Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier
Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by r...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1279385/full |
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| author | Yang Chen Yang Chen Lin Lin Lin Lin Mohammad Iqbal H. Bhuiyan Kai He Kai He Roshani Jha Shanshan Song Shanshan Song Shanshan Song Victoria M. Fiesler Victoria M. Fiesler Gulnaz Begum Gulnaz Begum Yan Yin Dandan Sun Dandan Sun Dandan Sun |
| author_facet | Yang Chen Yang Chen Lin Lin Lin Lin Mohammad Iqbal H. Bhuiyan Kai He Kai He Roshani Jha Shanshan Song Shanshan Song Shanshan Song Victoria M. Fiesler Victoria M. Fiesler Gulnaz Begum Gulnaz Begum Yan Yin Dandan Sun Dandan Sun Dandan Sun |
| author_sort | Yang Chen |
| collection | DOAJ |
| description | Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated. We induced ischemic stroke in C57BL/6J mice via transient middle cerebral artery occlusion which led to reduction of cerebral blood flow and infarct stroke. At 1–7 days post-stroke, we detected time-dependent increase in the ChP blood-CSF barrier permeability to albumin, tight-junction damage, and dynamic changes of SPAK-NKCC1 protein complex, a key ion transport regulatory system for CSF production and clearance. A transient loss of SPAK protein complex but increased phosphorylation of the SPAK-NKCC1 complex was observed in both lateral ventricle ChPs. Most interestingly, stroke also triggered elevation of proinflammatory Lcn2 mRNA and its protein as well as infiltration of anti-inflammatory myeloid cells in ChP at day 5 post-stroke. These findings demonstrate that ischemic strokes cause significant damage to the ChP blood-CSF barrier, contributing to neuroinflammation in the subacute stage. |
| first_indexed | 2024-03-09T10:42:30Z |
| format | Article |
| id | doaj.art-571221ae1b8640e0af02a7d828f9bb53 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-09T10:42:30Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-571221ae1b8640e0af02a7d828f9bb532023-12-01T12:32:28ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-12-011710.3389/fncel.2023.12793851279385Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrierYang Chen0Yang Chen1Lin Lin2Lin Lin3Mohammad Iqbal H. Bhuiyan4Kai He5Kai He6Roshani Jha7Shanshan Song8Shanshan Song9Shanshan Song10Victoria M. Fiesler11Victoria M. Fiesler12Gulnaz Begum13Gulnaz Begum14Yan Yin15Dandan Sun16Dandan Sun17Dandan Sun18Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesThe School of Pharmacy, University of Texas at El Paso, El Paso, TX, United StatesDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, United StatesResearch Service, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, United StatesDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, United StatesResearch Service, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, United StatesNeuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated. We induced ischemic stroke in C57BL/6J mice via transient middle cerebral artery occlusion which led to reduction of cerebral blood flow and infarct stroke. At 1–7 days post-stroke, we detected time-dependent increase in the ChP blood-CSF barrier permeability to albumin, tight-junction damage, and dynamic changes of SPAK-NKCC1 protein complex, a key ion transport regulatory system for CSF production and clearance. A transient loss of SPAK protein complex but increased phosphorylation of the SPAK-NKCC1 complex was observed in both lateral ventricle ChPs. Most interestingly, stroke also triggered elevation of proinflammatory Lcn2 mRNA and its protein as well as infiltration of anti-inflammatory myeloid cells in ChP at day 5 post-stroke. These findings demonstrate that ischemic strokes cause significant damage to the ChP blood-CSF barrier, contributing to neuroinflammation in the subacute stage.https://www.frontiersin.org/articles/10.3389/fncel.2023.1279385/fullblood-CSF barrierLcn2Na+ -K+ -Cl– cotransporterneuroinflammationSPAK |
| spellingShingle | Yang Chen Yang Chen Lin Lin Lin Lin Mohammad Iqbal H. Bhuiyan Kai He Kai He Roshani Jha Shanshan Song Shanshan Song Shanshan Song Victoria M. Fiesler Victoria M. Fiesler Gulnaz Begum Gulnaz Begum Yan Yin Dandan Sun Dandan Sun Dandan Sun Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier Frontiers in Cellular Neuroscience blood-CSF barrier Lcn2 Na+ -K+ -Cl– cotransporter neuroinflammation SPAK |
| title | Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier |
| title_full | Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier |
| title_fullStr | Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier |
| title_full_unstemmed | Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier |
| title_short | Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier |
| title_sort | transient ischemic stroke triggers sustained damage of the choroid plexus blood csf barrier |
| topic | blood-CSF barrier Lcn2 Na+ -K+ -Cl– cotransporter neuroinflammation SPAK |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1279385/full |
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