Effect of Early Weight-Bearing Training on Blood-Spinal Cord Barrier Function in Mice
Advisor:Basso, D. Michele
Keywords:spinal cord injury
blood-spinal cord barrier
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Biomedical Engineering Honors Theses; 2013
Spinal cord injury (SCI) results in a breakdown of the blood-spinal cord barrier (BSCB) that permits a robust inflammatory response responsible for further damage to neural tissue. Neurotoxicity is thought to result from movement of inflammatory cells into the spinal cord through the damaged and permeable blood vessels. Activities such as treadmill training attempt to utilize spinal plasticity to promote recovery, but recent animal studies have shown increased BSCB permeability with early swim training. Exercise-regulated matrix metalloproteinase-9 (MMP-9) is a potent regulator of vascular permeability known to increase acutely following SCI, degrading endothelial tight-junctions. Bloodborne leukocytes may then extravasate into spinal cord tissue. Therefore, the goal of this study was to elucidate whether acute weight-bearing exercise contributes to greater BSCB permeability after SCI through MMP-9 activity. Vascular permeability after moderate/severe (75 kilodynes) contusive SCI at T9 was evaluated in both C57BL/6 wild type (WT) and MMP-9 null (KO) mice. Groups include treadmill-trained and untrained WT and untrained KO mice that survived 1 or 7 days post-injury (dpi). BSCB permeability at injury epicenter was identified using vascular delivery of Evans Blue Dye (EBD) and quantified via fluorescent stereology. Functional recovery was determined using the Basso Mouse Scale for Locomotion (BMS). We demonstrated markedly lower permeability at the lesion with treadmill training than without at 7 dpi in WT mice. In KO mice, we saw much less permeability, as expected. Similar differences remote to the epicenter were not observed. However, functional recovery was much lower following training at 7 dpi. Our results help establish potential cellular effects of activity-based interventions after SCI. Such findings may lead to the development of a more effective timecourse of treatment for human SCI patients to maximize functional recovery.
Related Item:Academic Major: Biomedical Engineering
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