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 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

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 ◽  
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.

Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh
Keyword(s):  
Rat Brain ◽  
Brain Tissue ◽  
Molecularly Imprinted Polymer ◽  
Lipid Emulsion ◽  
Limit Of Detection ◽  
Imprinted Polymer ◽  
Toxic Dose ◽  
Molecularly Imprinted ◽  
The Brain ◽  
Rat Brain Tissue

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

scholarly journals High-fat diet-induced obesity and impairment of brain neurotransmitter pool

2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Tissue ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Obese Group ◽  
Control Group ◽  
High Fat ◽  
Brain Neurotransmitter ◽  
The Brain ◽  
Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

scholarly journals Effect of Xenon Treatment on Gene Expression in Brain Tissue after Traumatic Brain Injury in Rats

2021 ◽  
Vol 11 (7) ◽  
pp. 889
Author(s):  
Anton D. Filev ◽  
Denis N. Silachev ◽  
Ivan A. Ryzhkov ◽  
Konstantin N. Lapin ◽  
Anastasiya S. Babkina ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Target Genes ◽  
Neural Function ◽  
Stress Genes ◽  
Expression Of Genes ◽  
Delayed Recovery ◽  
The Brain ◽  
Lower Expression

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.

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