| Title |
Involvement of Claudin-11 in Disruption of Blood-Brain, -Spinal Cord, and -Arachnoid Barriers in Multiple Sclerosis
|
|---|---|
| Published in |
Molecular Neurobiology, July 2018
|
| DOI | 10.1007/s12035-018-1207-5 |
| Pubmed ID | |
| Authors |
Yasuo Uchida, Tomohito Sumiya, Masanori Tachikawa, Tatsuya Yamakawa, Sho Murata, Yuta Yagi, Kazuki Sato, Alice Stephan, Katsuaki Ito, Sumio Ohtsuki, Pierre-Olivier Couraud, Takashi Suzuki, Tetsuya Terasaki |
| Abstract |
It is important to understand the molecular mechanisms of barrier disruption in the central nervous system (CNS) of patients with multiple sclerosis (MS). The purpose of the present study was to clarify whether claudin-11 is involved in the disruption of two endothelial barriers (blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB)) and two epithelial barriers (blood-arachnoid barrier (BAB) and blood-CSF barrier (BCSFB)) in the CNS in MS. Immunohistochemical analysis revealed that, in both normal human and mouse, claudin-11 is co-localized with claudin-5 in the brain and spinal cord capillaries. The absolute protein expression level of claudin-11 was nearly equal to that of claudin-5 in rat brain capillaries, but was 2.81-fold greater in human brain capillaries. The protein expressions of claudin-11 were significantly downregulated in the brain and spinal cord capillaries of an MS patient and experimental autoimmune encephalomyelitis (EAE) mice. Specific downregulation of claudin-11 with siRNA significantly increased the transfer of membrane-impermeable FITC-dextran across human brain capillary endothelial cell (hCMEC/D3) monolayer. As for the epithelial barrier, claudin-11 protein expression was not decreased in choroid plexus epithelial cells forming the BCSFB in EAE mice, whereas it was decreased in brain and spinal cord meninges that form the BAB. Specific downregulation of claudin-11 with siRNA in a rat choroid plexus epithelial cell (TR-CSFB) monolayer significantly increased the permeability of FITC-dextran. In conclusion, our present findings indicate that claudin-11 expression at the BBB, BSCB, and BAB, but not the BCSFB, is downregulated in multiple sclerosis, impairing the functional integrity of these barriers. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 62 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 19% |
| Student > Ph. D. Student | 11 | 18% |
| Student > Bachelor | 9 | 15% |
| Student > Doctoral Student | 5 | 8% |
| Student > Master | 4 | 6% |
| Other | 7 | 11% |
| Unknown | 14 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 12 | 19% |
| Neuroscience | 11 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 9 | 15% |
| Immunology and Microbiology | 3 | 5% |
| Medicine and Dentistry | 3 | 5% |
| Other | 8 | 13% |
| Unknown | 16 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 July 2018.
All research outputs
#15,539,088
of 23,094,276 outputs
Outputs from Molecular Neurobiology
#2,085
of 3,498 outputs
Outputs of similar age
#208,975
of 327,340 outputs
Outputs of similar age from Molecular Neurobiology
#90
of 152 outputs
Altmetric has tracked 23,094,276 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,498 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 327,340 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 152 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.