Assessment of factors influencing glymphatic activity and implications for clinical medicine

The glymphatic system is a highly specialized fluid transport system in the central nervous system. It enables the exchange of the intercellular fluid of the brain, regulation of the movement of this fluid, clearance of unnecessary metabolic products, and, potentially, brain immunity. In this review, based on the latest scientific reports, we present the mechanism of action and function of the glymphatic system and look at the role of factors influencing its activity. Sleep habits, eating patterns, coexisting stress or hypertension, and physical activity can significantly affect glymphatic activity. Modifying them can help to change lives for the better. In the next section of the review, we discuss the connection between the glymphatic system and neurological disorders. Its association with many disease entities suggests that it plays a major role in the physiology of the whole brain, linking many pathophysiological pathways of individual diseases

Importance of CSF circulation following ischaemic stroke: A novel MRI investigation of CSF parenchymal flow

It has been proposed that intracranial pressure (ICP) elevation and collateral failure are responsible for unexplained early neurological deterioration (END) in stroke. Our aim was to investigate whether cerebrospinal fluid (CSF) dynamics, rather than oedema, are responsible for elevation of ICP after ischaemic stroke. Permanent middle cerebral artery occlusion (pMCAO) was induced with an intraluminal filament. At 24 hours after stroke, baseline ICP was measured, and CSF dynamics were probed via a steady-state infusion method. For the first time, we found a significant correlation between the baseline ICP at 24 hours post-stroke and the value of CSF outflow resistance. Results show that CSF outflow resistance, rather than oedema, was the mechanism responsible for ICP elevation following ischaemic stroke. This challenges current concepts and suggests the possibility that intracranial hypertension may be occurring undetected in a much wider range of stroke patients than is currently considered to be the case. Over the last decade, there has been significant renewed interest in the anatomical pathways and physiological mechanisms for the circulation of CSF. The glymphatic system is one such pathway that has been recently characterised. This network drives CSF into the brain along periarterial spaces and interstitial fluid (ISF) out along perivenous spaces. Aquaporin-4 (AQP4) water channels, densely expressed at the vascular endfeet of astrocytes, facilitate glymphatic transport. Glymphatic failure has been linked to a broad range of neurodegenerative diseases including ischaemic stroke. Accordingly, if the glymphatic circulation is a major outflow route for CSF, glymphatic dysfunction following ischaemic stroke could alter CSF dynamics and, therefore, ICP. Nevertheless, the glymphatic hypothesis is still controversial. All in vivo and biomechanical modelling studies that have investigated the glymphatic system have been based on utilizing a solute tracer to track the movement of CSF within the intracranial space. Since 99% of CSF is water, it is questionable whether nonwater tracer molecules can ever show the real dynamic flow of CSF. Hence, we sought the develop of a new MRI method to directly image CSF dynamics in-vivo, by exploiting an isotopically enriched MRI tracer, namely, H217O. Our results reveal glymphatic flow that is dramatically faster and more extensive than previously thought. Moreover, we confirm the critical role of aquaporin-4 (AQP4) channels in glymphatic flow by imaging CSF water dynamics in the brain using H217O alongside a potent blocker of AQP4. We hope in future that this new method can be used to investigate the responsible mechanism for the increased CSF resistance and ICP elevation following ischaemic stroke

Νέες υποθέσεις, για την παραγωγή, κυκλοφορία και απορρόφηση του εγκεφαλονωτιαίου υγρού

Η διπλωματική έχει ως θεματική, τις νέες υποθέσεις που υπάρχουν στην παραγωγή, κυκλοφορία και απορρόφηση του εγκεφαλονωτιαίου υγρού (ΕΝΥ). Για αυτό τον σκοπό, πραγματοποιήθηκε μια συστηματική ανασκόπηση της βιβλιογραφίας και έχουν συμπεριληφθεί μελέτες βασικής και κλινικής έρευνας. Στο πρώτο μέρος συζητιέται ο φυσιολογικός ρόλος του ΕΝΥ. Συγκεκριμένα, ο βαθμός και μηχανισμός παραγωγής του ΕΝΥ από τα χορειοδή πλέγματα αλλά και από άλλα σημεία, η κυκλοφορία του ΕΝΥ, η σχέση του με το διάμεσο υγρό (intersistial fluid), μεταξύ των νευρώνων και των γλοιικών κυττάρων, του συστήματος της γλοίμφου (glymphatic) και η συμμετοχή του στην εκκαθάριση μεταβολικών προϊόντων και αποβλήτων από το Κεντρικό Νευρικό Σύστημα. Επίσης, συζητιέται η συσχέτιση λειτουργίας του ΕΝΥ με το τον κύκλο ύπνου-εγρήγορσης, η ύπαρξη μηνιγγικών λεμφαγγείων, ο ρόλος των περινευρικών χώρων των εγκεφαλικών συζυγιών και νωτιαίων νεύρων ως κύριο μέσου παροχέτευσης, και η αλληλεπίδραση με άλλες μεταβλητές και λειτουργίες όπως η ενδοκράνια πίεση και το ανοσοποιητικό σύστημα. Το δεύτερο μέρος αναφέρεται στον ρόλο του ΕΝΥ σε παθοφυσιολογικές καταστάσεις. Συγκεκριμένα, στην διερεύνηση των ευρημάτων σε ασθένειες της νευροχειρουργικής και της νευρολογίας καθώς και η πιθανή συμβολή του στην διαγνωστική μέσω βιοδεικτών και νευροαπεικονιστική. Τέλος, εξετάζονται τα νεότερα δεδομένα στην έρευνα του ΕΝΥ και συζητιούνται τα εκκρεμή ερωτήματα, ταυτόχρονα λαμβάνοντας υπόψη τις μελλοντικές κατευθύνσεις στην έρευνα του ΕΝΥ.This thesis discusses the newest findings related to the life cycle of cerebrospinal fluid (CSF)- its production, its circulation and its absorption. For this purpose, a systematic review of the literature was performed and basic and clinical research studies have been included. In the first part, the physiologica role of CSF is discussed. Specifically, the degree and mechanisms of CSF production from the choroid plexus but also other brain areas, CSF circulation, its intimate relationship with the interstitial fluid between the neurons and the glia, the role of the glymphatic system and its participation in metabolite and waste clearance from the Central Nervous System. Also discussed is the association of CSF function with the sleep-wake cycle, the existence of meningeal lymphatics, the role of the perineural spaces of the cerebral cortex and spinal nerves as the main drainage system, and their interaction with other variables including intracranial pressure and the immune system. In the second part, the role of CSF in pathophysiological conditions is discussed. Specifically, the role of CSF in neurological diseases and neurosurgery cases as well as its contribution to diagnosis as a source of biomarkers and via neuroimaging. Finally, new frontiers in CSF research are examined and outstanding questions and the future directions of CSF research are considered

Landmarks and frontiers in biological fluid dynamics

Biological systems are influenced by fluid mechanics at nearly all spatiotemporal scales. This broad relevance of fluid mechanics to biology has been increasingly appreciated by engineers and biologists alike, leading to continued expansion of research in the field of biological fluid dynamics. While this growth is exciting, it can present a barrier to researchers seeking a concise introduction to key challenges and opportunities for progress in the field. Rather than attempt a comprehensive review of the literature, this article highlights a limited selection of classic and recent work. In addition to motivating the study of biological fluid dynamics in general, the goal is to identify both longstanding and emerging conceptual questions that can guide future research. Answers to these fluid mechanics questions can lead to breakthroughs in our ability to predict, diagnose, and correct biological dysfunction, while also inspiring a host of new engineering technologies

Cerebrospinal Fluid

Cerebrospinal fluid is an essential, clear, and colorless liquid essential for maintaining homeostasis of the brain and neuronal functioning. Its secretion in adults ranges from 400 to 600 ml per day and it is renewed about four or five times daily. Cerebrospinal fluid is mainly reabsorbed from arachnoid granulations. Any disruption in this well-regulated system, such as overproduction, decreased absorption, or obstruction, could lead to hydrocephalus. This book contains essential knowledge about cerebrospinal fluid anatomy and physiology, pathologies related to cerebrospinal fluid, and treatment strategies for cerebrospinal fluid disorders

Sleep dependent memory consolidation in mild cognitive impairment subtypes

Sleep plays a crucial role in the overnight consolidation of newly learnt information in young adults, however the sleep-memory relationship in older adults is less understood. Age-associated memory decline as well as sleep disturbances are a concern for up to 60% of older people. Greater non-rapid eye movement (NREM) sleep neurophysiology such as slow waves and spindles have been postulated to be important for overnight memory consolidation, however, these associations are unclear in those at greater risk of dementia, namely in Mild Cognitive Impairment (MCI). Furthermore, it is unclear whether structural brain integrity for regions important for sleep and memory in ageing such as the hippocampus and medial prefrontal cortex, are associated with OMC in this ‘at-risk’ population. The overall aims of this study were to determine if there are differences in memory consolidation in older adults with and without MCI (and their subtypes), and examine associations between overnight memory consolidation with NREM sleep neurophysiology, and structural brain integrity using neuroimaging. Using a 256-channel high density EEG and a novel task of spatial navigation memory, the implications of these findings speak to the design of clinical trials targeting sleep in older adults, to determine the impact and functions of sleep as a modifiable risk factor for cognitive decline

11th European Headache Federation Congress jointly with 31st Congress of the Italian Society for the Study of Headaches : Rome, Italy. 01-03 December 2017

. Aims of the study were explore the relationship between peripheral chromatic and central visual dysfunction evaluating also the presence of functional receptor impairment in patients with migraine, with and without aura examined interictally