scholarly journals Elucidating the Role of Matrix Porosity and Rigidity in Glioblastoma Type IV Progression

2020 ◽  
Vol 10 (24) ◽  
pp. 9076
Author(s):  
Rui C. Pereira ◽  
Raffaella Santagiuliana ◽  
Luca Ceseracciu ◽  
Daniela P. Boso ◽  
Bernhard A. Schrefler ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Brain Parenchyma ◽  
Collagen Gels ◽  
Computational Framework ◽  
Type Iv ◽  
Quantitative Studies ◽  
Matrix Porosity ◽  
Matrix Heterogeneity ◽  
The Brain

The highly infiltrating nature of glioma cells is the major cause for the poor prognosis of brain malignancies. Motility, proliferation, and gene expression of cells in natural and synthetic gels have been analyzed by several authors, yet quantitative studies elucidating the role of matrix porosity and rigidity in the development of whole malignant masses are missing. Here, an experimental-computational framework is introduced to analyze the behavior of U87-MG cells and spheroids in compact hyaluronic acid gels (HA), replicating the brain parenchyma; and fibrous collagen gels (COL), resembling the organized structures of the brain. Experimentally it was observed that individual U87-MG cells in COL assumed an elongated morphology within a few hours post inclusion (p.i.) and travelled longer distances than in HA. As spheroids, U87-MG cells rapidly dispersed into COL resulting in infiltrating regions as large as tumor cores (≈600 μm, at 8 days p.i.). Conversely, cells in HA originated smaller and denser infiltrating regions (≈300 μm, at 8 days p.i.). Notably, COL tumor core size was only 20% larger than in HA, at longer time points. Computationally, by introducing for the first time the effects of matrix heterogeneity in our numerical simulations, the results confirmed that matrix porosity and its spatial organization are key factors in priming the infiltrating potential of these malignant cells. The experimental-numerical synergy can be used to predict the behavior of neoplastic masses under diverse conditions and the efficacy of combination therapies simultaneously aiming at killing cancer cells and modulating the tumor microenvironment.

scholarly journals PPAR Gamma and Viral Infections of the Brain

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas
Keyword(s):  
Viral Infections ◽  
Ppar Gamma ◽  
Brain Parenchyma ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immunodeficiency Virus ◽  
Health And Disease ◽  
The Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

scholarly journals Role of the glymphatic system in ageing and diabetes mellitus impaired cognitive function

2019 ◽  
Vol 4 (2) ◽  
pp. 90-92 ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Quan Jiang ◽  
Zhenggang Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Cognitive Impairment ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Brain Parenchyma ◽  
Glymphatic System ◽  
Impaired Cognitive Function ◽  
Increased Risk ◽  
The Brain

Diabetes mellitus (DM) is a common metabolic disease in the middle-aged and older population, and is associated with cognitive impairment and an increased risk of developing dementia. The glymphatic system is a recently characterised brain-wide cerebrospinal fluid and interstitial fluid drainage pathway that enables the clearance of interstitial metabolic waste from the brain parenchyma. Emerging data suggest that DM and ageing impair the glymphatic system, leading to accumulation of metabolic wastes including amyloid-β within the brain parenchyma, and consequently provoking cognitive dysfunction. In this review, we concisely discuss recent findings regarding the role of the glymphatic system in DM and ageing associated cognitive impairment.

Definition of the Role of Contemporary Surgical Management in Cisternal and Parenchymatous Cysticercosis Cerebri

Neurosurgery ◽  
1991 ◽  
Vol 28 (2) ◽  
pp. 231-237 ◽  
Author(s):  
William T. Couldwell ◽  
Chi-Shing Zee ◽  
Michael L. J. Apuzzo
Keyword(s):  
Symptomatic Improvement ◽  
Brain Parenchyma ◽  
Cystic Mass ◽  
Increased Intracranial Pressure ◽  
Focal Neurological Deficit ◽  
Definition Of ◽  
Mass Lesions ◽  
The Brain

Abstract With increasing immigration from endemic regions, the incidence of neurocysticercosis in North America is rising. This retrospective study was undertaken to examine the role of surgery in those cases presenting with large cystic parenchymal and cisternal lesions in the current era of anthelminthic agents administered orally. A total of 237 patients presented with newly diagnosed neurocysticercosis to our institution over a recent 5-year period (mean age, 31.2 years). Among those who presented with cystic mass lesions predominantly affecting the brain parenchyma and cisternal spaces. 20 (8.4%; mean age, 40.2 years) with large cystic lesions subsequently underwent surgical intervention, either because of an emergent presentation or because they were refractory to medical management. Clinical presentation included increased intracranial pressure, focal neurological deficit, and seizure. Radiographic imaging (computed tomography and/or magnetic resonance imaging) demonstrated 12 cases with cisternal lesions, 7 with parenchymal lesions, and 1 involving both compartments. Based on imaging guidelines, 30 operative procedures (excluding shunt revisions) were performed (14 craniotomies, 8 cerebrospinal fluid diversions, 7 stereotactic procedures, and 1 burr hole drainage). Fifteen (75%) showed neurological or symptomatic improvement over a median follow-up period of 36.4 months. There were three surgery-related complications and no deaths.

Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells

2007 ◽  
Vol 293 (3) ◽  
pp. C1181-C1185 ◽  
Author(s):  
Sandra B. Ross ◽  
Catherine M. Fuller ◽  
James K. Bubien ◽  
Dale J. Benos
Keyword(s):  
Ion Channel ◽  
Potential Role ◽  
Glioma Cells ◽  
Brain Parenchyma ◽  
Volume Increase ◽  
Cation Conductance ◽  
Normal Human ◽  
Hyperosmolar Solutions ◽  
The Brain

Despite intensive research, brain tumors remain among the most difficult type of malignancies to treat, due largely to their diffusely invasive nature and the associated difficulty of adequate surgical resection. To migrate through the brain parenchyma and to proliferate, glioma cells must be capable of significant changes in shape and volume. We have previously reported that glioma cells express an amiloride- and psalmotoxin-sensitive cation conductance that is not found in normal human astrocytes. In the present study, we investigated the potential role of this ion channel to mediate regulatory volume increase in glioma cells. We found that the ability of the cells to volume regulate subsequent to cell shrinkage by hyperosmolar solutions was abolished by both amiloride and psalmotoxin 1. This toxin is thought to be a specific peptide inhibitor of acid-sensing ion channel (ASIC1), a member of the Deg/ENaC superfamily of cation channels. We have previously shown this toxin to be an effective blocker of the glioma cation conductance. Our data suggest that one potential role for this conductance may be to restore cell volume during the cell's progression thorough the cell cycle and while the tumor cell migrates within the interstices of the brain.

scholarly journals Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake

2021 ◽  
Vol 153 (8) ◽  
Author(s):  
Alex J. Smith ◽  
Gokhan Akdemir ◽  
Meetu Wadhwa ◽  
Dan Song ◽  
Alan S. Verkman
Keyword(s):  
Constant Pressure ◽  
Water Channel ◽  
Solute Concentration ◽  
External Pressure ◽  
Brain Parenchyma ◽  
Interstitial Space ◽  
Brain Surface ◽  
Solute Uptake ◽  
The Brain

Extracellular solutes in the central nervous system are exchanged between the interstitial fluid, the perivascular compartment, and the cerebrospinal fluid (CSF). The “glymphatic” mechanism proposes that the astrocyte water channel aquaporin-4 (AQP4) is a major determinant of solute transport between the CSF and the interstitial space; however, this is controversial in part because of wide variance in experimental data on interstitial uptake of cisternally injected solutes. Here, we investigated the determinants of solute uptake in brain parenchyma following cisternal injection and reexamined the role of AQP4 using a novel constant-pressure method. In mice, increased cisternal injection rate, which modestly increased intracranial pressure, remarkably increased solute dispersion in the subarachnoid space and uptake in the cortical perivascular compartment. To investigate the role of AQP4 in the absence of confounding variations in pressure and CSF solute concentration over time and space, solutes were applied directly onto the brain surface after durotomy under constant external pressure. Pressure elevation increased solute penetration into the perivascular compartment but had little effect on parenchymal solute uptake. Solute penetration and uptake did not differ significantly between wild-type and AQP4 knockout mice. Our results offer an explanation for the variability in cisternal injection studies and indicate AQP4-independent solute transfer from the CSF to the interstitial space in mouse brain.

scholarly journals Topographic connectivity reveals task-dependent retinotopic processing throughout the human brain.

2020 ◽  
Author(s):  
Tomas Knapen
Keyword(s):  
Visual System ◽  
Spatial Organization ◽  
Brain Regions ◽  
Retinotopic Mapping ◽  
Visual Spatial ◽  
Retinotopic Maps ◽  
Sensory Predictions ◽  
Visual Organization ◽  
The Brain

The human visual system is organized as a hierarchy of maps that share the retina's topography. Although retinotopic maps have been identified throughout the brain, how much of the brain is visually organized remains unknown. Here we demonstrate widespread stable visual organization beyond the traditional visual system by analyzing topographic connectivity with primary visual cortex during moviewatching, rest, and retinotopic mapping. Detailed visual-spatial organization derived from retinotopic connectivity is modulated by experimental condition. Specifically, traditionally visual regions alternate with default mode network and hippocampus in preferentially representing the center of the visual field. This visual role of hippocampus would allow it to implement sensory predictions by interfacing between abstract memories and concrete perceptions. These results indicate that pervasive sensory coding facilitates the communication between far-flung brain regions.

scholarly journals The Presence and Potential Role of ALDH1A2 in the Glioblastoma Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2485
Author(s):  
Stephanie Sanders ◽  
Denise M. Herpai ◽  
Analiz Rodriguez ◽  
Yue Huang ◽  
Jeff Chou ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Potential Role ◽  
Therapeutic Agents ◽  
Brain Parenchyma ◽  
Low Grade ◽  
Effective Management ◽  
Diffuse Infiltration ◽  
Protein Levels ◽  
The Brain

Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.

scholarly journals Regulation of amyloid-β dynamics and pathology by the circadian clock

2018 ◽  
Vol 215 (4) ◽  
pp. 1059-1068 ◽  
Author(s):  
Geraldine J. Kress ◽  
Fan Liao ◽  
Julie Dimitry ◽  
Michelle R. Cedeno ◽  
Garret A. FitzGerald ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Amyloid Β ◽  
Amyloid Plaque ◽  
Brain Parenchyma ◽  
Targeted Deletion ◽  
Plaque Deposition ◽  
The Brain ◽  
Core Clock Gene

Nighttime restlessness and daytime drowsiness are common and early symptoms of Alzheimer’s Disease (AD). This symptomology implicates dysfunctional biological timing, yet the role of the circadian system in AD pathogenesis is unknown. To evaluate the role of the circadian clock in amyloid-β (Aβ) dynamics and pathology, we used a mouse model of β-amyloidosis and disrupted circadian clock function either globally or locally in the brain via targeted deletion of the core clock gene Bmal1. Our results demonstrate that loss of central circadian rhythms leads to disruption of daily hippocampal interstitial fluid Aβ oscillations and accelerates amyloid plaque accumulation, whereas loss of peripheral Bmal1 in the brain parenchyma increases expression of Apoe and promotes fibrillar plaque deposition. These results provide evidence that both central circadian rhythms and local clock function influence Aβ dynamics and plaque formation and demonstrate mechanisms by which poor circadian hygiene may directly influence AD pathogenesis.

scholarly journals The Role of Urocortins in Intracerebral Hemorrhage

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 96 ◽  
Author(s):  
Ker Woon Choy ◽  
Andy Po-Yi Tsai ◽  
Peter Bor-Chian Lin ◽  
Meng-Yu Wu ◽  
Chihyi Lee ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Regions ◽  
Brain Parenchyma ◽  
Protective Mechanisms ◽  
Neuroprotective Effects ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
G Protein Coupled ◽  
The Brain

Intracerebral hemorrhage (ICH) causes an accumulation of blood in the brain parenchyma that disrupts the normal neurological function of the brain. Despite extensive clinical trials, no medical or surgical therapy has shown to be effective in managing ICH, resulting in a poor prognosis for the patients. Urocortin (UCN) is a 40-amino-acid endogenous neuropeptide that belongs to the corticotropin-releasing hormone (CRH) family. The effect of UCN is activated by binding to two G-protein coupled receptors, CRH-R1 and CRH-R2, which are expressed in brain neurons and glial cells in various brain regions. Current research has shown that UCN exerts neuroprotective effects in ICH models via anti-inflammatory effects, which generally reduced brain edema and reduced blood-brain barrier disruption. These effects gradually help in the improvement of the neurological outcome, and thus, UCN may be a potential therapeutic target in the treatment of ICH. This review summarizes the data published to date on the role of UCN in ICH and the possible protective mechanisms underlined.

scholarly journals Waste Clearance in the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Jasleen Kaur ◽  
Lara M. Fahmy ◽  
Esmaeil Davoodi-Bojd ◽  
Li Zhang ◽  
Guangliang Ding ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Lymphatic Vessels ◽  
Brain Parenchyma ◽  
Perivascular Spaces ◽  
Future Directions ◽  
Relevant Role ◽  
Healthy Functioning ◽  
The Brain ◽  
Brain Homeostasis

Waste clearance (WC) is an essential process for brain homeostasis, which is required for the proper and healthy functioning of all cerebrovascular and parenchymal brain cells. This review features our current understanding of brain WC, both within and external to the brain parenchyma. We describe the interplay of the blood-brain barrier (BBB), interstitial fluid (ISF), and perivascular spaces within the brain parenchyma for brain WC directly into the blood and/or cerebrospinal fluid (CSF). We also discuss the relevant role of the CSF and its exit routes in mediating WC. Recent discoveries of the glymphatic system and meningeal lymphatic vessels, and their relevance to brain WC are highlighted. Controversies related to brain WC research and potential future directions are presented.

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