Spatially Organized Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

2018 ◽  
Author(s):  
Emilie W. Olstad ◽  
Christa Ringers ◽  
Adinda Wens ◽  
Jan N. Hansen ◽  
Cecilia Brandt ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Cerebrospinal Fluid Flow ◽  
Ciliary Beating ◽  
The Brain

scholarly journals Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

2019 ◽  
Vol 29 (2) ◽  
pp. 229-241.e6 ◽  
Author(s):  
Emilie W. Olstad ◽  
Christa Ringers ◽  
Jan N. Hansen ◽  
Adinda Wens ◽  
Cecilia Brandt ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Cerebrospinal Fluid Flow ◽  
Ciliary Beating ◽  
The Brain

scholarly journals A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice

2020 ◽  
Vol 13 (10) ◽  
pp. dmm045344
Author(s):  
Zakia Abdelhamed ◽  
Marshall Lukacs ◽  
Sandra Cindric ◽  
Heymut Omran ◽  
Rolf W. Stottmann
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Primary Ciliary Dyskinesia ◽  
Human Condition ◽  
Central Pair ◽  
Cerebrospinal Fluid Flow ◽  
Hypomorphic Allele ◽  
Motile Cilia ◽  
The Brain ◽  
Ciliary Dyskinesia

ABSTRACTPrimary ciliary dyskinesia (PCD) is a human condition of dysfunctional motile cilia characterized by recurrent lung infection, infertility, organ laterality defects and partially penetrant hydrocephalus. We recovered a mouse mutant from a forward genetic screen that developed many of the hallmark phenotypes of PCD. Whole-exome sequencing identified this primary ciliary dyskinesia only (Pcdo) allele to be a nonsense mutation (c.5236A>T) in the Spag17 coding sequence creating a premature stop codon (K1746*). The Pcdo variant abolished several isoforms of SPAG17 in the Pcdo mutant testis but not in the brain. Our data indicate differential requirements for SPAG17 in different types of motile cilia. SPAG17 is essential for proper development of the sperm flagellum and is required for either development or stability of the C1 microtubule structure within the central pair apparatus of the respiratory motile cilia, but not the brain ependymal cilia. We identified changes in ependymal ciliary beating frequency, but these did not appear to alter lateral ventricle cerebrospinal fluid flow. Aqueductal stenosis resulted in significantly slower and abnormally directed cerebrospinal fluid flow, and we suggest that this is the root cause of the hydrocephalus. The Spag17Pcdo homozygous mutant mice are generally viable to adulthood but have a significantly shortened lifespan, with chronic morbidity. Our data indicate that the c.5236A>T Pcdo variant is a hypomorphic allele of Spag17 that causes phenotypes related to motile, but not primary, cilia. Spag17Pcdo is a useful new model for elucidating the molecular mechanisms underlying central pair PCD pathogenesis in the mouse.This article has an associated First Person interview with the first author of the paper.

scholarly journals Paravascular spaces at the brain surface: Low resistance pathways for cerebrospinal fluid flow

2017 ◽  
Vol 38 (4) ◽  
pp. 719-726 ◽  
Author(s):  
Beatrice Bedussi ◽  
Mitra Almasian ◽  
Judith de Vos ◽  
Ed VanBavel ◽  
Erik NTP Bakker
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Confocal Imaging ◽  
Waste Products ◽  
Cerebrospinal Fluid Flow ◽  
Low Resistance ◽  
Cranial Window ◽  
Brain Surface ◽  
Antegrade Flow ◽  
The Brain

Clearance of waste products from the brain is of vital importance. Recent publications suggest a potential clearance mechanism via paravascular channels around blood vessels. Arterial pulsations might provide the driving force for paravascular flow, but its flow pattern remains poorly characterized. In addition, the relationship between paravascular flow around leptomeningeal vessels and penetrating vessels is unclear. In this study, we determined blood flow and diameter pulsations through a thinned-skull cranial window. We observed that microspheres moved preferentially in the paravascular space of arteries rather than in the adjacent subarachnoid space or around veins. Paravascular flow was pulsatile, generated by the cardiac cycle, with net antegrade flow. Confocal imaging showed microspheres distributed along leptomeningeal arteries, while their presence along penetrating arteries was limited to few vessels. These data suggest that paravascular spaces around leptomeningeal arteries form low resistance pathways on the surface of the brain that facilitate cerebrospinal fluid flow.

scholarly journals Interstitial and cerebrospinal fluid exchanging process revealed by phase alternate labeling with null recovery MRI

2021 ◽  
Author(s):  
Anna M Li ◽  
Jiadi Xu
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Interstitial Fluid Flow ◽  
Cerebrospinal Fluid Flow ◽  
Recovery Curves ◽  
Ependymal Layer ◽  
Apparent Diffusion ◽  
The Difference ◽  
The Brain

Purpose: To develop Phase Alternate LAbeling with Null recovery (PALAN) MRI methods for the quantification of interstitial to cerebrospinal fluid flow (ICF) and cerebrospinal to interstitial fluid flow (CIF) in the brain. Method: In both T1-PALAN and apparent diffusion coefficient (ADC)-PALAN MRI methods, the cerebrospinal fluid (CSF) signal was nulled, while the residual interstitial fluid (ISF) was labeled by alternating the phase of pulses. ICF was extracted from the difference between the recovery curves of CSF with and without labeling. Similarly, CIF was measured by the T2-PALAN MRI method by labeling CSF, which took advance of the significant T2 difference between CSF and parenchyma. Results: Both T1-PALAN and ADC-PALAN observed a rapid occurrence of ICF at 67±56 ms and 13±2 ms interstitial fluid transit times, respectively. ICF signal peaked at 1.5 s for both methods. ICF was 1153±270 ml/100ml/min with T1-PALAN in the third and lateral ventricles, which was higher than 891±60 ml/100ml/min obtained by ADC-PALAN. The results of the T2-PALAN suggested the ISF exchanging from ependymal layer to the parenchyma was extremely slow. Conclusion: The PALAN methods are suitable tools to study ISF and CSF flow kinetics in the brain.

Network Analysis of Cerebrospinal Fluid Dynamics

2001 ◽  
Author(s):  
Lili Zheng ◽  
Michael Egnor ◽  
Keith Banninger
Keyword(s):  
Fluid Dynamics ◽  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Network Analysis ◽  
Progressive Increase ◽  
Cerebrospinal Fluid Dynamics ◽  
High Failure Rate ◽  
Cerebrospinal Fluid Flow ◽  
Life Threatening ◽  
The Brain

Abstract Hydrocephalus is a group of life threatening disorders of cerebrospinal fluid flow in and around the brain. It is characterized, in most cases, by accumulation of cerebrospinal fluid in the ventricles of the brain and a progressive increase in pressure in the cranium. The etiology has traditionally been ascribed to an imbalance between the formation and absorption of the cerebrospinal fluid (CSF). Based on this understanding, the treatment is to insert a shunt surgically in order to drain the accumulating fluid in the heart or abdomen. This treatment is invasive and has a high failure rate.

scholarly journals Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain

2018 ◽  
Vol 137 (1) ◽  
pp. 151-165 ◽  
Author(s):  
Qiaoli Ma ◽  
Miriam Ries ◽  
Yann Decker ◽  
Andreas Müller ◽  
Chantal Riner ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Cerebrospinal Fluid Flow ◽  
The Brain

scholarly journals Shear-Induced Amyloid Aggregation in the Brain: V. Are Alzheimer’s and Other Amyloid Diseases Initiated in the Lower Brain and Brainstem by Cerebrospinal Fluid Flow Stresses?

2020 ◽  
pp. 1-24
Author(s):  
Conrad N. Trumbore
Keyword(s):  
Cerebrospinal Fluid ◽  
Conformational Changes ◽  
Extensional Flow ◽  
Amyloid Β ◽  
High Energy ◽  
Mechanical Agitation ◽  
Cerebrospinal Fluid Flow ◽  
Pulse Waves ◽  
Amyloid Diseases ◽  
The Brain

Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.

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