Type
Text
Type
Dissertation
Advisor
Tsirka, Stella E | Colognato, Holly | Talmage, David | Robinson, John.
Date
2014-12-01
Keywords
Pharmacology | behavior, microglia, spinal cord injury
Department
Department of Molecular and Cellular Pharmacology.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76526
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Spinal cord injury (SCI) results in the death of neurons, disruption of neuronal connections, demyelination, and inflammation. There are three phases of SCI: Acute (from the time of impact to the first few days post-injury), secondary (hours to weeks), and chronic (months to years). Currently, little can be done to modify the acute phase. Efforts to intervene have focused on the subsequent phases to both promote healing and prevent further damage. In this study I show that the small molecule inhibitor Pifithrin-μ (PFT-μ significantly reduced lesion volume and decreased the presence of inflammatory cells (microglia and macrophages) in the lesion site when applied during the acute phase of SCI. PFT-μ ; polarized microglia to the anti-inflammatory phenotype, and significantly improved motor coordination and posture in SCI animals when combined with the tripeptide microglia inhibitory factor (MIF/TKP), indicating that targeting both the acute and the secondary phase of SCI can facilitate repair and accelerate motor recovery. In a parallel project I examined the behavioral outcomes resulting from elimination of microglia from the brain using a barrage of cognitive and social interaction tests. I show that microglia are dynamic regulators of such behaviors, a finding that confirms their modulatory role in the function of the Central Nervous System both in pathology and physiology. | 105 pages
Recommended Citation
Torres, Luisa, "Microglia in the healthy and diseased central nervous system" (2014). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2433.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2433