Brain Fluid Channels for Metabolite Removal

Abstract

The adult human brain represents only 2 % of the body's total weight, however it is one of the most metabolically active organs in the mammalian body. Its high metabolic activity necessitates an efficacious waste clearance system. Besides the blood, there are two fluids closely linked to the brain and spinal cord drainage system: interstitial fluid (ISF) and cerebrospinal fluid (CSF). The aim of this review is to summarize the latest research clarifying the channels of metabolite removal by fluids from brain tissue, subarachnoid space (SAS) and brain dura (BD). Special attention is focused on lymphatic vascular structures in the brain dura, their localizations within the meninges, morphological properties and topographic anatomy. The review ends with an account of the consequences of brain lymphatic drainage failure. Knowledge of the physiological state of the clearance system is crucial in order to understand the changes related to impaired brain drainage.

Reactive Cu2+-peptide intermediates revealed by kinetic studies gain relevance by matching time windows in copper metallomics

“…In a strikingly close analogy to the emerging picture of Cu(II) interactions with albumin in blood, the Cu(II) complexes of Aβ 4 – 42 and Aβ 4 – 40 peptides were detected in the CSF by mass spectrometry. 79 Only the 4N ATCUN/NTS complex is sufficiently inert in ESI-MS experimental conditions to be detected, 5 and CSF is the drain for the synaptic fluid, 98 hence Cu(II)/Aβ 4 – x can migrate there from the neuronal pathways in the cortex and hippocampus, having enough time to form the kinetically inert 4N species in the process. As discussed before, such species are well suited for protecting the brain from copper-generated ROS.…”

Intracranial Gene Delivery Mediated by Albumin-Based Nanobubbles and Low-Frequency Ultrasound

“…Several novel CSF/interstitial fluid excretory pathways have been discovered, including the olfactory route for cerebrospinal fluid drainage into the peripheral lymphatic [66,67], intramural periarterial drainage (IPAD), and glymphatic drainage systems in recent years [68]. Our results suggest that the dye or gene reached the nasal and cranial cavity through these pathways.…”