Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-07-28

AUTHORS

Ruimin Ge, Daniel Tornero, Masao Hirota, Emanuela Monni, Cecilia Laterza, Olle Lindvall, Zaal Kokaia

ABSTRACT

BackgroundChoroid 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.MethodsAdult 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.ResultsWe 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.ConclusionsOur 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. More... »

PAGES

153

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12974-017-0909-3

DOI

http://dx.doi.org/10.1186/s12974-017-0909-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090910772

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28754163


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47 CX3CR1-GFP
48 ConclusionsOur findings
49 IFNγ expression
50 IL13
51 IL4
52 M2-like macrophages
53 MADCAM1
54 NT5E
55 ResultsWe
56 VCAM1
57 administration
58 animal models
59 artery
60 autologous transplantation
61 behavioral tests
62 blood
63 bone marrow
64 brain
65 brain injury
66 branches
67 cell separation system
68 central nervous system
69 cerebral artery
70 cerebrospinal fluid
71 changes
72 chimeric mice
73 choroid plexus tissue
74 cognitive function
75 cord injury
76 corridor
77 cortical ischemia
78 cortical stroke
79 cytometry
80 days
81 different timepoints
82 disease
83 distal branches
84 donor mice
85 effect
86 entry
87 expression
88 field
89 findings
90 flow cytometry
91 fluid
92 focal cortical ischemia
93 function
94 gene expression
95 hemisphere
96 infarct volume
97 infiltration
98 injury
99 insult
100 ischemia
101 ischemic hemisphere
102 ischemic stroke
103 lateral ventricle
104 macrophages
105 magnetic cell separation system
106 male C57BL/6 mice
107 marrow
108 mediators
109 mice
110 middle cerebral artery
111 migration
112 model
113 monocyte-derived macrophages
114 monocytes
115 motor
116 nervous system
117 new strategy
118 occlusion
119 open field
120 patients
121 permanent occlusion
122 plexus
123 plexus tissue
124 possibility
125 possible mediators
126 post-stroke recovery
127 qPCR
128 recovery
129 recruitment
130 right middle cerebral artery
131 route
132 separation system
133 spinal cord injury
134 strategies
135 stroke
136 system
137 test
138 timepoints
139 tissue
140 traces
141 trafficking
142 transplantation
143 traumatic brain injury
144 upregulation
145 ventricle
146 volume
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