Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury
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The Ohio State University / OhioLINK
2013
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1385386981 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu13853869812021-08-03T06:20:37Z Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury Brautigam, Bryan A. Immunology Neurobiology Neurosciences spinal cord injury inflammation microglia macrophage CD200 Spinal cord injury (SCI) is a debilitating condition resulting in permanent loss of sensation and paralysis with a lifetime estimated health cost ranging from one million to four million dollars. After SCI, a complex cellular response exacerbates the initial damage and the spinal cord fails to regenerate damaged neurons. Various immune cells are recruited to the site of injury, including resident microglia and macrophages, which are known for their dual and conflicting role of facilitating neural growth/regeneration and pathogenesis. Targeting the inflammatory immune response could serve to reduce secondary damage and create a permissive environment for axonal regeneration.One mechanism for regulating myeloid cells is through the neuroimmune regulatory proteins, CD200 and CD200R, which contribute to neuron-mediated inhibition of myeloid cell activation and pro-inflammatory signaling cascades. CD200 is expressed on a wide variety of cells throughout the body, including neurons, while CD200R is primarily expressed on microglia and macrophages. While a regulatory role of CD200/CD200R is evident in many central nervous system (CNS) disease models, it is not known if this mechanism contributes to neuroprotection following trauma to the CNS. By understanding how CD200 regulates myeloid cells after SCI, we hope to reduce inflammation with the goal of creating an environment conducive for axonal regeneration.The overall hypothesis is that CD200 is downregulated after SCI resulting in decreased CD200R activation on macrophages and microglia causing increasedinflammation. The goal is to determine if delivery of a soluble CD200R agonist after SCI will reduce inflammation and secondary damage. We determined that CD200 is highly expressed within the gray matter and to some extent within the white matter, while CD200R is expressed at extremely low levels on resting microglia. After lesioning the dorsal roots, sciatic nerve and corticospinal tract, we determined that CD200 expression is maintained after injury or not expressed by these specific neurons. Injection of CD200R antagonist into the nai¨ve spinal cord resulted in microglial activation. Following contusion SCI, CD200 expression is decreased within the lesion, while CD200R increases with the time course of macrophage migration into the injured spinal cord. In the crush injury model, CD200 expression is maintained in the spared gray matter rostral and caudal to the lesion and within the lesion, while the glial scar does not express CD200. Administration of CD20Fc to bone marrow derived macrophages does not reduce LPS induced increases in nitric oxide production.Based on our results, CD200 does not appear to play a significant role in reversing myeloid cell activation under the specific conditions tested. While antagonizing CD200R in the spinal cord resulted in microglial activation, the presence of CD200 or CD200R agonists was not sufficient to overcome activation in the presence of activating stimuli. We believe that CD200R agonists would not be sufficient to overcome the excessive number of inflammatory stimuli present after SCI, therefore targeting CD200R for treatment in locations with fewer inflammatory stimuli or before macrophage activation may prove successful. 2013 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1385386981 http://rave.ohiolink.edu/etdc/view?acc_num=osu1385386981 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Immunology Neurobiology Neurosciences spinal cord injury inflammation microglia macrophage CD200 |
| spellingShingle |
Immunology Neurobiology Neurosciences spinal cord injury inflammation microglia macrophage CD200 Brautigam, Bryan A. Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury |
| author |
Brautigam, Bryan A. |
| author_facet |
Brautigam, Bryan A. |
| author_sort |
Brautigam, Bryan A. |
| title |
Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury |
| title_short |
Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury |
| title_full |
Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury |
| title_fullStr |
Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury |
| title_full_unstemmed |
Examining the Regulation of Inflammation through CD200 and CD200R Following Spinal Cord Injury |
| title_sort |
examining the regulation of inflammation through cd200 and cd200r following spinal cord injury |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2013 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1385386981 |
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AT brautigambryana examiningtheregulationofinflammationthroughcd200andcd200rfollowingspinalcordinjury |
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1719435036677111808 |