scholarly journals Functional hyperemia drives fluid exchange in the paravascular space

2019 ◽  
Author(s):  
Ravi Teja Kedarasetti ◽  
Kevin L. Turner ◽  
Christina Echagarruga ◽  
Bruce G. Gluckman ◽  
Patrick J. Drew ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Brain Tissue ◽  
Functional Hyperemia ◽  
Fluid Exchange ◽  
Fluid Movement ◽  
Two Photon Microscopy ◽  
Measured Displacement ◽  
And Function ◽  
The Brain ◽  
Paravascular Space

AbstractMaintaining the ionic and chemical composition of the extracellular spaces in the brain is extremely important for its health and function. However, the brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that the fluid movement through the paravascular space (PVS) surrounding penetrating arteries can help remove metabolites from the brain. The dynamics of fluid movement in the PVS and its interaction with arterial dilation and brain mechanics are not well understood. Here, we performed simulations to understand how arterial pulsations and dilations interact with brain deformability to drive fluid flow in the PVS. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. In contrast, when the artery dilated with dynamics like those seen during functional hyperemia, there was a marked movement of fluid through the PVS. Our simulations suggest that in addition to its other purposes, functional hyperemia may serve to increase fluid exchange between the PVS and the subarachnoid space, improving the clearance of metabolic waste. We measured displacement of the blood vessels and the brain tissue simultaneously in awake, head-fixed mice using two-photon microscopy. Our measurements show that brain tissue can deform in response to fluid movement in the PVS, as predicted by simulations. The results from our simulations and experiments show that the deformability of the soft brain tissue needs to be accounted for when studying fluid flow and metabolite transport in the brain.

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.

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 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):  
Brain Tissue ◽  
Functional Hyperemia ◽  
Csf Flow ◽  
Fluid Exchange ◽  
Two Photon Microscopy ◽  
Arteriolar Wall ◽  
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 directional fluid movement through the arteriolar paravascular space (PVS) promotes metabolite clearance. We performed simulations to examine if arteriolar pulsations and dilations can drive directional CSF flow in the PVS and found that arteriolar wall movements do not drive directional CSF flow. We propose an alternative method of metabolite clearance from the PVS, namely fluid exchange between the PVS and the subarachnoid space (SAS). In simulations with compliant brain tissue, arteriolar pulsations did not drive appreciable fluid exchange between the PVS and the SAS. However, when the arteriole dilated, as seen during functional hyperemia, there was a marked exchange of fluid. Simulations suggest that functional hyperemia may serve to increase metabolite clearance from the PVS. 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, consistent with our 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 vasodilation drives convective fluid flow in the brain: a poroelastic model

2021 ◽  
Author(s):  
Ravi Kedarasetti ◽  
Patrick J. Drew ◽  
Francesco Costanzo
Keyword(s):  
Brain Tissue ◽  
Convective Flow ◽  
Extracellular Volume ◽  
Fluid Movement ◽  
Flow Through ◽  
Poroelastic Model ◽  
Sensory Evoked ◽  
Convective Fluid ◽  
The Brain ◽  
Paravascular Space

The movement of fluid into, through, and out of the brain plays an important role in clearing metabolic waste. However, there is controversy regarding the mechanisms driving fluid movement, and whether the movement metabolic waste is primarily driven by diffusion or convection. The dilation of penetrating arterioles in the brain in response to increases in neural activity (neurovascular coupling) is an attractive candidate for driving fluid circulation, as it drives deformation of the brain tissue and of the paravascular space around arteries, resulting in fluid movement. We simulated the effects of vasodilation on fluid movement into and out of the brain using a novel poroelastic model of brain tissue. We found that arteriolar dilations could drive convective flow through the brain radially outward from the arteriole, and that this flow is sensitive to the dynamics of the dilation. Simulations of sleep-like conditions, with larger vasodilations and increased extracellular volume in the brain showed enhanced movement of fluid from the paravascular space into the brain. Our simulations suggest that both sensory-evoked and sleep-related arteriolar dilations can drive convective flow of cerebrospinal fluid from the paravascular space into the brain tissue around arterioles.

scholarly journals Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice

2022 ◽  
Vol 23 (2) ◽  
pp. 629
Author(s):  
Xiangli Zhao ◽  
Sadaf Hasan ◽  
Benjamin Liou ◽  
Yi Lin ◽  
Ying Sun ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Brain Tissue ◽  
Clinical Settings ◽  
Progressive Degeneration ◽  
Disease Modifying Therapies ◽  
Β Amyloid ◽  
And Function ◽  
The Brain ◽  
Deficient Mice

Neurodegenerative diseases are debilitating impairments that affect millions of people worldwide and are characterized by progressive degeneration of structure and function of the central or peripheral nervous system. Effective biomarkers for neurodegenerative diseases can be used to improve the diagnostic workup in the clinic as well as facilitate the development of effective disease-modifying therapies. Progranulin (PGRN) has been reported to be involved in various neurodegenerative disorders. Hence, in the current study we systematically compared the inflammation and accumulation of typical neurodegenerative disease markers in the brain tissue between PGRN knockout (PGRN KO) and wildtype (WT) mice. We found that PGRN deficiency led to significant neuron loss as well as activation of microglia and astrocytes in aged mice. Several characteristic neurodegenerative markers, including α-synuclein, TAR DNA-binding protein 43 (TDP-43), Tau, and β-amyloid, were all accumulated in the brain of PGRN-deficient mice as compared to WT mice. Moreover, higher aggregation of lipofuscin was observed in the brain tissue of PGRN-deficient mice compared with WT mice. In addition, the autophagy was also defective in the brain of PGRN-deficient mice, indicated by the abnormal expression level of autophagy marker LC3-II. Collectively, comprehensive assays support the idea that PGRN plays an important role during the development of neurodegenerative disease, indicating that PGRN might be a useful biomarker for neurodegenerative diseases in clinical settings.

scholarly journals Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

2020 ◽  
Vol 8 ◽  
Author(s):  
Yu Rim Kim ◽  
Young Min Kim ◽  
Jaeho Lee ◽  
Joohyun Park ◽  
Jong Eun Lee ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Neutrophil Infiltration ◽  
Two Photon ◽  
Activated State ◽  
The Central Nervous System ◽  
Time Observation ◽  
And Function ◽  
The Brain

The circulatory neutrophil and brain tissue-resident microglia are two important immune cells involved in neuroinflammation. Since neutrophils that infiltrate through the brain vascular vessel may affect the immune function of microglia in the brain, close investigation of the interaction between these cells is important in understanding neuroinflammatory phenomena and immunological aftermaths that follow. This study aimed to observe how morphology and function of both neutrophils and microglia are converted in the inflamed brain. To directly investigate cellular responses of neutrophils and microglia, LysMGFP/+ and CX3CR1GFP/+ mice were used for the observation of neutrophils and microglia, respectively. In addition, low-dose lipopolysaccharide (LPS) was utilized to induce acute inflammation in the central nervous system (CNS) of mice. Real-time observation on mice brain undergoing neuroinflammation via two-photon intravital microscopy revealed various changes in neutrophils and microglia; namely, neutrophil infiltration and movement within the brain tissue increased, while microglia displayed morphological changes suggesting an activated state. Furthermore, neutrophils seemed to not only actively interact with microglial processes but also exhibit reverse transendothelial migration (rTEM) back to the bloodstream. Thus, it may be postulated that, through crosstalk with neutrophils, macrophages are primed to initiate a neuroinflammatory immune response; also, during pathogenic events in the brain, neutrophils that engage in rTEM may deliver proinflammatory signals to peripheral organs outside the brain. Taken together, these results both show that neuroinflammation results in significant alterations in neutrophils and microglia and lay the pavement for further studies on the molecular mechanisms behind such changes.

scholarly journals Functional hyperemia drives fluid exchange in the paravascular space

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ravi Teja Kedarasetti ◽  
Kevin L. Turner ◽  
Christina Echagarruga ◽  
Bruce J. Gluckman ◽  
Patrick J. Drew ◽  
...  
Keyword(s):  
Functional Hyperemia ◽  
Fluid Exchange ◽  
Paravascular Space

scholarly journals Defining Hypoperfusion in Chronic Aphasia: An Individualized Thresholding Approach

2021 ◽  
Vol 11 (4) ◽  
pp. 491
Author(s):  
Noelle T. Abbott ◽  
Carolyn J. Baker ◽  
Conan Chen ◽  
Thomas T. Liu ◽  
Tracy E. Love
Keyword(s):  
Brain Tissue ◽  
Language Impairment ◽  
Valuable Insight ◽  
Functionally Impaired ◽  
Brain Structure And Function ◽  
Chronic Aphasia ◽  
And Function ◽  
The Relationship ◽  
The Brain ◽  
Post Onset

Within the aphasia literature, it is common to link location of lesioned brain tissue to specific patterns of language impairment. This has provided valuable insight into the relationship between brain structure and function, but it does not capture important underlying alterations in function of regions that remain structurally intact. Research has demonstrated that in the chronic stage of aphasia, variable patterns of reduced cerebral blood flow (CBF; hypoperfusion) in structurally intact regions of the brain contribute to persisting language impairments. However, one consistent issue in this literature is a lack of clear consensus on how to define hypoperfusion, which may lead to over- or underestimation of tissue functionality. In the current study, we conducted an exploratory analysis in six individuals with chronic aphasia (>1 year post-onset) using perfusion imaging to (1) suggest a new, individualized metric for defining hypoperfusion; (2) identify the extent of hypoperfused tissue in perilesional bands; and (3) explore the relationship between hypoperfusion and language impairment. Results indicated that our individualized metric for defining hypoperfusion provided greater precision when identifying functionally impaired tissue and its effects on language function in chronic aphasia. These results have important implications for intervention approaches that target intact (or impaired) brain tissue.

scholarly journals Simultaneous Quantification of 25-Hydroxyvitamin D3and 24,25-Dihydroxyvitamin D3in Rats Shows Strong Correlations between Serum and Brain Tissue Levels

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Xue ◽  
Xin He ◽  
Huan-De Li ◽  
Yang Deng ◽  
Miao Yan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Brain Tissue ◽  
High Performance ◽  
Serum Vitamin ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Serum Vitamin D ◽  
Liquid Chromatography Tandem Mass ◽  
And Function ◽  
The Brain

While vitamin D3is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3metabolites in the brain tissue is still lacking, and the relationship of vitamin D3status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3(25(OH)D3) and 24,25-dihydroxyvitamin D3(24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3metabolites could affect vitamin D3metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3and 24,25(OH)2D3in animal brain tissue. Vitamin D3metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3diet. There was also a strong correlation of vitamin D3metabolites in serum and brain. These results indicate that vitamin D3status in serum affects bioavailability of vitamin D3metabolites in the brain.

Ultrastructure of developing visual cortical synapses in the cat superior colliculus

1991 ◽  
Vol 49 ◽  
pp. 156-157
Author(s):  
Caroline A. Miller ◽  
Laura L. Bruce
Keyword(s):  
Superior Colliculus ◽  
Phosphate Buffer ◽  
Receptive Fields ◽  
Visual Cortical Area ◽  
Cortical Synapses ◽  
Visual Cortical ◽  
And Function ◽  
Phosphate Buffered Saline ◽  
The Brain ◽  
Cat Superior Colliculus

The first visual cortical axons arrive in the cat superior colliculus by the time of birth. Adultlike receptive fields develop slowly over several weeks following birth. The developing cortical axons go through a sequence of changes before acquiring their adultlike morphology and function. To determine how these axons interact with neurons in the colliculus, cortico-collicular axons were labeled with biocytin (an anterograde neuronal tracer) and studied with electron microscopy.Deeply anesthetized animals received 200-500 nl injections of biocytin (Sigma; 5% in phosphate buffer) in the lateral suprasylvian visual cortical area. After a 24 hr survival time, the animals were deeply anesthetized and perfused with 0.9% phosphate buffered saline followed by fixation with a solution of 1.25% glutaraldehyde and 1.0% paraformaldehyde in 0.1M phosphate buffer. The brain was sectioned transversely on a vibratome at 50 μm. The tissue was processed immediately to visualize the biocytin.

Sign in / Sign up

Export Citation Format

Share Document