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

2021 ◽  
Vol 22 (18) ◽  
pp. 9745
Author(s):  
José Luis Trillo-Contreras ◽  
Juan José Toledo-Aral ◽  
Javier Villadiego ◽  
Miriam Echevarría
Keyword(s):  
Cognitive Deficits ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Ependymal Cells ◽  
Cerebral Tissue ◽  
Principal Characteristics ◽  
Aqp4 Expression ◽  
Aged Mice ◽  
The Brain ◽  
Ventricular Distensibility

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. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4−/− mice, the impairment in CSF drainage and ventricular distensibility was completely reverted by re-normoxia, indicating that AQP4 has a structural role in the chronification of those alterations. Finally, we show that aged mice subjected to two hypoxic episodes experience permanent ventriculomegaly. These data reveal that repetitive hypoxic events in aged cerebral tissue promote the permanent alterations involved in hydrocephalic pathophysiology, which are dependent on AQP4 expression.

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.

scholarly journals Aquaporin 4 over-expression in metastases to the brain in breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Water Channel ◽  
Breast Tumors ◽  
Aquaporin 4 ◽  
Primary Breast Tumor ◽  
Over Expression ◽  
Patients With Cancer ◽  
Public Datasets ◽  
The Brain

Brain metastases affect 10-15% of women with breast cancer (1). Metastasis is the most significant contributor to death in patients with cancer (2). We assessed what genes make brain metastases most different from the breast tumors from which they arose using public datasets (3, 4). The aquaporin 4 (AQP4) water channel (5) was one of the most differentially expressed genes in brain metastases when comparing the transcriptomes of matched tumor and metastasis samples from the brain and breast from 16 patients (2). Analysis of a separate dataset showed demonstrated the same result (4). In both cases, aquaporin 4 was expressed at significantly higher levels in metastases to the brain than in the primary breast tumor. This is the first report of aquaporin 4 differential over-expression in the brain metastases of patients with breast cancer.

The role of aquaporin-4 in cerebral water transport and edema

2007 ◽  
Vol 22 (5) ◽  
pp. 1-7 ◽  
Author(s):  
Orin Bloch ◽  
Geoffrey T. Manley
Keyword(s):  
Water Transport ◽  
Cerebral Edema ◽  
Vasogenic Edema ◽  
Water Channel ◽  
Brain Parenchyma ◽  
Aquaporin 4 ◽  
Molecular Water ◽  
Altered Expression ◽  
Cellular Water ◽  
The Brain

✓Despite decades of research into the pathogenesis of cerebral edema, nonsurgical therapy for brain swelling has advanced very little after more than half a century. Recent advancements in our understanding of molecular water transport have generated interest in new targets for edema therapy. Aquaporin-4 (AQP4) is the primary cellular water channel in the brain, localized to astrocytic foot processes along the blood–brain barrier and brain–cerebrospinal fluid interface. Multiple studies of transgenic mice with a complete deficiency or altered expression of AQP4 suggest a prominent role for AQP4 in cerebral water transport. In models of cellular (cytotoxic) edema, AQP4 deletion or alteration has been shown to be protective, reducing edema burden and improving overall survival. In contrast, AQP4 deletion in extra-cellular (vasogenic) edema results in decreased edema clearance and greater progression of disease. The data strongly support the conclusion that AQP4 plays a pivotal role in cerebral water transport and is an essential mediator in the formation and resorption of edema fluid from the brain parenchyma. These findings also suggest that drug therapy targeting AQP4 function and expression may dramatically alter our ability to treat cerebral edema.

scholarly journals Aquaporin-4 Expression In The Human Choroid Plexus

2021 ◽  
Author(s):  
Felix Deffner ◽  
Corinna Gleiser ◽  
Ulrich Mattheus ◽  
Andreas Wagner ◽  
Peter H Neckel ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Mrna Level ◽  
Age Groups ◽  
Freeze Fracture ◽  
Aquaporin 4 ◽  
Ependymal Cells ◽  
Aqp4 Expression ◽  
Age Related

Abstract Background: The choroid plexus (CP) consists of specialized ependymal cells and underlying stroma and blood vessels, producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In contrast, ventricle-lining ependymal cells express aquaporin-4 (AQP4) basolaterallly. The initial purpose of this study was to analyze the expression of aquaporins in the ependyma – CP transition zone in the human brain to gain insights in aquaporin regulation. The results prompted us to investigate aquaporin expression in the mouse CP of different age groups. Methods: We analyzed the CP from eight body donors (age 74-91) applying immunofluorescence, qPCR, and freeze-fracture electron microscopy. We used antibodies against AQP1, AQP4, NKCC1, and Na/K-ATPase. In addition, we compared the CP from young (2 months), adult (12 months) and old (30 months) mice by qPCR and immunofluorescence. Results: Unexpectedly, many cells in the human CP were positive not only for AQP1 but also for AQP4, normally restricted to ependymal cells and astrocytes. Expression of AQP1 and AQP4 was found in the CP of all eight body donors. These results were confirmed by qPCR, and by electron microscopy detecting AQP4-specific orthogonal arrays of particles. To find out whether AQP4 expression correlated with relevant transport-related proteins we investigated expression of NKCC1 and Na/K-ATPase. Immunostaining for NKCC1 was similar to AQP1 and revealed no particular pattern related to AQP4. Co-staining of AQP4 and Na/K-ATPase indicated a trend for an inverse correlation of their expression. To test for the possibility of age-related changes causing AQP4 expression in the CP, we analyzed mouse brains from different age groups and found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Conclusions: We provide evidence for AQP4 expression in the human and murine CP related to aging which likely contributes to the water flow through the CP epithelium and CSF production. In two alternative hypotheses, we discuss this as a beneficial compensatory, or a detrimental mechanism influencing the previously observed CSF changes during aging.

scholarly journals Aquaporins in Brain: Distribution, Physiology, and Pathophysiology

2002 ◽  
Vol 22 (4) ◽  
pp. 367-378 ◽  
Author(s):  
Jérôme Badaut ◽  
François Lasbennes ◽  
Pierre J. Magistretti ◽  
Luca Regli
Keyword(s):  
Neuronal Activity ◽  
Focal Cerebral Ischemia ◽  
Water Flux ◽  
Water Channel ◽  
Ependymal Cells ◽  
Edema Formation ◽  
Water Homeostasis ◽  
Rodent Brain ◽  
Central Plasma ◽  
The Brain

Water homeostasis in the brain is of central physiologic and clinical importance. Neuronal activity and ion water homeostasis are inextricably coupled. For example, the clearance of K+ from areas of high neuronal activity is associated with a concomitant water flux. Furthermore, cerebral edema, a final common pathway of numerous neurologic diseases, including stroke, may rapidly become life threatening because of the rigid encasement of the brain. A water channel family, the aquaporins, facilitates water flux through the plasma membrane of many cell types. In rodent brain, several recent studies have demonstrated the presence of different types of aquaporins. Aquaporin 1 (AQP1) was detected on epithelial cells in the choroid plexus whereas AQP4, AQP5 and AQP9 were localized on astrocytes and ependymal cells. In rodent brain, AQP4 is present on astrocytic end-feet in contact with brain vessels, and AQP9 is found on astrocytic processes and cell bodies. In basal physiologic conditions, AQP4 and AQP9 appear to be implicated in brain homeostasis and in central plasma osmolarity regulation. Aquaporin 4 may also play a role in pathophysiologic conditions, as shown by the reduced edema formation observed after water intoxication and focal cerebral ischemia in AQP4-knockout mice. Furthermore, pathophysiologic conditions may modulate AQP4 and AQP9 expression. For example, AQP4 and AQP9 were shown to be upregulated after ischemia or after traumatic injuries. Taken together, these recent reports suggest that water homeostasis in the brain is maintained by regulatory processes that, by control of aquaporin expression and distribution, induce and organize water movements. Facilitation of these movements may contribute to the development of edema formation after acute cerebral insults such as ischemia or traumatic injury.

scholarly journals The Neuroepithelium Disruption Could Generate Autoantibodies against AQP4 and Cause Neuromyelitis Optica and Hydrocephalus

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Leandro Castañeyra-Ruiz ◽  
Ibrahim González-Marrero ◽  
Agustín Castañeyra-Ruiz ◽  
Juan M. González-Toledo ◽  
María Castañeyra-Ruiz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neuromyelitis Optica ◽  
Water Channel ◽  
The Other ◽  
Aquaporin 4 ◽  
Brain Areas ◽  
Brain Ventricles ◽  
Noncommunicating Hydrocephalus ◽  
Subventricular Zones ◽  
The Brain

Neuromyelitis optica is an inflammatory disease characterized by neuritis and myelitis of the optic nerve. Its physiopathology is connected with the aquaporin-4 water channel, since antibodies against aquaporin-4 have been found in the cerebrospinal fluid and blood of neuromyelitis optica patients. The seropositivity for aquaporin-4 antibodies is used for the diagnosis of neuromyelitis optica or neuromyelitis optica spectrum disease. On the other hand, aquaporin-4 is expressed in astrocyte feet in the brain-blood barrier and subventricular zones of the brain ventricles. Aquaporin-4 expression is high in cerebrospinal fluid in hydrocephalus. Furthermore, neuroepithelial denudation precedes noncommunicating hydrocephalus and this neuroepithelial disruption could allow aquaporin-4 to reach anomalous brain areas where it is unrecognized and induce the generation of aquaporin-4 antibodies which could cause the neuromyelitis optica and certain types of hydrocephalus.

scholarly journals Streptococcal Meningitis Reveals the Presence of Residual Streptococci and Down-Regulated Aquaporin 4 in the Brain

2021 ◽  
Author(s):  
Tatsuya Nakayama
Keyword(s):  
Streptococcal Infection ◽  
Neurological Symptoms ◽  
Aquaporin 4 ◽  
Neurological Damage ◽  
Uninfected Mouse ◽  
Aqp4 Expression ◽  
Pathological Analysis ◽  
Streptococcal Meningitis ◽  
The Relationship ◽  
The Brain

Abstract The pathology of streptococcal meningitis is poorly understood, even though streptococcal infection induces meningitis. The aim of this study was to clarify the relationship between streptococcal meningitis and aquaporin 4 (AQP4) in the mouse brain. After Streptococcus suis infection, the streptococcal number was calculated, and AQP4 mRNA expression in the brain was quantified at 2 and 7 days after infection. At 7 days post-infection, mice with neurological symptoms showed significantly higher S. suis levels in the brain than mice without neurological symptoms. AQP4 expression was significantly decreased in mice with neurological symptoms than in mice without neurological symptoms. Image analysis demonstrated that S. suis progressed to invade the white matter. Pathological analysis revealed that infected mouse brains had higher inflammation and neurological damage scores than uninfected mouse brains. Therefore, mice with neurological symptoms caused by streptococcal meningitis had high S. suis levels in the brain and reduced AQP4 expression.

scholarly journals Immunohistochemical localization of aquaporin 4 (AQP4) in the porcine gastrointestinal tract

2015 ◽  
Vol 84 (4) ◽  
pp. 321-326 ◽  
Author(s):  
Marcin Bartłomiej Arciszewski ◽  
Małgorzata Matysek ◽  
Waldemar Sienkiewicz
Keyword(s):  
Gastrointestinal Tract ◽  
Epithelial Cells ◽  
Colonic Mucosa ◽  
Water Channel ◽  
Immunohistochemical Localization ◽  
Aquaporin 4 ◽  
Enteric Neurons ◽  
Aqp4 Expression ◽  
Enteric Ganglia ◽  
Strong Immunoreactivity

The water channel aquaporin-4 (AQP4) is a protein widely expressed on plasma membrane of a variety of epithelial cells. In this study we investigated the expression of AQP4 in the gastrointestinal tract of the pig using immunohistochemical staining. We found no presence of AQP4 in the different regions of the pig stomach. In the porcine small intestine moderate immunoreactivity to AQP4 was detected in enterocytes (along the villi and in the bottom of the crypts), duodenal Brunner’s glands and in enteric ganglia in cells lying in close vicinity to myenteric as well as submucous neurons. In superficial epithelial cells of the colonic mucosa as well as of caecal and colonic glands a very strong immunoreactivity to AQP4 was found. Both in the myenteric and submucous ganglia of the large intestine AQP4-positive cells surrounding enteric neurons were observed. We concluded that AQP4 expression in the porcine gastrointestinal tract showed some species-dependent differences in relation to other species. Based on the presented distribution pattern of AQP4, it is likely that the aquaporin plays a role in mucous (but not acid) secretion and intestinal absorptive processes in the pig.

scholarly journals Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 90 ◽  
Author(s):  
Simone Mader ◽  
Lior Brimberg
Keyword(s):  
Water Channel ◽  
Aquaporin 4 ◽  
Target Antigen ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Inflammatory Autoimmune Disease ◽  
The Brain ◽  
Astrocytic Endfeet

Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD). Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer’s disease (AD). In this review, we will describe the role of AQP4 in the adult and developing brain as well as its implication for disease.

scholarly journals Protective Role of Early Aquaporin 4 Induction against Postischemic Edema Formation

2008 ◽  
Vol 29 (2) ◽  
pp. 423-433 ◽  
Author(s):  
Lorenz Hirt ◽  
Béatrice Ternon ◽  
Melanie Price ◽  
Nabil Mastour ◽  
Jean-François Brunet ◽  
...  
Keyword(s):  
Water Channel ◽  
Protective Role ◽  
Aquaporin 4 ◽  
Late Time ◽  
Protective Mechanisms ◽  
Edema Formation ◽  
Aqp4 Expression ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption

Aquaporin 4 (AQP4) is a water channel involved in water movements across the cell membrane and is spatially organized on the cell surface in orthogonal array particles (OAPs). Its role in edema formation or resolution after stroke onset has been studied mainly at late time points. We have shown recently that its expression is rapidly induced after ischemia coinciding in time with an early swelling of the ischemic hemisphere. There are two isoforms of AQP4: AQP4-M1 and AQP4-M23. The ratio of these isoforms influences the size of the OAPs but the functional impact is not known. The role of the early induction of AQP4 is not yet known. Thrombin preconditioning in mice provides a useful model to study endogenous protective mechanisms. Using this model, we provide evidence for the first time that the early induction of AQP4 may contribute to limit the formation of edema and that the AQP4-M1 isoform is predominantly induced in the ischemic tissue at this time point. Although it prevents edema formation, the early induction of the AQP4 expression does not prevent the blood—brain barrier disruption, suggesting an effect limited to the prevention of edema formation possibly by removing of water from the tissue.

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