Can eccentric rehabilitation induce myelin plasticity below spinal cord injury in mice?
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Date
2023-12
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The Ohio State University
Abstract
Demyelination after contusive spinal cord injuries (SCI) causes neurological deficits including motor and sensory dysfunction. New research showed that plasticity occurs in myelin where learning complex skills greatly increases development of new oligodendrocytes (McKenzie, 2014). However, therapy-induced white matter changes after neurotrauma remains largely unknown. Some natural axon remyelination occurs around the SCI without rehabilitation, peaking around five weeks (Pukos, 2019). Recently, our lab showed that eccentric downhill treadmill walking induced white matter plasticity well-above the injury, in the cervical cord, after chronic thoracic SCI (Faw, 2021). Here, we examine the extent of myelin plasticity due to downhill training well-below the SCI in the lumbar cord where locomotion is organized. We hypothesize that there will be a robust degree of myelin plasticity in the lumbar dorsal columns, which will exhibit a positive relationship with the recovery of locomotor and sensory functions. Adult male and female mice (n=18) were randomly assigned to three groups; naïve (n=6), untrained SCI (n=6) with contusion (75 kilodyne) at T9 spinal column, and eccentric downhill treadmill trained (dhTM) SCI (n=6). To determine eccentric-induced white matter plasticity, we used PDGFRα-CreERT2: mT/mG mice to express green fluorescent protein (GFP) on newly differentiated oligodendrocyte cells upon tamoxifen administration. The injection occurred 29 days after SCI, and seven days prior to downhill training. The 13-day dhTM regimen used with 4 training bouts, each 5 min in length separated by 5 min rest breaks, on a 10% declined TM. Downhill training caused an increase in new mature oligodendrocytes (GFP+/CC1+) in the lumbar dorsal columns compared to the untrained groups (p=0.05). An increase in new mature oligodendrocytes after dhTM also showed a strong, positive correlation with recovery in sensory function (r=0.827; p=0.006). These findings may offer valuable insight into the application of eccentric rehabilitation as a therapy to treat white matter loss in the lumbar cord stemming from chronic SCI, ultimately improving locomotor and sensory function in people currently living with SCI.
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Keywords
Recovery of function, Downhill Treadmill Training, Oligodendrocytes, Myelin Plasticity