Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice.
Aquaporin-4 (AQP4) plays an important role in regulating water exchange across the blood-brain barrier (BBB) and brain-cerebrospinal fluid interface. Studies on AQP-4 knockout mice (AQP4-KO) have reported considerable protection from brain edema induced by acute water intoxication and ischemic strok...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0218415 |
| _version_ | 1818843649410072576 |
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| author | Yifan Zhang Kui Xu Yuchi Liu Bernadette O Erokwu Pan Zhao Chris A Flask Ciro Ramos-Estebanez George W Farr Joseph C LaManna Walter F Boron Xin Yu |
| author_facet | Yifan Zhang Kui Xu Yuchi Liu Bernadette O Erokwu Pan Zhao Chris A Flask Ciro Ramos-Estebanez George W Farr Joseph C LaManna Walter F Boron Xin Yu |
| author_sort | Yifan Zhang |
| collection | DOAJ |
| description | Aquaporin-4 (AQP4) plays an important role in regulating water exchange across the blood-brain barrier (BBB) and brain-cerebrospinal fluid interface. Studies on AQP-4 knockout mice (AQP4-KO) have reported considerable protection from brain edema induced by acute water intoxication and ischemic stroke, identifying AQP4 as a potential target for therapeutic interventions. However, the long-term effects of chronic AQP4 suppression are yet to be elucidated. In the current study, we evaluated the physiological and structural changes in adult AQP4-KO mice using magnetic resonance imaging (MRI) and immunohistochemical analysis. Water exchange across BBB was assessed by tracking an intravenous bolus injection of oxygen-17 (17O) water (H217O) using 17O-MRI. Cerebral blood flow (CBF) was quantified using arterial spin-labeling (ASL) MRI. Capillary density was determined by immunohistochemical staining for glucose transporter-1 (GLUT1). Compared to wildtype control mice, AQP4-KO mice showed a significant reduction in peak and steady-state H217O uptake despite unaltered CBF. Interestingly, a 22% increase in cortical capillary density was observed in AQP4-KO mice. These results suggest that increased cerebral vascularization may be an adaptive response to chronic reduction in water exchange across BBB in AQP4-KO mice. |
| first_indexed | 2024-12-19T05:01:13Z |
| format | Article |
| id | doaj.art-affea4c584254db5b83283ed24ecdffe |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T05:01:13Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-affea4c584254db5b83283ed24ecdffe2022-12-21T20:35:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01146e021841510.1371/journal.pone.0218415Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice.Yifan ZhangKui XuYuchi LiuBernadette O ErokwuPan ZhaoChris A FlaskCiro Ramos-EstebanezGeorge W FarrJoseph C LaMannaWalter F BoronXin YuAquaporin-4 (AQP4) plays an important role in regulating water exchange across the blood-brain barrier (BBB) and brain-cerebrospinal fluid interface. Studies on AQP-4 knockout mice (AQP4-KO) have reported considerable protection from brain edema induced by acute water intoxication and ischemic stroke, identifying AQP4 as a potential target for therapeutic interventions. However, the long-term effects of chronic AQP4 suppression are yet to be elucidated. In the current study, we evaluated the physiological and structural changes in adult AQP4-KO mice using magnetic resonance imaging (MRI) and immunohistochemical analysis. Water exchange across BBB was assessed by tracking an intravenous bolus injection of oxygen-17 (17O) water (H217O) using 17O-MRI. Cerebral blood flow (CBF) was quantified using arterial spin-labeling (ASL) MRI. Capillary density was determined by immunohistochemical staining for glucose transporter-1 (GLUT1). Compared to wildtype control mice, AQP4-KO mice showed a significant reduction in peak and steady-state H217O uptake despite unaltered CBF. Interestingly, a 22% increase in cortical capillary density was observed in AQP4-KO mice. These results suggest that increased cerebral vascularization may be an adaptive response to chronic reduction in water exchange across BBB in AQP4-KO mice.https://doi.org/10.1371/journal.pone.0218415 |
| spellingShingle | Yifan Zhang Kui Xu Yuchi Liu Bernadette O Erokwu Pan Zhao Chris A Flask Ciro Ramos-Estebanez George W Farr Joseph C LaManna Walter F Boron Xin Yu Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice. PLoS ONE |
| title | Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice. |
| title_full | Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice. |
| title_fullStr | Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice. |
| title_full_unstemmed | Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice. |
| title_short | Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice. |
| title_sort | increased cerebral vascularization and decreased water exchange across the blood brain barrier in aquaporin 4 knockout mice |
| url | https://doi.org/10.1371/journal.pone.0218415 |
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