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.

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

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 New optical method for analyzing cortical blood flow heterogeneity in small animals: validation of the method

2000 ◽  
Vol 279 (3) ◽  
pp. H1291-H1298 ◽  
Author(s):  
Istvan Schiszler ◽  
Minoru Tomita ◽  
Yasuo Fukuuchi ◽  
Norio Tanahashi ◽  
Koji Inoue
Keyword(s):  
Blood Flow ◽  
Mean Transit Time ◽  
Region Of Interest ◽  
Brain Parenchyma ◽  
Sprague Dawley ◽  
Doppler Flowmetry ◽  
Cranial Window ◽  
Brain Surface ◽  
Fine Glass ◽  
The Brain

In pentobarbital-anesthetized male Sprague-Dawley rats, a small cranial window was trephined, and the cortex was transilluminated with a fine glass fiber inserted into the brain parenchyma. The light intensity at the surface area of 2 × 2 mm was recorded during intracarotid injection of 25 μl of carbon black (CB) solution. The region of interest (ROI) was divided into a 50 × 50 matrix, and the mean transit time of CB transport was calculated in each matrix element. We found rapid transits of CB along the microvasculature, with considerable heterogeneity in the avascular area, and heterogeneous efficiency in autoregulatory capacity in the ROI during hypotension. The method was validated by comparison with laser-Doppler flowmetry. The average mean difference was 0.03 ± 0.05%. Five percent CO2 inhalation increased the flow by 85%, but heterogeneously. We concluded that the technique is exclusively sensitive to indicator transits in a very small area on the brain surface with potential usefulness in detecting regional heterogeneity in blood flow.

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.

scholarly journals Aquaporin-4 Expression during Toxic and Autoimmune Demyelination

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2187
Author(s):  
Sven Olaf Rohr ◽  
Theresa Greiner ◽  
Sarah Joost ◽  
Sandra Amor ◽  
Paul van der Valk ◽  
...  
Keyword(s):  
Immune Cells ◽  
Water Channel ◽  
Staining Intensity ◽  
Brain Parenchyma ◽  
Aquaporin 4 ◽  
Aqp4 Expression ◽  
Humoral Immune ◽  
Autoimmune Demyelination ◽  
Peripheral Immune Cells ◽  
The Brain

The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood–brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several studies have addressed the expression and function of AQP4 during inflammatory demyelination, relatively little is known about its expression during non-autoimmune-mediated myelin damage. In this study, we used the toxin-induced demyelination model cuprizone as well as a combination of metabolic and autoimmune myelin injury (i.e., Cup/EAE) to investigate AQP4 pathology. We show that during toxin-induced demyelination, diffuse AQP4 expression increases, while polarized AQP4 expression at the astrocyte endfeet decreases. The diffuse increased expression of AQP4 was verified in chronic-active multiple sclerosis lesions. Around inflammatory brain lesions, AQP4 expression dramatically decreased, especially at sites where peripheral immune cells penetrate the brain parenchyma. Humoral immune responses appear not to be involved in this process since no anti-AQP4 antibodies were detected in the serum of the experimental mice. We provide strong evidence that the diffuse increase in anti-AQP4 staining intensity is due to a metabolic injury to the brain, whereas the focal, perivascular loss of anti-AQP4 immunoreactivity is mediated by peripheral immune cells.

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 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.

The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface

2012 ◽  
Vol 302 (3) ◽  
pp. F316-F328 ◽  
Author(s):  
Y. Zhou ◽  
S. Holmseth ◽  
R. Hua ◽  
A. C. Lehre ◽  
A. M. Olofsson ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Renal Medulla ◽  
Brain Parenchyma ◽  
Ependymal Cells ◽  
Main Role ◽  
Mrna Levels ◽  
Physiological Importance ◽  
Brain Surface ◽  
Negative Controls ◽  
The Brain

The Na+- and Cl−-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produced a number of BGT1 antibodies, and used these to study BGT1 distribution in mice. BGT1 (protein and mRNA) is predominantly expressed in the liver (sinusoidal hepatocyte plasma membranes) and not in the endothelium. BGT1 is also present in the renal medulla, where it localizes to the basolateral membranes of collecting ducts (particularly at the papilla tip) and the thick ascending limbs of Henle. There is some BGT1 in the leptomeninges, but brain parenchyma, brain blood vessels, ependymal cells, the renal cortex, and the intestine are virtually BGT1 deficient in 1- to 3-mo-old mice. Labeling specificity was assured by processing tissue from BGT1-deficient littermates in parallel as negative controls. Addition of 2.5% sodium chloride to the drinking water for 48 h induced a two- to threefold upregulation of BGT1, tonicity-responsive enhancer binding protein, and sodium- myo-inositol cotransporter 1 (slc5a3) in the renal medulla, but not in the brain and barely in the liver. BGT1-deficient and wild-type mice appeared to tolerate the salt treatment equally well, possibly because betaine is one of several osmolytes. In conclusion, this study suggests that BGT1 plays its main role in the liver, thereby complementing other betaine-transporting carrier proteins (e.g., slc6a20) that are predominantly expressed in the small intestine or kidney rather than the liver.

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