Fluids and flows in brain cancer and neurological disorders

Jin, Peng; Munson, Jennifer M.

doi:10.1002/wsbm.1582

Cited by 5 publications

(3 citation statements)

References 144 publications

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“…O 2 and CO 2 are crucial biomarkers for energy metabolism in living organisms. Conditions like hypoxia and/or elevated CO 2 levels caused by hydrocephalus, brain tumors, and respiratory failure can lead to severe cellular and organ damage . The prevalence of diabetes is reaching epidemic levels, giving rise to various complications like microangiopathy, atherosclerosis, coronary heart disease, peripheral vascular disease, peripheral vascular disease, and stroke.…”

Section: Introductionmentioning

confidence: 99%

“…Conditions like hypoxia and/or elevated CO 2 levels caused by hydrocephalus, brain tumors, and respiratory failure can lead to severe cellular and organ damage. 16 The prevalence of diabetes is reaching epidemic levels, giving rise to various complications like microangiopathy, atherosclerosis, coronary heart disease, peripheral vascular disease, peripheral vascular disease, and stroke. Implantable continuous glucose monitoring (CGM) devices 17 enable real-time adjustments to diabetes management by tracking glucose levels in both interstitial fluid and blood, facilitating recognition and treatment of associated symptoms.…”

Section: Introductionmentioning

confidence: 99%

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Recent Development of Implantable Chemical Sensors Utilizing Flexible and Biodegradable Materials for Biomedical Applications

Hu,

Wang,

Liu

et al. 2024

ACS Nano

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Implantable chemical sensors built with flexible and biodegradable materials exhibit immense potential for seamless integration with biological systems by matching the mechanical properties of soft tissues and eliminating device retraction procedures. Compared with conventional hospital-based blood tests, implantable chemical sensors have the capability to achieve real-time monitoring with high accuracy of important biomarkers such as metabolites, neurotransmitters, and proteins, offering valuable insights for clinical applications. These innovative sensors could provide essential information for preventive diagnosis and effective intervention. To date, despite extensive research on flexible and bioresorbable materials for implantable electronics, the development of chemical sensors has faced several challenges related to materials and device design, resulting in only a limited number of successful accomplishments. This review highlights recent advancements in implantable chemical sensors based on flexible and biodegradable materials, encompassing their sensing strategies, materials strategies, and geometric configurations. The following discussions focus on demonstrated detection of various objects including ions, small molecules, and a few examples of macromolecules using flexible and/or bioresorbable implantable chemical sensors. Finally, we will present current challenges and explore potential future directions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent Development of Implantable Chemical Sensors Utilizing Flexible and Biodegradable Materials for Biomedical Applications

Hu,

Wang,

Liu

et al. 2024

ACS Nano

View full text Add to dashboard Cite

show abstract

“…While studies to understand the significance of these networks in maintaining brain health and function are ongoing [9,10], there is limited knowledge regarding glymphatic function in the presence of a brain tumor. In addition to biochemical effects from cancer cells, tumor-induced mechanical forces may damage the brain [11] and severely impact waste clearance in brain tumor patients [12][13][14][15][16][17][18]. However, the mechanisms of this effect have yet to be fully elucidated [2].…”

Section: Introductionmentioning

confidence: 99%

Simulating the Impact of Tumor Mechanical Forces on Glymphatic Networks in the Brain Parenchyma

Siri,

Burchett,

Datta

2024

Preprint

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Background: The brain glymphatic system is currently being explored in the context of many neurological disorders and diseases, including traumatic brain injury, Alzheimer's disease, and ischemic stroke. However, little is known about the impact of brain tumors on glymphatic function. Mechanical forces generated during tumor development and growth may be responsible for compromised glymphatic transport pathways, reducing waste clearance and cerebrospinal fluid (CSF) transport in the brain parenchyma. One such force is solid stress, i.e., growth-induced forces from cell hyperproliferation and excess matrix deposition. Because there are no prior studies assessing the impact of tumor-derived solid stress on glymphatic system structure and performance in the brain parenchyma, this study serves to fill an important gap in the field. Methods: We adapted a previously developed Electrical Analog Model using MATLAB Simulink for glymphatic transport coupled with Finite Element Analysis for tumor mechanical stresses and strains in COMSOL. This allowed simulation of the impact of tumor mechanical force generation on fluid transport within brain parenchymal glymphatic units, which include paravascular spaces, astrocytic networks, interstitial spaces, and capillary basement membranes. We conducted a parametric analysis to compare the contributions of tumor size, tumor proximity, and ratio of glymphatic subunits to the stress and strain experienced by the glymphatic unit and corresponding reduction in flow rate of CSF. Results:. Mechanical stresses intensify with proximity to the tumor and increasing tumor size, highlighting the vulnerability of nearby glymphatic units to tumor-derived forces. Our stress and strain profiles reveal compressive deformation of these surrounding glymphatics and demonstrate that varying the relative contributions of astrocytes vs. interstitial spaces impact the resulting glymphatic structure significantly under tumor mechanical forces. Increased tumor size and proximity caused increased stress and strain across all glymphatic subunits, as does decreased astrocyte composition. Indeed, our model reveals an inverse correlation between extent of astrocyte contribution to the composition of the glymphatic unit and the resulting mechanical stress. This increased mechanical strain across the glymphatic unit decreases the venous efflux rate of CSF, dependent on the degree of strain and the specific glymphatic subunit of interest. For example, a 20% mechanical strain on capillary basement membranes does not significantly decrease venous efflux (2% decrease in flow rates), while the same magnitude of strain on astrocyte networks and interstitial spaces decreases efflux flow rates by 7% and 22%, respectively. Conclusion: Our simulations reveal that solid stress from brain tumors directly reduces glymphatic fluid transport, independently from biochemical effects from cancer cells. Understanding these pathophysiological implications is crucial for developing targeted interventions aimed at restoring effective waste clearance mechanisms in the brain. This study opens potential avenues for future experimental research in brain tumor-related glymphatic dysfunction.

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Fluids and flows in brain cancer and neurological disorders

Jin

Munson

2022

WIREs Mechanisms of Disease

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Interstitial fluid (IF) and cerebrospinal fluid (CSF) are an integral part of the brain, serving to cushion and protect the brain parenchymal cells against damage and aid in their function. The brain IF contains various ions, nutrients, waste products, peptides, hormones, and neurotransmitters. IF moves primarily by pressure-dependent bulk flow through brain parenchyma, draining into the ventricular CSF. The brain ventricles and subarachnoid spaces are filled with CSF which circulates through the perivascular spaces. It also flows into the IF space regulated, in part, by aquaporin channels, removing waste solutes through a process of IF-CSF mixing. During disease development, the composition, flow, and volume of these fluids changes and can lead to brain cell dysfunction. With the improvement of imaging technology and the help of genomic profiling, more information has been and can be obtained from brain fluids; however, the role of CSF and IF in brain cancer and neurobiological disease is still limited. Here we outline recent advances of our knowledge of brain fluid flow in cancer and neurodegenerative disease based on our understanding of its dynamics and composition.

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Fluids and flows in brain cancer and neurological disorders

Cited by 5 publications

References 144 publications

Recent Development of Implantable Chemical Sensors Utilizing Flexible and Biodegradable Materials for Biomedical Applications

Recent Development of Implantable Chemical Sensors Utilizing Flexible and Biodegradable Materials for Biomedical Applications

Simulating the Impact of Tumor Mechanical Forces on Glymphatic Networks in the Brain Parenchyma

Fluids and flows in brain cancer and neurological disorders

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