Injection of neural progenitor cells attenuates decrease in level of connexin 43 in brain capillaries after cerebral ischemia

•Cerebral ischemia induced a sustained decrease in the level of connexin 43 in the isolated brain capillaries.•The injection of NPCs after cerebral ischemia increased the level of connexin 43 in the isolated brain capillaries.•Some of the injected NPCs migrated into the blood vessels in the peri-inf...

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Veröffentlicht in:Neuroscience letters 2013-05, Vol.543, p.152-156
Hauptverfasser: Moriyama, Yoshiyuki, Takagi, Norio, Itokawa, Chisa, Tanonaka, Kouichi
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container_title Neuroscience letters
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creator Moriyama, Yoshiyuki
Takagi, Norio
Itokawa, Chisa
Tanonaka, Kouichi
description •Cerebral ischemia induced a sustained decrease in the level of connexin 43 in the isolated brain capillaries.•The injection of NPCs after cerebral ischemia increased the level of connexin 43 in the isolated brain capillaries.•Some of the injected NPCs migrated into the blood vessels in the peri-infarct area. Although functional disruption of the cerebrovasculature, which is called the “neurovascular unit (NVU)”, may lead to amplification of ischemia-induced injury, changes in the gap junctional proteins within the NVU and their pathophysiological roles after brain injury remain controversial. We previously demonstrated that the intravenous injection of neural progenitor cells (NPCs) have therapeutic potential for improving the spatial learning dysfunction and depression-like behaviors observed after cerebral ischemia. In this study, we investigated whether severe cerebral ischemia would alter the expression of gap junctional proteins in isolated brain capillaries and examined the effect of intravenous injection of NPCs on the levels of these proteins. Cerebral ischemia induced a sustained decrease in the level of the gap junctional protein connexin 43 (Cx43) in the isolated brain capillaries, whereas the level of aquaporin 4 (AQP-4) was transiently increased. The injection of NPCs increased the level of Cx43 compared that of vehicle in the microsphere embolism (ME) rats, suggesting this decrease to be a possible mechanism for disruption of the astrocyte-endothelial cell interface within the NVU without causing any changes in the level of AQP-4 and N-cadherin. We also demonstrated that some of the intravenously injected NPCs migrated into the blood vessels in the peri-infarct area. These results suggest that the intravenous injection of the NPCs would remodel the NVU after severe cerebral ischemia, which remodeling might be associated with functional improvement following the NPC injection.
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Although functional disruption of the cerebrovasculature, which is called the “neurovascular unit (NVU)”, may lead to amplification of ischemia-induced injury, changes in the gap junctional proteins within the NVU and their pathophysiological roles after brain injury remain controversial. We previously demonstrated that the intravenous injection of neural progenitor cells (NPCs) have therapeutic potential for improving the spatial learning dysfunction and depression-like behaviors observed after cerebral ischemia. In this study, we investigated whether severe cerebral ischemia would alter the expression of gap junctional proteins in isolated brain capillaries and examined the effect of intravenous injection of NPCs on the levels of these proteins. Cerebral ischemia induced a sustained decrease in the level of the gap junctional protein connexin 43 (Cx43) in the isolated brain capillaries, whereas the level of aquaporin 4 (AQP-4) was transiently increased. The injection of NPCs increased the level of Cx43 compared that of vehicle in the microsphere embolism (ME) rats, suggesting this decrease to be a possible mechanism for disruption of the astrocyte-endothelial cell interface within the NVU without causing any changes in the level of AQP-4 and N-cadherin. We also demonstrated that some of the intravenously injected NPCs migrated into the blood vessels in the peri-infarct area. 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These results suggest that the intravenous injection of the NPCs would remodel the NVU after severe cerebral ischemia, which remodeling might be associated with functional improvement following the NPC injection.</description><subject>Animals</subject><subject>Aquaporin 4 - pharmacology</subject><subject>Astrocytes - metabolism</subject><subject>Brain - blood supply</subject><subject>Brain - metabolism</subject><subject>Brain capillaries</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Brain Ischemia - physiopathology</subject><subject>Cadherins - metabolism</subject><subject>Capillaries - metabolism</subject><subject>Cell Movement</subject><subject>Cells, Cultured</subject><subject>Cerebral ischemia</subject><subject>Connexin 43 - metabolism</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Gap junction</subject><subject>Neural progenitor cells</subject><subject>Neural Stem Cells - pathology</subject><subject>Neural Stem Cells - physiology</subject><subject>Neural Stem Cells - transplantation</subject><subject>Rats</subject><subject>Rats, Transgenic</subject><subject>Rats, Wistar</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcuKFDEUDaI47egfiNTSTbU3r65kI8jgY2DAja7DrdQtTZNOtUlq0IX_booeXQqXBC7nkXPC2EsOew788Oa4T7RGqnsBXO6hjZaP2I6bQfSDHcRjtgMJqpdWwRV7VsoRADTX6im7ElIbqa3asd-36Ui-hiV1y9w1xYyxO-flG6VQl9x5irF0WCulFSuVbiKfCQt1IXWR7iluPL-kRD_bRsltP2Zsp8dziBFzaCycK21imcbNIBT_nU4Bn7MnM8ZCLx7ua_b1w_svN5_6u88fb2_e3fVeCVN75WdtUCEiGKEFTEqgHY2f_DzIiVscFUkBB4QDN0IMdrSD5nK2xoD1k5DX7PVFtyX7sVKp7tSe0KJhomUtjktlwapWXYOqC9TnpZRMszvncML8y3FwW_Hu6C7Fu614B220bLRXDw7reKLpH-lv0w3w9gKglvM-UHbFB0qeppDbB7hpCf93-ANIhJe2</recordid><startdate>20130524</startdate><enddate>20130524</enddate><creator>Moriyama, Yoshiyuki</creator><creator>Takagi, Norio</creator><creator>Itokawa, Chisa</creator><creator>Tanonaka, Kouichi</creator><general>Elsevier Ireland Ltd</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>7X8</scope></search><sort><creationdate>20130524</creationdate><title>Injection of neural progenitor cells attenuates decrease in level of connexin 43 in brain capillaries after cerebral ischemia</title><author>Moriyama, Yoshiyuki ; 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subjects Animals
Aquaporin 4 - pharmacology
Astrocytes - metabolism
Brain - blood supply
Brain - metabolism
Brain capillaries
Brain Ischemia - metabolism
Brain Ischemia - pathology
Brain Ischemia - physiopathology
Cadherins - metabolism
Capillaries - metabolism
Cell Movement
Cells, Cultured
Cerebral ischemia
Connexin 43 - metabolism
Endothelial Cells - metabolism
Endothelium, Vascular - metabolism
Gap junction
Neural progenitor cells
Neural Stem Cells - pathology
Neural Stem Cells - physiology
Neural Stem Cells - transplantation
Rats
Rats, Transgenic
Rats, Wistar
title Injection of neural progenitor cells attenuates decrease in level of connexin 43 in brain capillaries after cerebral ischemia
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