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In Vivo Observations of Resident Microglia and Blood Derived Macrophages in the Brain and Spinal Cord

Evans, Teresa Ann

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
Microglia and macrophages are two phagocytic cell types that found in the Central Nervous System (CNS). Microglia are present in the normal CNS and play a role in both homeostasis and disease while macrophages are not present in large numbers in the healthy CNS. After an insult, microglia become activated and macrophages infiltrate into the tissue from the circulation. Both of these cell types express many of the same markers and display similar morphology, making them so difficult to distinguish that they are often lumped into one group. Here, we observed microglia and macrophages in the healthy CNS and in several different injury models. First, we describe interactions of both microglia and macrophages with damaged axons in traumatic spinal cord injury. Previously, it has been shown that damaged axons die back from the center of a spinal cord lesion over the first few days after injury by an immune mediated process. We have shown that this dieback occurs by loss of axonal material from the damaged end of the axon after contact with CX3CR1 GFP expressing, bone marrow derived, macrophages but not after contact with resident microglia independent of the CCR2 chemokine receptor. Second, we investigated a possible role for microglia in the presentation of antigen across the blood brain barrier. Current thought maintains that antigen presentation from within the CNS is completed without direct interaction between microglia and T-cells. We have observed microglial projections that leave the compartment defined by the blood brain barrier and extend into blood vessels, representing a potential route for antigen presentation to circulating T-cells. These projections increase in number in an autoimmune condition, experimental autoimmune encephalomyelitis, and did not increase in cases of sterile trauma or tumor infiltration, presumably due to differences in activation of antigen presentation in these models. Together, these descriptions identify previously unknown differences between microglia and macrophages and propose a new function for microglia. As these two separate cell populations are further investigated and separate identities established, this understanding may lead to more targeted therapies for CNS disorders.
Jerry Silver, Dr. (Advisor)
Alex Huang, Dr. (Advisor)
Gary Landreth, Dr. (Committee Chair)
Lynn Landmesser, Dr. (Committee Member)
George Dubyak, Dr. (Committee Member)
189 p.

Recommended Citations

Citations

  • Evans, T. A. (2014). In Vivo Observations of Resident Microglia and Blood Derived Macrophages in the Brain and Spinal Cord [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1396399768

    APA Style (7th edition)

  • Evans, Teresa. In Vivo Observations of Resident Microglia and Blood Derived Macrophages in the Brain and Spinal Cord. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1396399768.

    MLA Style (8th edition)

  • Evans, Teresa. "In Vivo Observations of Resident Microglia and Blood Derived Macrophages in the Brain and Spinal Cord." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1396399768

    Chicago Manual of Style (17th edition)