Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet
Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is pro...
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| Veröffentlicht in: | Journal of Cerebral Blood Flow & Metabolism 2005-08, Vol.25 (8), p.998-1011 |
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| creator | Lo, Amy CY Chen, Ann YS Hung, Victor KL Yaw, Lai Ping Fung, Maggie KL Ho, Maggie CY Tsang, Margaret CS Chung, Stephen SM Chung, Sookja K |
| description | Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ETA antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury. |
| doi_str_mv | 10.1038/sj.jcbfm.9600108 |
| format | Article |
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Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ETA antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1038/sj.jcbfm.9600108</identifier><identifier>PMID: 15815585</identifier><identifier>CODEN: JCBMDN</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Aquaporin 4 ; Aquaporins - biosynthesis ; Astrocytes - metabolism ; Astrocytes - ultrastructure ; Biological and medical sciences ; Blood Pressure - physiology ; Blood-Brain Barrier - physiology ; Blotting, Western ; Brain - pathology ; Brain Edema - etiology ; Brain Edema - metabolism ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; Coloring Agents ; Endothelin A Receptor Antagonists ; Endothelin B Receptor Antagonists ; Endothelin-1 - biosynthesis ; Enzyme-Linked Immunosorbent Assay ; Evans Blue ; Fundamental and applied biological sciences. Psychology ; Glial Fibrillary Acidic Protein - genetics ; Glial Fibrillary Acidic Protein - metabolism ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; In Situ Hybridization ; Infarction, Middle Cerebral Artery - complications ; Infarction, Middle Cerebral Artery - metabolism ; Infarction, Middle Cerebral Artery - pathology ; Medical sciences ; Mice ; Mice, Transgenic ; Nervous system (semeiology, syndromes) ; Nervous System Diseases - etiology ; Neurology ; Reperfusion Injury - metabolism ; Reperfusion Injury - pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular diseases and vascular malformations of the nervous system ; Vertebrates: nervous system and sense organs ; Water - metabolism</subject><ispartof>Journal of Cerebral Blood Flow & Metabolism, 2005-08, Vol.25 (8), p.998-1011</ispartof><rights>2005 ISCBFM</rights><rights>2005 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Aug 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-f5cd1776c19efabd9c7708bc68d28a5b00ff1b2031da7f005d28b1422b9f763f3</citedby><cites>FETCH-LOGICAL-c500t-f5cd1776c19efabd9c7708bc68d28a5b00ff1b2031da7f005d28b1422b9f763f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1038/sj.jcbfm.9600108$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1038/sj.jcbfm.9600108$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>313,314,776,780,788,21798,27899,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17047751$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15815585$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lo, Amy CY</creatorcontrib><creatorcontrib>Chen, Ann YS</creatorcontrib><creatorcontrib>Hung, Victor KL</creatorcontrib><creatorcontrib>Yaw, Lai Ping</creatorcontrib><creatorcontrib>Fung, Maggie KL</creatorcontrib><creatorcontrib>Ho, Maggie CY</creatorcontrib><creatorcontrib>Tsang, Margaret CS</creatorcontrib><creatorcontrib>Chung, Stephen SM</creatorcontrib><creatorcontrib>Chung, Sookja K</creatorcontrib><title>Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet</title><title>Journal of Cerebral Blood Flow & Metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ETA antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury.</description><subject>Animals</subject><subject>Aquaporin 4</subject><subject>Aquaporins - biosynthesis</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - ultrastructure</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - physiology</subject><subject>Blood-Brain Barrier - physiology</subject><subject>Blotting, Western</subject><subject>Brain - pathology</subject><subject>Brain Edema - etiology</subject><subject>Brain Edema - metabolism</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>Coloring Agents</subject><subject>Endothelin A Receptor Antagonists</subject><subject>Endothelin B Receptor Antagonists</subject><subject>Endothelin-1 - biosynthesis</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Evans Blue</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glial Fibrillary Acidic Protein - genetics</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>In Situ Hybridization</subject><subject>Infarction, Middle Cerebral Artery - complications</subject><subject>Infarction, Middle Cerebral Artery - metabolism</subject><subject>Infarction, Middle Cerebral Artery - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Nervous System Diseases - etiology</subject><subject>Neurology</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - pathology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>Water - metabolism</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUuL2zAUhUVp6aTT7rsqotDunLmyI0teekLSFjJk09LuzLUerY0fGckamn80P7PKxBAY6EYXXb5z7oFDyHsGSwaZvPHtslW17ZdFDsBAviALxnmRCGD5S7KAVLAkF_LXFXnjfQsAMuP8NbliXEZO8gV53Ax6nP6YrhkSRvcPxpm_B2e8b8aB7gxqT6eRboOLjKM_cYpvqVToQ4fTicFB01uHzUA32vRI0Z6Qu0brztB1tKsddrR0cXuke6W68GT90CAt7wMeRhelK7q5XI3_0k9uVMepUTTmS7bGTG_JK4udN-_meU1-bDff11-T3f7Lt3W5SxQHmBLLlWZC5IoVxmKtCyUEyFrlUqcSeQ1gLatTyJhGYQF4XNdslaZ1YUWe2eyafD77Htx4H4yfqr7xynQdDmYMvsoliFRmMoIfn4HtGNwQs1UpK_gKUikiBGdIudF7Z2x1cE2P7lgxqE4VVr6tniqs5gqj5MPsG-re6Itg7iwCn2YAvcLOOhxU4y-cgJUQnEUuOXMef5tLuP8e_gdXvrbR</recordid><startdate>20050801</startdate><enddate>20050801</enddate><creator>Lo, Amy CY</creator><creator>Chen, Ann YS</creator><creator>Hung, Victor KL</creator><creator>Yaw, Lai Ping</creator><creator>Fung, Maggie KL</creator><creator>Ho, Maggie CY</creator><creator>Tsang, Margaret CS</creator><creator>Chung, Stephen SM</creator><creator>Chung, Sookja K</creator><general>SAGE Publications</general><general>Lippincott Williams & Wilkins</general><general>Sage Publications Ltd</general><scope>IQODW</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20050801</creationdate><title>Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet</title><author>Lo, Amy CY ; Chen, Ann YS ; Hung, Victor KL ; Yaw, Lai Ping ; Fung, Maggie KL ; Ho, Maggie CY ; Tsang, Margaret CS ; Chung, Stephen SM ; Chung, Sookja K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-f5cd1776c19efabd9c7708bc68d28a5b00ff1b2031da7f005d28b1422b9f763f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Aquaporin 4</topic><topic>Aquaporins - biosynthesis</topic><topic>Astrocytes - metabolism</topic><topic>Astrocytes - ultrastructure</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - physiology</topic><topic>Blood-Brain Barrier - physiology</topic><topic>Blotting, Western</topic><topic>Brain - pathology</topic><topic>Brain Edema - etiology</topic><topic>Brain Edema - metabolism</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>Coloring Agents</topic><topic>Endothelin A Receptor Antagonists</topic><topic>Endothelin B Receptor Antagonists</topic><topic>Endothelin-1 - biosynthesis</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Evans Blue</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glial Fibrillary Acidic Protein - genetics</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>In Situ Hybridization</topic><topic>Infarction, Middle Cerebral Artery - complications</topic><topic>Infarction, Middle Cerebral Artery - metabolism</topic><topic>Infarction, Middle Cerebral Artery - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Nervous System Diseases - etiology</topic><topic>Neurology</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - pathology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>Water - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lo, Amy CY</creatorcontrib><creatorcontrib>Chen, Ann YS</creatorcontrib><creatorcontrib>Hung, Victor KL</creatorcontrib><creatorcontrib>Yaw, Lai Ping</creatorcontrib><creatorcontrib>Fung, Maggie KL</creatorcontrib><creatorcontrib>Ho, Maggie CY</creatorcontrib><creatorcontrib>Tsang, Margaret CS</creatorcontrib><creatorcontrib>Chung, Stephen SM</creatorcontrib><creatorcontrib>Chung, Sookja K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of Cerebral Blood Flow & Metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lo, Amy CY</au><au>Chen, Ann YS</au><au>Hung, Victor KL</au><au>Yaw, Lai Ping</au><au>Fung, Maggie KL</au><au>Ho, Maggie CY</au><au>Tsang, Margaret CS</au><au>Chung, Stephen SM</au><au>Chung, Sookja K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet</atitle><jtitle>Journal of Cerebral Blood Flow & Metabolism</jtitle><addtitle>J Cereb Blood Flow Metab</addtitle><date>2005-08-01</date><risdate>2005</risdate><volume>25</volume><issue>8</issue><spage>998</spage><epage>1011</epage><pages>998-1011</pages><issn>0271-678X</issn><eissn>1559-7016</eissn><coden>JCBMDN</coden><abstract>Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ETA antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>15815585</pmid><doi>10.1038/sj.jcbfm.9600108</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of Cerebral Blood Flow & Metabolism, 2005-08, Vol.25 (8), p.998-1011 |
| issn | 0271-678X 1559-7016 |
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| source | SAGE Complete A-Z List; MEDLINE |
| subjects | Animals Aquaporin 4 Aquaporins - biosynthesis Astrocytes - metabolism Astrocytes - ultrastructure Biological and medical sciences Blood Pressure - physiology Blood-Brain Barrier - physiology Blotting, Western Brain - pathology Brain Edema - etiology Brain Edema - metabolism Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Coloring Agents Endothelin A Receptor Antagonists Endothelin B Receptor Antagonists Endothelin-1 - biosynthesis Enzyme-Linked Immunosorbent Assay Evans Blue Fundamental and applied biological sciences. Psychology Glial Fibrillary Acidic Protein - genetics Glial Fibrillary Acidic Protein - metabolism Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy In Situ Hybridization Infarction, Middle Cerebral Artery - complications Infarction, Middle Cerebral Artery - metabolism Infarction, Middle Cerebral Artery - pathology Medical sciences Mice Mice, Transgenic Nervous system (semeiology, syndromes) Nervous System Diseases - etiology Neurology Reperfusion Injury - metabolism Reperfusion Injury - pathology Reverse Transcriptase Polymerase Chain Reaction Vascular diseases and vascular malformations of the nervous system Vertebrates: nervous system and sense organs Water - metabolism |
| title | Endothelin-1 Overexpression Leads to Further Water Accumulation and Brain Edema after Middle Cerebral Artery Occlusion via Aquaporin 4 Expression in Astrocytic End-Feet |
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