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.

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 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.

Aquaporin 4 Antibodies in the Cerebrospinal Fluid Are Helpful in Diagnosing Chinese Patients with Neuromyelitis Optica

2012 ◽  
Vol 19 (2) ◽  
pp. 96-102 ◽  
Author(s):  
Youming Long ◽  
Wei Qiu ◽  
Zhengqi Lu ◽  
Jian Bao ◽  
Aimin Wu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neuromyelitis Optica ◽  
Aquaporin 4 ◽  
Chinese Patients

History, Anatomy, Histology, and Embryology of the Ventricles and Physiology of the Cerebrospinal Fluid

2021 ◽  
Author(s):  
Pinar Kuru Bektaşoğlu ◽  
Bora Gürer
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Secretion ◽  
Colorless Liquid ◽  
Brain Ventricles ◽  
Arachnoid Granulations ◽  
Choroid Plexuses ◽  
Subarachnoid Spaces ◽  
The Mean ◽  
The Brain ◽  
Cerebrospinal Fluid Secretion

Cerebrospinal fluid is an essential, clear, and colorless liquid for the homeostasis of the brain and neuronal functioning. It circulates in the brain ventricles, the cranial and spinal subarachnoid spaces. The mean cerebrospinal fluid volume is 150 ml, with 125 ml in subarachnoid spaces and 25 ml in the ventricles. Cerebrospinal fluid is mainly secreted by the choroid plexuses. Cerebrospinal fluid secretion in adults ranges between 400 and 600 ml per day and it is renewed about four or five times a day. Cerebrospinal fluid is mainly reabsorbed from arachnoid granulations. Any disruption in this well-regulated system from overproduction to decreased absorption or obstruction could lead to hydrocephalus.

scholarly journals Comparative Efficacies of Antibiotics in a Rat Model of Meningoencephalitis Due to Listeria monocytogenes

1999 ◽  
Vol 43 (7) ◽  
pp. 1651-1656 ◽  
Author(s):  
Christian Michelet ◽  
Stephen L. Leib ◽  
Daniele Bentue-Ferrer ◽  
Martin G. Täuber
Keyword(s):  
Cerebrospinal Fluid ◽  
Listeria Monocytogenes ◽  
Rat Model ◽  
Antibacterial Effect ◽  
Antibacterial Activities ◽  
The Other ◽  
Active Therapy ◽  
Treatment Regimens ◽  
Infant Rats ◽  
The Brain

ABSTRACT The antibacterial activities of amoxicillin-gentamicin, trovafloxacin, trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of trovafloxacin with TMP-SMX were compared in a model of meningoencephalitis due to Listeria monocytogenes in infant rats. At 22 h after intracisternal infection, the cerebrospinal fluid was cultured to document meningitis, and the treatment was started. Treatment was instituted for 48 h, and efficacy was evaluated 24 h after administration of the last dose. All tested treatment regimens exhibited significant activities in brain, liver, and blood compared to infected rats receiving saline (P < 0.001). In the brain, amoxicillin plus gentamicin was more active than all of the other regimens, and trovafloxacin was more active than TMP-SMX (bacterial titers of 4.1 ± 0.5 log10 CFU/ml for amoxicillin-gentamicin, 5.0 ± 0.4 log10 CFU/ml for trovafloxacin, and 5.8 ± 0.5 log10 CFU/ml for TMP-SMX;P < 0.05). In liver, amoxicillin-gentamicin and trovafloxacin were similarly active (2.8 ± 0.8 and 2.7 ± 0.8 log10 CFU/ml, respectively) but more active than TMP-SMX (4.4 ± 0.6 log10 CFU/ml; P< 0.05). The combination of trovafloxacin with TMP-SMX did not alter the antibacterial effect in the brain, but it did reduce the effect of trovafloxacin in the liver. Amoxicillin-gentamicin was the most active therapy in this study, but the activity of trovafloxacin suggests that further studies with this drug for the treatment ofListeria infections may be warranted.

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 Cerebrospinal fluid aquaporin‐4 antibody levels in neuromyelitis optica attacks

2014 ◽  
Vol 76 (2) ◽  
pp. 305-309 ◽  
Author(s):  
Douglas Kazutoshi Sato ◽  
Dagoberto Callegaro ◽  
Frederico M. Haidar Jorge ◽  
Ichiro Nakashima ◽  
Shuhei Nishiyama ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neuromyelitis Optica ◽  
Aquaporin 4 ◽  
Antibody Levels ◽  
Aquaporin 4 Antibody

scholarly journals Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders.

2020 ◽  
Author(s):  
Leung-Wah Yick ◽  
Chi-Ho Tang ◽  
Oscar Ka-Fai Ma ◽  
Jason Shing-Cheong Kwan ◽  
Koon Ho CHAN
Keyword(s):  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neurotrophic Factor ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Glutamate Excitotoxicity ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Motor Impairments ◽  
Spectrum Disorders

Abstract Background: Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG. Methods: Purified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA. Results: Oral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the spinal cord. Conclusions: Our findings support that glutamate excitotoxicity and neuroinflammation plays important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.

ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease

2021 ◽  
Author(s):  
Mitsuru Shinohara ◽  
Junko Hirokawa ◽  
Akemi Shimodaira ◽  
Yoshitaka Tashiro ◽  
Kaoru Suzuki ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Brain Regions ◽  
Insoluble Fraction ◽  
The Other ◽  
Disease Stage ◽  
Brain Areas ◽  
Postmortem Brains ◽  
Biochemical Level ◽  
The Brain ◽  
Control Samples

Abstract Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak neurofibrillary tangles stage, Aβ accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.

scholarly journals IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel

2005 ◽  
Vol 202 (4) ◽  
pp. 473-477 ◽  
Author(s):  
Vanda A. Lennon ◽  
Thomas J. Kryzer ◽  
Sean J. Pittock ◽  
A.S. Verkman ◽  
Shannon R. Hinson
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Blood Brain Barrier ◽  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Protein Complex ◽  
Demyelinating Disease ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Specific Marker

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.

Sign in / Sign up

Export Citation Format

Share Document