además de realizar una breve revisión sobre el papel de estas en el diagnóstico y seguimiento de los pacientes. Se realizó una revisión bibliográfica con términos MeSH, en las bases de datos de PUBMED, OVID y SCOPUS con artículos publicados en los últimos 6 años, seleccionado un total de 30 artículos que abordaron el tema de forma integral. Los nuevos hallazgos descritos como lo son el sistema glinfático y el papel de las AQP4 y los avances en las neuroimágenes, sobre todo de la resonancia magnética, han ayudado a comprender mejor esta entidad, apoyando el desarrollo de un nuevo modelo de la dinámica del líquido cefalorraquídeo y a partir de él diferentes explicaciones sobre la fisiopatología. MÉD.UIS.2022;35(1): 17-29.

Abstract Hydrocephalus is a frequent health problem in pediatrics, particularly during the first month of life. The incidence in Latin America is one of the highest in the world. In Colombia there are no representative data. Recent findings related to the dynamics of cerebrospinal fluid allowed proposals of new models on the pathophysiology of hydrocephalus that, along with new findings on MRI, have led to a better understanding of the disease. The aim of this work is to review the information available in the literature about the progress in the pathophysiology of the disease and neuroimaging findings, in addition to conducting a brief review on the role of these in the diagnosis and follow-up of patients. A bibliographic review with MeSH terms was carried out in PUBMED, OVID and SCOPUS databases, with articles published in the last 6 years. 30 articles that dealt with the theme in a comprehensive way were included. New findings described as the glymphatic system and the role of AQP4, along with advances in neuroimaging, especially MRI, have helped to better understand hydrocephalus, supporting the development of a new model of cerebrospinal fluid dynamics, and based on it, different explanations regarding its pathophysiology. MÉD.UIS.2022;35(1): 17-29.

Síndrome Pos-COVID y Síndrome de Fatiga Crónica: ¿Dos caras de la misma moneda? / POST-COVID SYNDROME AND CHRONIC FATIGUE SYNDROME: TWO SIDES OF THE SAME COIN

El síndrome de fatiga crónica es una enfermedad caracterizada, principalmente, por la manifestación de la fatiga, el dolor muscular difuso, y alteraciones en el sueño, en un periodo de no menos de 6 meses y que no son explicables por alguna causa. Es llamativo que, luego de un periodo de tiempo de padecer la COVID-19, los pacientes presenten síntomas similares a los hallados en el síndrome de fatiga crónica. A esta afección se la denomino síndrome pos-COVID. Los virus son los principales sospechosos en la aparición de ambos síndromes, estos podrían ocasionar la generación de daño mitocondrial, una neuroinflamación, alteración en el sistema glinfático o la disfunción en el eje hipotálamo-pituitario-adrenal entre otros. Dichos mecanismos serían los implicados en la aparición de los síntomas que padecen los pacientes con estos síndromes. El objetivo de esta revisión literaria es analizar y describir los posibles mecanismos que explicarían la manifestación de los síntomas del síndrome de fatiga crónica en los pacientes que hayan sufrido la COVID-19. Hasta el momento no existen tratamientos totalmente efectivos para erradicar los síntomas en ambos síndromes. Dado el abanico de síntomas que padecen estos pacientes, el enfoque terapéutico debe ser interdisciplinario para tratar de mejorar su calidad de vida.

Atypical Virchow-Robin SpacesMimicking Cystic Primary Brain Tumor ­ Clinical Report and Literature Review

The Virchow-Robin spaces (VRSs), which are often incidentally observed in modern structural neuroimaging examinations, are small cystic cavities that usually surround the small arteries and arterioles at the level of basal ganglia, the anterior perforated substance and the thalamic-mesencephalic junction. Typically, they have similar physicochemical characteristics to cerebral spinal fluid (CSF) and there is no contrast enhancement on brain CT andMRI images. Its real meaning is unknown, although some contemporary studies have suggested that it might be related to certain traumatic brain injury or several other central nervous system (CNS) disorders, as degenerative diseases. Occasionally, some wide and atypical VRS may be mistaken for primary cystic brain tumors, especially in the context of large and symptomatic lesions, multiple clustered cysts, cortical lesions and if there is adjacent reactive gliosis. The present paper reports four patients who were affected by atypical VRS mimicking brain tumors that required imaging follow-up or even a biopsy to confirm the diagnosis or to indicate the correct approach. Although it is not so unusual, one of them occurred concomitantly and adjacent to a diffuse glioma (co-deleted 1p19q, WHO-GII).

The Glymphatic System: A Review

The brain represents 2% of the adult body mass; conversely, it is responsible for 20% to 25% of the glucose and 20% of the oxygen consumption, receiving 15% of the cardiac output. This substantial metabolic rate is associated with a significant production of biological debris, which is potentially toxic. Therefore, a complex and efficient clearance system is required to prevent the accumulation of byproducts and ensure optimal function. However, until today, there is little knowledge about this topic. The glymphatic system, also known as perivascular pathway, is a recently described glialdependent network that is responsible for the clearance of metabolites from the central nervous system (CNS), playing a role equivalent to the one played by the lymphatic vessels present in other organs. Studies have demonstrated that the glymphatic pathway has a paramount role in protein homeostasis, and that the malfunction of this system may be related to the development of neurodegenerative disorders such as Alzheimer disease and normal pressure hydrocephalus. They also showed that body posture, exercise and the state of consciousness influence the glymphatic transport. In this context, the understanding of this clearance system could not only clarify the pathophysiology of several diseases, but also contribute to future therapeutic interventions. In the present article, we will evaluate the glymphatic pathway, focusing on the factors that regulate its flow, as well as on its role in CNS physiology and in disease initiation and progression, including dementia, hydrocephalus, glaucoma and traumatic brain injury. Ultimately, this review also aims to encourage further research on novel therapeutic targets.