Grants and Contracts Details
We have found that pharmacologically maintaining normal mitochondrial bioenergetics after traumatic spinal cord injury (SCI) is an important factor in fostering both neuroprotection and functional recovery. However, no studies have examined the effects of transplanting exogenous mitochondria into spinal cord tissue after traumatic injury in an attempt to normalize overall cellular bioenergetics and spare adjacent tissues. Accordingly, our novel proposal will test whether supplementing exogenous healthy mitochondria, isolated from exogenous or endogenous sources into the injured spinal cord promotes functional neuroprotection. Using a rat model of severe contusion SCI, we have preliminary data showing that allogeneic transgenically-labeled (turboGFP) mitochondria microinjected around the injury site increases overall mitochondrial bioenergetics of the injured cord assessed 24 hrs later. Critically, Oxygen Consumption Rates of mitochondria isolated after acute SCI show trends for increased respiration when transplanted with tGFP mitochondria. Employing specific antibodies to both inner and outer mitochondrial membranes, confocal imaging also reveals that grafted turboGFP mitochondria integrate within naïve and injured host cells. Based on these seminal findings, we propose to conduct a series of transplantation strategies to deliver mitochondria around the injury sites with the ultimate goal of identifying a potential autologous cell source (i.e., leg muscles) to prevent secondary tissue injury that is mediated, in large part, by mitochondrial dysfunction. This project has translational potential wherein mitochondria, notably autologous, can be transplanted around the SCI site to spare penumbral tissues.
|Effective start/end date||4/1/16 → 4/30/19|
- National Institute of Neurological Disorders & Stroke: $413,875.00
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