Alpha syntrophin deletion removes the perivascular but not the endothelial pool of aquaporin‐4 at the blood‐brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia
The formation of brain edema, commonly occurring as a potentially lethal complication of acute hyponatremia, is delayed following knockout of the water channel aquaporin‐4 (AQP4). Here we show by high‐resolution immunogold analysis of the blood–brain‐barrier that AQP4 is expressed in brain endotheli...
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| Veröffentlicht in: | The FASEB journal 2004-03, Vol.18 (3), p.542-544 |
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| creator | Amiry‐Moghaddam, Mahmood Xue, Rong Haug, Finn‐Mogens Neely, John D. Bhardwaj, Anish Agre, Peter Adams, Marvin E. Froehner, Stanley C. Mori, Susumu Ottersen, Ole P. |
| description | The formation of brain edema, commonly occurring as a potentially lethal complication of acute hyponatremia, is delayed following knockout of the water channel aquaporin‐4 (AQP4). Here we show by high‐resolution immunogold analysis of the blood–brain‐barrier that AQP4 is expressed in brain endothelial cells as well as in the perivascular membranes of astrocyte endfeet. A selective removal of perivascular AQP4 by α‐syntrophin deletion delays the buildup of brain edema (assessed by Diffusion‐weighted MRI) following water intoxication, despite the presence of a normal complement of endothelial AQP4. This indicates that the perivascular membrane domain, which is peripheral to the endothelial blood–brain barrier, may control the rate of osmotically driven water entry. This study is also the first to demonstrate that the time course of edema development differs among brain regions, probably reflecting differences in aquaporin‐4 distribution. The resolution of the molecular basis and subcellular site of osmotically driven brain water uptake should help design new therapies for acute brain edema. |
| doi_str_mv | 10.1096/fj.03-0869fje |
| format | Article |
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The resolution of the molecular basis and subcellular site of osmotically driven brain water uptake should help design new therapies for acute brain edema.</description><subject>Animals</subject><subject>AQP4</subject><subject>Aquaporin 4</subject><subject>Aquaporins - deficiency</subject><subject>Aquaporins - physiology</subject><subject>Astrocytes - metabolism</subject><subject>Blood-Brain Barrier - physiology</subject><subject>blood‐brain‐barrier</subject><subject>Brain edema</subject><subject>Brain Edema - etiology</subject><subject>Brain Edema - metabolism</subject><subject>Brain Edema - physiopathology</subject><subject>Calcium-Binding Proteins</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Polarity</subject><subject>Cell Surface Extensions - metabolism</subject><subject>Cerebellum - metabolism</subject><subject>Corpus Striatum - metabolism</subject><subject>endothelia</subject><subject>Homeostasis</subject><subject>Hyponatremia - complications</subject><subject>Membrane Proteins - deficiency</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Muscle Proteins - deficiency</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - physiology</subject><subject>Neocortex - metabolism</subject><subject>Organ Specificity</subject><subject>Syntrophin</subject><subject>Water - metabolism</subject><subject>water channel</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EosvCkSvyiVuKHSdxzK1Uu0BViQNwjsbJWJuVE6d2spAbj8DT9QH6JDjNStzg5PHM5_8f6yfkNWeXnKninTleMpGwslDmiE_IhueCJUVZsKdkw0qVJkUhygvyIoQjY4wzXjwnFzyTIov9Dbm_ssMBaJj70bvh0Pa0QYtj63rqsXMnDHQ8IB3QtycI9WTBUz2NtHfj4wD7xsXTtmDp4JylzlC4m2Bwvu0ffv3OKKygts41saE9RBMN3rfoKfTNYgjzatPgCa0bOuzHRWhlscEOaCwg1j-XTZZ59OtcfPpoWE8j0sM8uB7GuHYLL8kzAzbgq_O5Jd_3u2_Xn5LbLx8_X1_dJrWQfJeYNE0h03VTMKakkjUg1CBMaXSuVWnyxsgSJGqhUm6UFkwWeYOqVCbXeanFlrxddQfv7iYMY9W1oUZroUc3hUpyyWTG1X9BLjkveAxvS5IVrL0LwaOphvhh8HPFWbUkXpljxUR1Tjzyb87Ck-6w-UufI47A-xX40Vqc_61W7b9-SPc3TCz3_c1O_AF7ucHy</recordid><startdate>200403</startdate><enddate>200403</enddate><creator>Amiry‐Moghaddam, Mahmood</creator><creator>Xue, Rong</creator><creator>Haug, Finn‐Mogens</creator><creator>Neely, John D.</creator><creator>Bhardwaj, Anish</creator><creator>Agre, Peter</creator><creator>Adams, Marvin E.</creator><creator>Froehner, Stanley C.</creator><creator>Mori, Susumu</creator><creator>Ottersen, Ole P.</creator><general>Federation of American Societies for Experimental Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>200403</creationdate><title>Alpha syntrophin deletion removes the perivascular but not the endothelial pool of aquaporin‐4 at the blood‐brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia</title><author>Amiry‐Moghaddam, Mahmood ; Xue, Rong ; Haug, Finn‐Mogens ; Neely, John D. ; Bhardwaj, Anish ; Agre, Peter ; Adams, Marvin E. ; Froehner, Stanley C. ; Mori, Susumu ; Ottersen, Ole P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371E-f222a4bcd6009797caeaca3f8fb5b98f5df78a7eb3921f9b30765de989f5b58b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>AQP4</topic><topic>Aquaporin 4</topic><topic>Aquaporins - deficiency</topic><topic>Aquaporins - physiology</topic><topic>Astrocytes - metabolism</topic><topic>Blood-Brain Barrier - physiology</topic><topic>blood‐brain‐barrier</topic><topic>Brain edema</topic><topic>Brain Edema - etiology</topic><topic>Brain Edema - metabolism</topic><topic>Brain Edema - physiopathology</topic><topic>Calcium-Binding Proteins</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Polarity</topic><topic>Cell Surface Extensions - metabolism</topic><topic>Cerebellum - metabolism</topic><topic>Corpus Striatum - metabolism</topic><topic>endothelia</topic><topic>Homeostasis</topic><topic>Hyponatremia - complications</topic><topic>Membrane Proteins - deficiency</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Muscle Proteins - deficiency</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle Proteins - physiology</topic><topic>Neocortex - metabolism</topic><topic>Organ Specificity</topic><topic>Syntrophin</topic><topic>Water - metabolism</topic><topic>water channel</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Amiry‐Moghaddam, Mahmood</creatorcontrib><creatorcontrib>Xue, Rong</creatorcontrib><creatorcontrib>Haug, Finn‐Mogens</creatorcontrib><creatorcontrib>Neely, John D.</creatorcontrib><creatorcontrib>Bhardwaj, Anish</creatorcontrib><creatorcontrib>Agre, Peter</creatorcontrib><creatorcontrib>Adams, Marvin E.</creatorcontrib><creatorcontrib>Froehner, Stanley C.</creatorcontrib><creatorcontrib>Mori, Susumu</creatorcontrib><creatorcontrib>Ottersen, Ole P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Amiry‐Moghaddam, Mahmood</au><au>Xue, Rong</au><au>Haug, Finn‐Mogens</au><au>Neely, John D.</au><au>Bhardwaj, Anish</au><au>Agre, Peter</au><au>Adams, Marvin E.</au><au>Froehner, Stanley C.</au><au>Mori, Susumu</au><au>Ottersen, Ole P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha syntrophin deletion removes the perivascular but not the endothelial pool of aquaporin‐4 at the blood‐brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2004-03</date><risdate>2004</risdate><volume>18</volume><issue>3</issue><spage>542</spage><epage>544</epage><pages>542-544</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>The formation of brain edema, commonly occurring as a potentially lethal complication of acute hyponatremia, is delayed following knockout of the water channel aquaporin‐4 (AQP4). Here we show by high‐resolution immunogold analysis of the blood–brain‐barrier that AQP4 is expressed in brain endothelial cells as well as in the perivascular membranes of astrocyte endfeet. A selective removal of perivascular AQP4 by α‐syntrophin deletion delays the buildup of brain edema (assessed by Diffusion‐weighted MRI) following water intoxication, despite the presence of a normal complement of endothelial AQP4. This indicates that the perivascular membrane domain, which is peripheral to the endothelial blood–brain barrier, may control the rate of osmotically driven water entry. This study is also the first to demonstrate that the time course of edema development differs among brain regions, probably reflecting differences in aquaporin‐4 distribution. The resolution of the molecular basis and subcellular site of osmotically driven brain water uptake should help design new therapies for acute brain edema.</abstract><cop>United States</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>14734638</pmid><doi>10.1096/fj.03-0869fje</doi><tpages>17</tpages></addata></record> |
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| subjects | Animals AQP4 Aquaporin 4 Aquaporins - deficiency Aquaporins - physiology Astrocytes - metabolism Blood-Brain Barrier - physiology blood‐brain‐barrier Brain edema Brain Edema - etiology Brain Edema - metabolism Brain Edema - physiopathology Calcium-Binding Proteins Cell Membrane - metabolism Cell Polarity Cell Surface Extensions - metabolism Cerebellum - metabolism Corpus Striatum - metabolism endothelia Homeostasis Hyponatremia - complications Membrane Proteins - deficiency Membrane Proteins - genetics Membrane Proteins - physiology Mice Mice, Knockout Muscle Proteins - deficiency Muscle Proteins - genetics Muscle Proteins - physiology Neocortex - metabolism Organ Specificity Syntrophin Water - metabolism water channel |
| title | Alpha syntrophin deletion removes the perivascular but not the endothelial pool of aquaporin‐4 at the blood‐brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia |
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