Consequences of differential macrophage activation after spinal cord trauma
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The Ohio State University / OhioLINK
2007
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1177686458 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu11776864582021-08-03T05:52:04Z Consequences of differential macrophage activation after spinal cord trauma Longbrake, Erin E. spinal cord injury macrophage microglia CNS inflammation chemokine fractalkine CX3CR1 <p>Spinal cord injury (SCI) elicits a robust macrophage response comprised of microglia and hematogenous cells. Collectively referred to as CNS macrophages, these have been postulated to play both detrimental and protective roles after CNS trauma. Concrete evidence supporting either hypothesis is limited, however, due to the dynamic microenvironment elicited by trauma and the limited tools available to study these cells.</p> <p>In vitro studies would assist dissection of the complex SCI lesion by simplifying the identification of physiologically important macrophage stimuli. Further, they should yield insight into the neurotoxic or neurotrophic potential of individual CNS macrophage populations. For models to be relevant, however, they must accurately mimic the in vivo situation. Thus, using laser capture microdissection and real time PCR, we defined the inductive potential of hematogenous SCI macrophages in vivo. We compared this phenotype to that of three commonly-studied primary macrophage populations and determined that bone marrow derived, but not resident or elicited peritoneal macrophages, accurately modeled hematogenous SCI macrophages and would be appropriate for future in vitro work.</p> <p>Another limitation to the study of CNS macrophages is that although microglia and monocyte derived macrophages likely play distinct roles after injury, these cells are morphologically indistinguishable. We identified CX3CR1 as a ubiquitous microglial marker that is expressed by only a small fraction of peripheral macrophages. This marker holds great potential for differentiating functions of ontogenetically distinct CNS macrophages.</p> <p>Signaling via CX3CR1 is an important component of microglial activation; in some models, loss of this receptor heightens microglial-mediated neurotoxicity. We found that in other types of CNS injury, CX3CR1 deficiency had no effect or was neuroprotective. Indeed, CX3CR1-deficient mice had significantly improved recovery from SCI; this was associated with a decreased inflammatory response. It is likely that components of the injury milieu determine the phenotype of CX3CR1-/- cells. In vitro, CX3CR1-deficient macrophages and microglia had a diminished inflammatory response to LPS and to serum. Thus, the neuroprotective effects of disrupting CX3CR1 after SCI may be due to macrophages/microglia responding less robustly to hemorrhage and endogenous TLR4 ligands. Further investigation may lead to treatments effective for SCI and other CNS diseases in which the blood brain barrier is compromised.</p> 2007-05-17 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1177686458 http://rave.ohiolink.edu/etdc/view?acc_num=osu1177686458 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. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
spinal cord injury macrophage microglia CNS inflammation chemokine fractalkine CX3CR1 |
| spellingShingle |
spinal cord injury macrophage microglia CNS inflammation chemokine fractalkine CX3CR1 Longbrake, Erin E. Consequences of differential macrophage activation after spinal cord trauma |
| author |
Longbrake, Erin E. |
| author_facet |
Longbrake, Erin E. |
| author_sort |
Longbrake, Erin E. |
| title |
Consequences of differential macrophage activation after spinal cord trauma |
| title_short |
Consequences of differential macrophage activation after spinal cord trauma |
| title_full |
Consequences of differential macrophage activation after spinal cord trauma |
| title_fullStr |
Consequences of differential macrophage activation after spinal cord trauma |
| title_full_unstemmed |
Consequences of differential macrophage activation after spinal cord trauma |
| title_sort |
consequences of differential macrophage activation after spinal cord trauma |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2007 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1177686458 |
| work_keys_str_mv |
AT longbrakeerine consequencesofdifferentialmacrophageactivationafterspinalcordtrauma |
| _version_ |
1719426833559060480 |