Metabolite Clearance During Wakefulness and Sleep

2017 ◽  
pp. 385-423 ◽  
Author(s):  
Stephen B. Hladky ◽  
Margery A. Barrand
Keyword(s):  
Metabolite Clearance

scholarly journals Strong Circadian Rhythms in the Choroid Plexus: Implications for Sleep-Independent Brain Metabolite Clearance

2018 ◽  
Vol 12 ◽  
pp. 117906951878376 ◽  
Author(s):  
Jihwan Myung ◽  
Dean Wu ◽  
Valérie Simonneaux ◽  
Timothy Joseph Lane
Keyword(s):  
Circadian Rhythms ◽  
Choroid Plexus ◽  
Brain Metabolite ◽  
Metabolite Clearance

scholarly journals Unraveling why we sleep: Quantitative analysis reveals abrupt transition from neural reorganization to repair in early development

2020 ◽  
Vol 6 (38) ◽  
pp. eaba0398 ◽  
Author(s):  
Junyu Cao ◽  
Alexander B. Herman ◽  
Geoffrey B. West ◽  
Gina Poe ◽  
Van M. Savage
Keyword(s):  
Quantitative Analysis ◽  
Early Development ◽  
Rem Sleep ◽  
Early Ontogeny ◽  
Evolutionary Constraints ◽  
Relative Importance ◽  
Complex Interplay ◽  
Neural Repair ◽  
Abrupt Transition ◽  
Metabolite Clearance

Sleep serves disparate functions, most notably neural repair, metabolite clearance and circuit reorganization. Yet the relative importance remains hotly debated. Here, we create a novel mechanistic framework for understanding and predicting how sleep changes during ontogeny and across phylogeny. We use this theory to quantitatively distinguish between sleep used for neural reorganization versus repair. Our findings reveal an abrupt transition, between 2 and 3 years of age in humans. Specifically, our results show that differences in sleep across phylogeny and during late ontogeny (after 2 or 3 years in humans) are primarily due to sleep functioning for repair or clearance, while changes in sleep during early ontogeny (before 2 or 3 years) primarily support neural reorganization and learning. Moreover, our analysis shows that neuroplastic reorganization occurs primarily in REM sleep but not in NREM. This developmental transition suggests a complex interplay between developmental and evolutionary constraints on sleep.

scholarly journals Functional hyperemia drives fluid exchange in the paravascular space

2020 ◽  
Author(s):  
Ravi Kedarasetti ◽  
Kevin L. Turner ◽  
Christina Echagarruga ◽  
Bruce J. Gluckman ◽  
Patrick J. Drew ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Brain Tissue ◽  
Functional Hyperemia ◽  
Fluid Exchange ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Metabolite Clearance ◽  
Pressure Changes ◽  
The Brain ◽  
Paravascular Space

Abstract The brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that fluid movement through the arteriolar paravascular space (PVS) promotes metabolite clearance. We performed simulations to understand how arteriolar pulsations and dilations, and brain deformability affect PVS fluid flow. In simulations with compliant brain tissue, arteriolar pulsations did not drive appreciable flows in the PVS. However, when the arteriole dilated as in functional hyperemia, there was a marked movement of fluid. Simulations suggest that functional hyperemia may also serve to increase fluid exchange between the PVS and the subarachnoid space. We measured blood vessels and brain tissue displacement simultaneously in awake, head-fixed mice using two-photon microscopy. These measurements showed that brain deforms in response to pressure changes in PVS, as predicted by simulations. Our results show that the deformability of the brain tissue needs to be accounted for when studying fluid flow and metabolite transport.Acknowledgements: This work was supported by NSF Grant CBET 1705854.

scholarly journals Arterial pulsations drive oscillatory flow of CSF but not directional pumping

2020 ◽  
Author(s):  
Ravi Teja Kedarasetti ◽  
Patrick J. Drew ◽  
Francesco Costanzo
Keyword(s):  
Oscillatory Flow ◽  
Fluid Dynamic ◽  
Cerebral Blood Vessels ◽  
Csf Flow ◽  
Dynamic Simulations ◽  
Naturally Occurring ◽  
Peristaltic Pumping ◽  
Convective Exchange ◽  
Metabolite Clearance ◽  
The Brain

AbstractThe brain lacks a traditional lymphatic system for metabolite clearance. The existence a “glymphatic system” where metabolites are removed from the brain’s extracellular space by convective exchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) along the paravascular spaces (PVS) around cerebral blood vessels has been controversial for nearly a decade. While recent work has shown clear evidence of directional flow of CSF in the PVS in anesthetized mice, the driving force for the observed fluid flow remains elusive. The heartbeat-driven peristaltic pulsation of arteries has been proposed as a probable driver of directed CSF flow. In this study, we use rigorous fluid dynamic simulations to provide a physical interpretation for peristaltic pumping of fluids. Our simulations match the experimental results and show that arterial pulsations only drive oscillatory motion of CSF in the PVS. The observed directional CSF flow can be explained by naturally occurring and/or experimenter-generated pressure differences.

scholarly journals Functional hyperemia drives fluid exchange in the paravascular space

2020 ◽  
Author(s):  
Ravi Kedarasetti ◽  
Kevin L. Turner ◽  
Christina Echagarruga ◽  
Bruce J. Gluckman ◽  
Patrick J. Drew ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Brain Tissue ◽  
Functional Hyperemia ◽  
Fluid Exchange ◽  
Fluid Movement ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Metabolite Clearance ◽  
The Brain ◽  
Paravascular Space

Abstract The brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that fluid movement through the arterial paravascular space (PVS) promotes metabolite clearance. We performed simulations to understand how arterial pulsations and dilations, and brain deformability affect PVS fluid flow. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. However, when the artery dilated as in functional hyperemia, there was a marked movement of fluid. Simulations suggest that functional hyperemia may also serve to increase fluid exchange between the PVS and the subarachnoid space. We measured blood vessels and brain tissue displacement simultaneously in awake, head-fixed mice using two-photon microscopy. Measurements show that brain deforms in response to fluid movement in PVS, as predicted by simulations. Our results show that the deformability of the brain tissue needs to be accounted for when studying fluid flow and metabolite transport.

Brain metabolite clearance: impact on Alzheimer’s disease

2014 ◽  
Vol 29 (3) ◽  
pp. 553-561 ◽  
Author(s):  
Juan M. Zolezzi ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Metabolite ◽  
Metabolite Clearance
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