Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches.

Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine (HCys) levels, is associated with increased risks of neurovascular diseases such as stroke or hydrocephalus. HHcy promotes oxidative stress, neuroinflammation, and endothelial dysfunction, disrupting the blood-brain barrier and accelerating neurodegeneration. These processes highlight HCys as both a biomarker and a potential therapeutic target in vascular-related neurological disorders.

Absence of Aquaporin-4 (AQP4) Prolongs the Presence of a CD11c+ Microglial Population during Postnatal Corpus Callosum Development.

Aquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect.

Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus.

AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4 mice (KO) due to stenosis of Silvio's aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice.

Special Issue "Aquaporins in Brain Disease".

Water is an abundant and important component of the human brain, the homeostasis of which is rigorously controlled [...

Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy.

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery.

Aquaporin-4 Expression Switches from White to Gray Matter Regions during Postnatal Development of the Central Nervous System.

Aquaporin-4 (AQP4) is the most abundant water channel in the central nervous system and plays a fundamental role in maintaining water homeostasis there. In adult mice, AQP4 is located mainly in ependymal cells, in the endfeet of perivascular astrocytes, and in the glia limitans. Meanwhile, its expression, location, and function throughout postnatal development remain largely unknown.

Cellular Distribution of Brain Aquaporins and Their Contribution to Cerebrospinal Fluid Homeostasis and Hydrocephalus.

Brain aquaporins facilitate the movement of water between the four water compartments: blood, cerebrospinal fluid, interstitial fluid, and intracellular fluid. This work analyzes the expression of the four most abundant aquaporins (AQPs) (AQP1, AQP4, AQP9, and AQP11) in the brains of mice and discuss their contribution to hydrocephalus. We analyzed available data from single-cell RNA sequencing of the central nervous system of mice to describe the expression of aquaporins and compare their distribution with that based on qPCR, western blot, and immunohistochemistry assays.

Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus.

Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH.

Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus.

Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease.

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels.

The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity.

Predictive Value of Serum Antibodies and Point Mutations of AQP4, AQP1 and MOG in A Cohort of Spanish Patients with Neuromyelitis Optica Spectrum Disorders.

The detection of IgG aquaporin-4 antibodies in the serum of patients with Neuromyelitis optica (NMO) has dramatically improved the diagnosis of this disease and its distinction from multiple sclerosis. Recently, a group of patients have been described who have an NMO spectrum disorder (NMOsd) and who are seronegative for AQP4 antibodies but positive for IgG aquaporin-1 (AQP1) or myelin oligodendrocyte glycoprotein (MOG) antibodies. The purpose of this study was to determine whether AQP1 and MOG could be considered new biomarkers of this disease; and if point mutations in the gDNA of , and genes could be associated with the etiology of NMOsd.

Expression patterns of aquaporin 1 in vascular tumours.

Background: Aquaporins (AQPs) are a family of water channels expressed in various body tissues. Beyond osmotic balance, AQPs have recently been confirmed to be involved in processes related to cancer (tumour proliferation, angiogenesis, etc.).

Expression Pattern of Aquaporin 1 and Aquaporin 3 in Melanocytic and Nonmelanocytic Skin Tumors.

Objectives: Study of aquaporin 1 (AQP1) and aquaporin 3 (AQP3) expression to understand its potential role in the pathophysiology of skin cancer.

Methods: Analysis of AQP1 and AQP3 expression by immunohistochemistry of 72 skin biopsy specimens from melanocytic skin tumors, nonmelanocytic tumors, or healthy samples.

Results: AQP1 showed strong labeling in 100% of benign common melanocytic nevi.

AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis.

Aquaporin 1 (AQP1), expressed in epithelial cells of the choroid plexus, and aquaporin 4 (AQP4) present in ependymal cells and glia limitants have been proposed to play a significant role in cerebrospinal fluid (CSF) production and homeostasis. However, the specific contribution of each water channel to these functions remains unknown, being a subject of debate during the last years. Here, we analyzed in detail how AQP1 and AQP4 participate in different aspects of the CSF homeostasis such as the load and drainage of ventricles, and further explored if these proteins play a role in the ventricular compliance.

Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus.

Aquaporin-4, present in ependymal cells, in glia limiting and abundantly in pericapillary astrocyte foot processes, and aquaporin-1, expressed in choroid plexus epithelial cells, play an important role in cerebrospinal fluid production and may be involved in the pathophysiology of age-dependent hydrocephalus. The finding that brain aquaporins expression is regulated by low oxygen tension led us to investigate how hypoxia and elevated levels of cerebral aquaporins may result in an increase in cerebrospinal fluid production that could be associated with a hydrocephalic condition. Here we have explored, in young and aged mice exposed to hypoxia, whether aquaporin-4 and aquaporin-1 participate in the development of age-related hydrocephalus.

Long-term immunosuppression for CNS mouse xenotransplantation: Effects on nigrostriatal neurodegeneration and neuroprotective carotid body cell therapy.

Background: The use of long-term immunosuppressive treatments on neural transplantation has been controversial during the last decades. Although nowadays there is a consensus about the necessity of maintaining a permanent state of immunosuppression to preserve the survival of cerebral grafts, little is known about the effects that chronic immunosuppression produces both on the neurodegenerative process and on transplants function.

Methods: Here, we establish a new immunosuppressive protocol, based on the discontinuous administration of CsA (15 mg/kg; s.

The Expression of AQP1 IS Modified in Lung of Patients With Idiopathic Pulmonary Fibrosis: Addressing a Possible New Target.

Activation of the epithelial-mesenchymal transition process (EMT) by which alveolar cells in human lung tissue undergo differentiation giving rise to a mesenchymal phenotype (fibroblast/miofibroblasts) has been well recognized as a key element in the origin of idiopathic pulmonary fibrosis (IPF). Here we analyzed expression of AQP1 in lung biopsies of patients diagnosed with IPF, and compared it to biopsies derived from patients with diverse lung pneumonies, such as hypersensitivity pneumonitis, sarcoidosis or normal lungs. Immunostaining for AQP1 showed a clear increment of AQP1 localized in the alveolar epithelium in biopsies from IPF patients alone.

Comparative Analysis for the Presence of IgG Anti-Aquaporin-1 in Patients with NMO-Spectrum Disorders.

Detection of IgG anti-Aquaporin-4 (AQP4) in serum of patients with Neuromyelitis optica syndrome disorders (NMOSD) has improved diagnosis of these processes and differentiation from Multiple sclerosis (MS). Recent findings also claim that a subgroup of patients with NMOSD, serum negative for IgG-anti-AQP4, present antibodies anti-AQP1 instead. Explore the presence of IgG-anti-AQP1 using a previously developed cell-based assay (CBA) highly sensitive to IgG-anti-AQP4.

Role of aquaporins in cell proliferation: What else beyond water permeability?

In addition to the extensive data demonstrating the importance of mammalian AQPs for the movement of water and some small solutes across the cell membrane, there is now a growing body of evidence indicating the involvement of these proteins in numerous cellular processes seemingly unrelated, at least some of them in a direct way, to their canonical function of water permeation. Here, we have presented a broad range of evidence demonstrating that these proteins have a role in cell proliferation by various different mechanisms, namely, by allowing fast cell volume regulation during cell division; by affecting progression of cell cycle and helping maintain the balance between proliferation and apoptosis, and by crosstalk with other cell membrane proteins or transcription factors that, in turn, modulate progression of the cell cycle or regulate biosynthesis pathways of cell structural components. In the end, however, after discussing all these data that strongly support a role for AQPs in the cell proliferation process, it remains impossible to conclude that all these other functions attributed to AQPs occur completely independently of their water permeability, and there is a need for new experiments designed specifically to address this interesting issue.

Chronic and progressive Parkinson's disease MPTP model in adult and aged mice.

Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP-induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment.

Overexpression of AQP3 Modifies the Cell Cycle and the Proliferation Rate of Mammalian Cells in Culture.

Abnormal AQP3 overexpression in tumor cells of different origins has been reported and a role for this enhanced AQP3 expression in cell proliferation and tumor processess has been indicated. To further understand the role AQP3 plays in cell proliferation we explore the effect that stable over expression of AQP3 produces over the proliferation rate and cell cycle of mammalian cells. The cell cycle was analyzed by flow cytometry with propidium iodide (PI) and the cell proliferation rate measured through cell counting and BrdU staining.

Aquaporin-1 plays important role in proliferation by affecting cell cycle progression.

Aquaporin-1 (AQP1) has been associated with tumor development. Here, we investigated how AQP1 may affect cell proliferation. The proliferative rate of adult carotid body (CB) cells, known to proliferate under chronic hypoxia, was analyzed in wild-type (AQP1(+/+) ) and knock out (AQP1(-/-) ) mice, maintained in normoxia or exposed to hypoxia while BrdU was administered.

An immunoassay that distinguishes real neuromyelitis optica signals from a labeling detected in patients receiving natalizumab.

Background: Cell-based assays for neuromyelitis optica (NMO) diagnosis are the most sensitive and specific methods to detect anti-aquaporin 4 (AQP4) antibodies in serum, but some improvements in their quantitative and specificity capacities would be desirable. Thus the aim of the present work was to develop a sensitive quantitative method for detection of anti-AQP4 antibodies that allows clear diagnosis of NMO and distinction of false labeling produced by natalizumab treatment.

Methods: Sera from 167 individuals, patients diagnosed with NMO (16), multiple sclerosis (85), optic neuritis (24), idiopathic myelitis (21), or other neurological disorders (13) and healthy controls (8), were used as the primary antibody in an immunofluorescence assay on HEK cells transfected with the M23 isoform of human AQP4 fused with enhanced green fluorescent protein.

Expression of aquaporins in bronchial tissue and lung parenchyma of patients with chronic obstructive pulmonary disease.

Background: Aquaporins AQP1 and AQP5 are highly expressed in the lung. Recent studies have shown that the expression of these proteins may be mechanistically involved in the airway inflammation and in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma of patients with COPD and COPD-resistant smokers.