scholarly journals Novel Molecular Biomarkers at the Blood-Brain Barrier in ALS

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Danijela Bataveljic ◽  
Milena Milosevic ◽  
Lidija Radenovic ◽  
Pavle Andjus
Keyword(s):  
Membrane Proteins ◽  
Potassium Channel ◽  
Blood Brain Barrier ◽  
Disease Onset ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Inwardly Rectifying Potassium Channel ◽  
Blood Brain ◽  
Inwardly Rectifying

Recently neuroinflammation has gained a particular focus as a key mechanism of ALS. Several studiesin vivoas well asin vitrohave nominated immunoglobulin G (IgG) isolated from ALS patients as an active contributor to disease onset and progression. We have shown that ALS IgG affects astroglial Ca2+excitability and induces downstream activation of phosphatidylinositol 3-kinase. These studies were hampered by a lack of knowledge of the pathway of entry of immune factors in the CNS. Our MRI data revealed the blood-brain barrier BBB leakage and T cell infiltration into brain parenchyma in ALS G93A rats. Since astrocyte ensheathes blood vessel wall contributing to BBB stability and plays an important role in ALS pathogenesis, we have studied astrocytic membrane proteins water channel aquaporin-4 and the inwardly rectifying potassium channel. In this review, we will summarize data related to BBB disruption with particular emphasis on impaired function of astrocytes in ALS. We will discuss implication of membrane proteins expressed on astrocytic endfeet, aquaporin-4, and inwardly rectifying potassium channel in the pathology of ALS. In addition to ALS-specific IgGs, these membrane proteins are proposed as novel biomarkers of the disease.

Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood–brain barrier disturbance but not with patient survival

2007 ◽  
Vol 85 (6) ◽  
pp. 1336-1346 ◽  
Author(s):  
Arne Warth ◽  
Perikles Simon ◽  
David Capper ◽  
Benjamin Goeppert ◽  
Ghazaleh Tabatabai ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Blood Brain Barrier ◽  
Patient Survival ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Human Gliomas ◽  
Blood Brain

scholarly journals Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218415 ◽  
Author(s):  
Yifan Zhang ◽  
Kui Xu ◽  
Yuchi Liu ◽  
Bernadette O. Erokwu ◽  
Pan Zhao ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Knockout Mice ◽  
Water Exchange ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Cerebrospinal fluid aquaporin‐4‐immunoglobulin G disrupts blood brain barrier

2015 ◽  
Vol 2 (8) ◽  
pp. 857-863 ◽  
Author(s):  
Nasrin Asgari ◽  
Carsten Tue Berg ◽  
Marlene Thorsen Mørch ◽  
Reza Khorooshi ◽  
Trevor Owens
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Immunoglobulin G ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Blood Brain

Neurothelin: molecular characteristics and developmental regulation in the chick CNS

Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 129-140
Author(s):  
B. Schlosshauer
Keyword(s):  
Endothelial Cells ◽  
Membrane Proteins ◽  
Molecular Mass ◽  
Blood Brain Barrier ◽  
Adult Brain ◽  
Brain Barrier ◽  
Relative Molecular Mass ◽  
Brain Neurons ◽  
Blood Brain

Neurothelin has recently been identified as a cell surface protein specific for chick endothelial cells forming the blood-brain barrier. Neurons of the adult brain are essentially devoid of neurothelin. In contrast, neurons of the chick retina, which lack blood vessels and accessory astrocytes, express neurothelin. Here we demonstrate that during chick brain development initially neurothelin is expressed probably in all neuroblasts. With proceeding cytodifferentiation, such as vascularization and gliogenesis, brain neurons become neurothelin negative. Coincidentally the endothelial cells forming the blood-brain barrier start to synthesize neurothelin. In contrast to brain neurons, in retina neurons, neurothelin expression increases by one order of magnitude during the course of histogenesis. Coculturing of chick retinal cells with purified rat astrocytes in vitro results in reduction of neural neurothelin expression as quantified by ELISA. Conversely, disruption of the glia-neuron interactions by culturing brain neurons as individualized cells in vitro leads to a reexpression of neurothelin. This is consistent with the hypothesis that astrocytes inhibit neurothelin expression in neurons. Biochemical characterization classifies neurothelin as an integral membrane protein. Temperature-induced-detergent phase separation, phospholipase C digestion and sodium carbonate treatment were employed to distinguish between integral membrane proteins, lipid-anchored proteins and peripheral membrane proteins. Two-dimensional gel electrophoresis reveals an isoelectric point of about 6.4 for neurothelin. Polysaccharide analysis by glycosidase digestion and lectin binding indicates that neurothelin is highly glycosylated. The relative molecular mass of glycosylated neurothelin is 41 × 10(3), whereas the peptide backbone is only 25 × 10(3). The very strict spatiotemporal regulation of neurothelin expression in the central nervous system suggests that neurothelin fulfils possibly a crucial function such as transport of low relative molecular mass components that are essential for neuronal metabolism. The proposed biological activity of neurothelin might be specifically affected by some of its distinct biochemical features.

Apelin-13 Protects against Ischemic Blood-Brain Barrier Damage through the Effects of Aquaporin-4

2017 ◽  
Vol 44 (1-2) ◽  
pp. 10-25 ◽  
Author(s):  
Heling Chu ◽  
Xiaobo Yang ◽  
Chuyi Huang ◽  
Zidan Gao ◽  
Yuping Tang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Neurological Function ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Cell Swelling ◽  
Protective Effects ◽  
Aqp4 Expression ◽  
Blood Brain

Background: Apelin-13 has been found to have protective effects on many neurological diseases, including cerebral ischemia. However, whether Apelin-13 acts on blood-brain barrier (BBB) disruption following cerebral ischemia is largely unknown. Aquaporin-4 (AQP4) has a close link with BBB due to the high concentration in astrocyte foot processes and regulation of astrocytes function. Here, we aimed to test Apelin-13′s effects on ischemic BBB injury and examine whether the effects were dependent on AQP4. Methods: We detected the expression of AQP4 induced by Apelin-13 injection at 1, 3, and 7 days after middle cerebral artery occlusion. Meanwhile, we examined the effects of Apelin-13 on neurological function, infarct volume, and BBB disruption owing to cerebral ischemia in wild type mice, and tested whether such effects were AQP4 dependent by using AQP4 knock-out mice. Furthermore, we assessed the possible signal transduction pathways activated by Apelin-13 to regulate AQP4 expression via astrocyte cultures. Results: It was found that Apelin-13 highly increased AQP4 expression as well as reduced neurological scores and infarct volume. Importantly, Apelin-13 played a role of BBB protection in both types of mice by reducing BBB permeability, increased vascular endothelial growth factor, upregulated endothelial nitric oxide synthase, and downregulated inducible NOS. In morphology, we demonstrated Apelin-13 suppressed tight junction opening and endothelial cell swelling via electron microscopy detection. Meanwhile, Apelin-13 also alleviated apoptosis of astrocytes and promoted angiogenesis. Interestingly, effects of AQP4 on neurological function and infarct volume varied with time course, while AQP4 elicited protective effects on BBB at all time points. Statistical analysis of 2-way analysis of variance with replication indicated that AQP4 was required for these effects. In addition, Apelin-13 upregulated phosphorylation of extracellular signal-regulated kinase (ERK) and Akt as well as AQP4 protein in cultured astrocytes. The latter was inhibited by ERK and phosphatidylinositol 3′-kinase (PI3K) inhibitors. Conclusion: Our data suggest that Apelin-13 protects BBB from disruption after cerebral ischemia both morphologically and functionally, which is highly associated with the increased levels of AQP4, possibly through the activation of ERK and PI3K/Akt pathways. This study provides double targets to protection of ischemic BBB damage, which can present new insights to drugs development.

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