| 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-micro (PFT-micro) 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-micro 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. |
