Knowledge Bank

Spinal cord injury (SCI) can have devastating results, including debilitating loss of mobility. In human SCI patients, locomotor training on a level treadmill is often used to improve motor function. Animal studies investigating more effective therapies have shown downhill training to enhance recovery [1]. This effect is due to increased delivery of eccentric sensory feedback to the central nervous system (CNS). An eccentric contraction is a controlled lengthening contraction where muscles met with resistance send signals to the CNS that determine the amount of muscle output. Downhill treadmill exercise increases levels of eccentric feedback and has been shown to improve walking ability after SCI, producing gait patterns that nearly match naїve animals [1]. Eccentric feedback can be delivered in varying dosages and intervals, similar to a drug. Dose can be modulated utilizing different treadmill elevations that provide minimal (uphill) and maximal (downhill) amounts of eccentric feedback at walking and running speeds. It remains unclear how task-specific eccentric exercise differentially impacts the microenvironment within the spinal cord. Here, we test the hypothesis that different forms of sensory feedback produced during task-specific training paradigms differentially influence blood spinal cord barrier (BSCB) permeability and microglial reactivity. In order to identify what changes result from task-specific exercise training, mice with intact nervous systems were utilized in this study. Nineteen uninjured C57BL/6 mice were randomized into 5 groups: downhill walk (n=4), downhill run (n=3), uphill walk (n=4), uphill run (n=4), and unexercised sedentary (n=4). Microglial reactivity was measured in the spinal cord with iba-1 labeling. A vascular tracer, Evans blue dye (EBD), was used to measure BSCB stability. Analysis of these two outcome measures unexpectedly revealed uninjured exercised mice to display evidence of BSCB permeability in lamina X and the intermediate lamina (lamina VII), with greatest permeability in downhill walking animals. We hypothesize that task-specific exercises causes BSCB permeability by increasing angiogenesis within lamina X, a region known to be involved in incline walking as well transmitting nociceptive and mechanoreceptive information, and the intermediate lamina, the location of locomotor central pattern generators (CPG) [2-5]. Evidence of vessel growth was analyzed using Ly6C immunohistochemical staining of vasculature in lumbar tissue. Results of this study can be used to optimize exercise therapies for SCI patients.