Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke
Abstract Background Choroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer’s disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after is...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-017-0909-3 |
| _version_ | 1811301433532743680 |
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| author | Ruimin Ge Daniel Tornero Masao Hirota Emanuela Monni Cecilia Laterza Olle Lindvall Zaal Kokaia |
| author_facet | Ruimin Ge Daniel Tornero Masao Hirota Emanuela Monni Cecilia Laterza Olle Lindvall Zaal Kokaia |
| author_sort | Ruimin Ge |
| collection | DOAJ |
| description | Abstract Background Choroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer’s disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after ischemic stroke is unknown. Methods Adult male C57BL/6 mice were subjected to focal cortical ischemia by permanent occlusion of the distal branch of the right middle cerebral artery. Choroid plexus tissues were collected and analyzed for Vcam1, Madcam1, Cx3cl1, Ccl2, Nt5e, and Ifnγ expression at different timepoints after stroke using qPCR. Changes of MDMs in CP and cerebrospinal fluid (CSF) at 1 day and 3 days after stroke were analyzed using flow cytometry. Infiltration of MDMs into CP and CSF were validated using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. CD115+ monocytes were isolated using a magnetic cell separation system from bone marrow of Cx3cr1-GFP or wild-type C57BL/6 donor mice. The freshly isolated monocytes or M2-like MDMs primed in vitro with IL4 and IL13 were stereotaxically injected into the lateral ventricle of stroke-affected mice to trace for their migration into ischemic hemisphere or to assess their effect on post-stroke recovery using open field, corridor, and active avoidance behavioral tests. Results We found that CP responded to cortical stroke by upregulation of gene expression for several possible mediators of MDM trafficking and, concomitantly, MDMs increased in CP and cerebrospinal fluid (CSF). We then confirmed that MDMs infiltrated from blood into CP and CSF after the insult using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. When MDMs were directly administered into CSF following stroke, they homed to the ischemic hemisphere. If they had been primed in vitro prior to their administration to become M2-like macrophages, they promoted post-stroke recovery of motor and cognitive function without influencing infarct volume. Conclusions Our findings suggest the possibility that autologous transplantation of M2-like MDMs into CSF might be developed into a new strategy for promoting recovery also in patients with stroke. |
| first_indexed | 2024-04-13T07:08:45Z |
| format | Article |
| id | doaj.art-1e7aac8b30324376bc069258443c6ee3 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T07:08:45Z |
| publishDate | 2017-07-01 |
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| series | Journal of Neuroinflammation |
| spelling | doaj.art-1e7aac8b30324376bc069258443c6ee32022-12-22T02:56:56ZengBMCJournal of Neuroinflammation1742-20942017-07-0114111510.1186/s12974-017-0909-3Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after strokeRuimin Ge0Daniel Tornero1Masao Hirota2Emanuela Monni3Cecilia Laterza4Olle Lindvall5Zaal Kokaia6Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University HospitalLaboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University HospitalLaboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University HospitalLaboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University HospitalLaboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University HospitalLaboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University HospitalLaboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University HospitalAbstract Background Choroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer’s disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after ischemic stroke is unknown. Methods Adult male C57BL/6 mice were subjected to focal cortical ischemia by permanent occlusion of the distal branch of the right middle cerebral artery. Choroid plexus tissues were collected and analyzed for Vcam1, Madcam1, Cx3cl1, Ccl2, Nt5e, and Ifnγ expression at different timepoints after stroke using qPCR. Changes of MDMs in CP and cerebrospinal fluid (CSF) at 1 day and 3 days after stroke were analyzed using flow cytometry. Infiltration of MDMs into CP and CSF were validated using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. CD115+ monocytes were isolated using a magnetic cell separation system from bone marrow of Cx3cr1-GFP or wild-type C57BL/6 donor mice. The freshly isolated monocytes or M2-like MDMs primed in vitro with IL4 and IL13 were stereotaxically injected into the lateral ventricle of stroke-affected mice to trace for their migration into ischemic hemisphere or to assess their effect on post-stroke recovery using open field, corridor, and active avoidance behavioral tests. Results We found that CP responded to cortical stroke by upregulation of gene expression for several possible mediators of MDM trafficking and, concomitantly, MDMs increased in CP and cerebrospinal fluid (CSF). We then confirmed that MDMs infiltrated from blood into CP and CSF after the insult using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. When MDMs were directly administered into CSF following stroke, they homed to the ischemic hemisphere. If they had been primed in vitro prior to their administration to become M2-like macrophages, they promoted post-stroke recovery of motor and cognitive function without influencing infarct volume. Conclusions Our findings suggest the possibility that autologous transplantation of M2-like MDMs into CSF might be developed into a new strategy for promoting recovery also in patients with stroke.http://link.springer.com/article/10.1186/s12974-017-0909-3StrokeInflammationChoroid plexusTransplantationFunctional recovery |
| spellingShingle | Ruimin Ge Daniel Tornero Masao Hirota Emanuela Monni Cecilia Laterza Olle Lindvall Zaal Kokaia Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke Journal of Neuroinflammation Stroke Inflammation Choroid plexus Transplantation Functional recovery |
| title | Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke |
| title_full | Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke |
| title_fullStr | Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke |
| title_full_unstemmed | Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke |
| title_short | Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke |
| title_sort | choroid plexus cerebrospinal fluid route for monocyte derived macrophages after stroke |
| topic | Stroke Inflammation Choroid plexus Transplantation Functional recovery |
| url | http://link.springer.com/article/10.1186/s12974-017-0909-3 |
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