Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Gregory Dekaban

Second Advisor

Dr. Arthur Brown

Third Advisor

Dr. Bosco Chan

Abstract

Administration of a monoclonal antibody to the CDI ld∕CD18 integrin results in significant functional recovery in rodent models of spinal cord injury (SCI). This treatment selectively delays the influx of monocyte-derived hematogenous macrophages (hM0), suggesting that hM0 exhibit neurodegenerative or neuroprotective effects depending upon the temporal microenvironment of the SCI lesion. hM0 and microglial macrophages (mM0) are indistinguishable; hence, their roles in response to SCI remain unclear. Using SCI lys-EGFP-ki mice that enable distinction of EGFP+ hM0 from EGFP^ mM0, we demonstrate that both populations peak in the lesion at 7d post-SCI. The ‘classical inflammatory’ monocytes∕hM0 and ‘non-classical resident’ monocytes∕hM0 respond to the acute (ld, 3d, 7d) and chronic (14d, 6wks) stages of SCI, respectively. We report the depletion of a possibly novel blood subset in response to SCI that expresses monocyte and dendritic cell markers. Our study provides new insights for the mechanism of dichotomous response of hM0 to SCI.

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