Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling
Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within th...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/492659 |
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| author | Eunjung Moon Jeong Eun Han Sejin Jeon Jong Hoon Ryu Ji Woong Choi Jerold Chun |
| author_facet | Eunjung Moon Jeong Eun Han Sejin Jeon Jong Hoon Ryu Ji Woong Choi Jerold Chun |
| author_sort | Eunjung Moon |
| collection | DOAJ |
| description | Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain. |
| format | Article |
| id | doaj-art-295ce2d3f7f04d2b8a891adc5c0eebfe |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-295ce2d3f7f04d2b8a891adc5c0eebfe2025-08-20T03:54:47ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/492659492659Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor SignalingEunjung Moon0Jeong Eun Han1Sejin Jeon2Jong Hoon Ryu3Ji Woong Choi4Jerold Chun5Laboratory of Neuropharmacology, College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon 406-799, Republic of KoreaLaboratory of Neuropharmacology, College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon 406-799, Republic of KoreaDepartment of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of KoreaDepartment of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of KoreaLaboratory of Neuropharmacology, College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon 406-799, Republic of KoreaDepartment of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USAInitial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.http://dx.doi.org/10.1155/2015/492659 |
| spellingShingle | Eunjung Moon Jeong Eun Han Sejin Jeon Jong Hoon Ryu Ji Woong Choi Jerold Chun Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling Mediators of Inflammation |
| title | Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling |
| title_full | Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling |
| title_fullStr | Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling |
| title_full_unstemmed | Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling |
| title_short | Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling |
| title_sort | exogenous s1p exposure potentiates ischemic stroke damage that is reduced possibly by inhibiting s1p receptor signaling |
| url | http://dx.doi.org/10.1155/2015/492659 |
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