Abstract
The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [ 17 O]H 2 O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [ 17 O]H 2 O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 697-703 |
| Number of pages | 7 |
| Journal | NeuroReport |
| Volume | 29 |
| Issue number | 9 |
| DOIs | |
| State | Published - Jan 1 2018 |
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Keywords
- glia limitans externa
- glymphatic flow
- Virchow-Robin space
- Xenopus laevis
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier : [ 17 O]H 2 O JJVCPE MRI study. / Huber, Vincent J.; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid; Nakada, Tsutomu.
In: NeuroReport, Vol. 29, No. 9, 01.01.2018, p. 697-703.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier
T2 - [ 17 O]H 2 O JJVCPE MRI study
AU - Huber, Vincent J.
AU - Igarashi, Hironaka
AU - Ueki, Satoshi
AU - Kwee, Ingrid
AU - Nakada, Tsutomu
PY - 2018/1/1
Y1 - 2018/1/1
N2 - The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [ 17 O]H 2 O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [ 17 O]H 2 O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.
AB - The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [ 17 O]H 2 O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [ 17 O]H 2 O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.
KW - glia limitans externa
KW - glymphatic flow
KW - Virchow-Robin space
KW - Xenopus laevis
UR - http://www.scopus.com/inward/record.url?scp=85047884904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047884904&partnerID=8YFLogxK
U2 - 10.1097/WNR.0000000000000990
DO - 10.1097/WNR.0000000000000990
M3 - Article
C2 - 29481527
AN - SCOPUS:85047884904
VL - 29
SP - 697
EP - 703
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 9
ER -