At present, little hope is offered to those with impaired olfactory function. The long-term objectives of this project are to investigate the mechanisms regulating neural regeneration and to develop strategies to enhance recovery and restore function following injury or disease. An established model of olfactory nerve injury will be used to investigate the role of MMPs following nerve injury and recovery processes during the regeneration and rewiring of olfactory axons in the olfactory bulb. Matrix metalloproteinases (MMPs) are regulators of the extracellular remodeling that occurs in reparative, homeostatic and metastatic processes. This study will determine if MMPs contribute to mechanisms that regulate the response to injury and regenerative and reparative processes in the olfactory system. Changes in MMP levels and their localization within the olfactory bulb will be measured at different time points from the onset of nerve injury, through degeneration, regeneration and recovery. It is hypothesized that MMP9 plays an important role during the early response to injury by regulating the amount of inflammation, gliosis, and scar formation and that MMP2 enhances recovery by facilitating the reinnervation and rewiring of axons in the olfactory bulb. MMP knockout mice will be used to determine if MMPs are required for normal recovery processes. Experiments represent a new direction and a novel approach that will begin to address the mechanisms of olfactory system regeneration and repair at the molecular level. The olfactory system may provide the key to understanding recovery processes in the central nervous system. Findings could lead to the development of new treatment strategies to help improve or restore olfactory function following injury or disease, and lay the groundwork for the future development of treatment strategies directed at modulating the activity of MMPs. ? ? ?
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