We have found that microglia, resident mononuclear phagocytes of the CNS, play an essential role in the both brain development and in brain pathology. In order to understand and control microgliosis, we will study a particular class of membrane protein found on microglia, the Scavenger Receptor (SR). Previous work from our laboratory as well as unpublished preliminary data show that SRs might regulate a range of phagocytic cell functions that include cell adherence to traumatized brain tissues, clearance of debris, phagocytosis of damaged cells, and production of neurotoxins. To evaluate brain SRs further, we will use such assays as RT-PCR for specific receptor subtypes and ligand binding techniques to provide quantitative measures of receptor numbers and functions. Employing novel methods to monitor SR cell adherence and debris clearance, we will measure to what extent SRs mediate phagocytosis at the time of brain injury. By these studies, we will seek to delineate the precise role for SRs pathways in brain development, wound healing, and immune-mediated attacks upon injured neurons. Strategies to treat inflammation associated with CNS disorders require a basic understanding of reactive gliosis with emphasis upon mechanisms that initiate cellular responses. Defining the SR pathway in the CNS will provide fundamentally important formation that may have value for treatment of neurological diseases.
