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Eccentric rehabilitation induces white matter plasticity and sensorimotor recovery in chronic spinal cord injury.

Publication ,  Journal Article
Faw, TD; Lakhani, B; Schmalbrock, P; Knopp, MV; Lohse, KR; Kramer, JLK; Liu, H; Nguyen, HT; Phillips, EG; Bratasz, A; Fisher, LC; Deibert, RJ ...
Published in: Exp Neurol
December 2021

Experience-dependent white matter plasticity offers new potential for rehabilitation-induced recovery after neurotrauma. This first-in-human translational experiment combined myelin water imaging in humans and genetic fate-mapping of oligodendrocyte lineage cells in mice to investigate whether downhill locomotor rehabilitation that emphasizes eccentric muscle actions promotes white matter plasticity and recovery in chronic, incomplete spinal cord injury (SCI). In humans, of 20 individuals with SCI that enrolled, four passed the imaging screen and had myelin water imaging before and after a 12-week (3 times/week) downhill locomotor treadmill training program (SCI + DH). One individual was excluded for imaging artifacts. Uninjured control participants (n = 7) had two myelin water imaging sessions within the same day. Changes in myelin water fraction (MWF), a histopathologically-validated myelin biomarker, were analyzed in a priori motor learning and non-motor learning brain regions and the cervical spinal cord using statistical approaches appropriate for small sample sizes. PDGFRα-CreERT2:mT/mG mice, that express green fluorescent protein on oligodendrocyte precursor cells and subsequent newly-differentiated oligodendrocytes upon tamoxifen-induced recombination, were either naive (n = 6) or received a moderate (75 kilodyne), contusive SCI at T9 and were randomized to downhill training (n = 6) or unexercised groups (n = 6). We initiated recombination 29 days post-injury, seven days prior to downhill training. Mice underwent two weeks of daily downhill training on the same 10% decline grade used in humans. Between-group comparison of functional (motor and sensory) and histological (oligodendrogenesis, oligodendroglial/axon interaction, paranodal structure) outcomes occurred post-training. In humans with SCI, downhill training increased MWF in brain motor learning regions (postcentral, precuneus) and mixed motor and sensory tracts of the ventral cervical spinal cord compared to control participants (P < 0.05). In mice with thoracic SCI, downhill training induced oligodendrogenesis in cervical dorsal and lateral white matter, increased axon-oligodendroglial interactions, and normalized paranodal structure in dorsal column sensory tracts (P < 0.05). Downhill training improved sensorimotor recovery in mice by normalizing hip and knee motor control and reducing hyperalgesia, both of which were associated with new oligodendrocytes in the cervical dorsal columns (P < 0.05). Our findings indicate that eccentric-focused, downhill rehabilitation promotes white matter plasticity and improved function in chronic SCI, likely via oligodendrogenesis in nervous system regions activated by the training paradigm. Together, these data reveal an exciting role for eccentric training in white matter plasticity and sensorimotor recovery after SCI.

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Published In

Exp Neurol

DOI

EISSN

1090-2430

Publication Date

December 2021

Volume

346

Start / End Page

113853

Location

United States

Related Subject Headings

  • Young Adult
  • White Matter
  • Spinal Cord Injuries
  • Recovery of Function
  • Psychomotor Performance
  • Neuronal Plasticity
  • Neurology & Neurosurgery
  • Neurological Rehabilitation
  • Middle Aged
  • Mice, Transgenic
 

Citation

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Faw, T. D., Lakhani, B., Schmalbrock, P., Knopp, M. V., Lohse, K. R., Kramer, J. L. K., … Basso, D. M. (2021). Eccentric rehabilitation induces white matter plasticity and sensorimotor recovery in chronic spinal cord injury. Exp Neurol, 346, 113853. https://doi.org/10.1016/j.expneurol.2021.113853
Faw, Timothy D., Bimal Lakhani, Petra Schmalbrock, Michael V. Knopp, Keith R. Lohse, John L. K. Kramer, Hanwen Liu, et al. “Eccentric rehabilitation induces white matter plasticity and sensorimotor recovery in chronic spinal cord injury.Exp Neurol 346 (December 2021): 113853. https://doi.org/10.1016/j.expneurol.2021.113853.
Faw TD, Lakhani B, Schmalbrock P, Knopp MV, Lohse KR, Kramer JLK, et al. Eccentric rehabilitation induces white matter plasticity and sensorimotor recovery in chronic spinal cord injury. Exp Neurol. 2021 Dec;346:113853.
Faw, Timothy D., et al. “Eccentric rehabilitation induces white matter plasticity and sensorimotor recovery in chronic spinal cord injury.Exp Neurol, vol. 346, Dec. 2021, p. 113853. Pubmed, doi:10.1016/j.expneurol.2021.113853.
Faw TD, Lakhani B, Schmalbrock P, Knopp MV, Lohse KR, Kramer JLK, Liu H, Nguyen HT, Phillips EG, Bratasz A, Fisher LC, Deibert RJ, Boyd LA, McTigue DM, Basso DM. Eccentric rehabilitation induces white matter plasticity and sensorimotor recovery in chronic spinal cord injury. Exp Neurol. 2021 Dec;346:113853.
Journal cover image

Published In

Exp Neurol

DOI

EISSN

1090-2430

Publication Date

December 2021

Volume

346

Start / End Page

113853

Location

United States

Related Subject Headings

  • Young Adult
  • White Matter
  • Spinal Cord Injuries
  • Recovery of Function
  • Psychomotor Performance
  • Neuronal Plasticity
  • Neurology & Neurosurgery
  • Neurological Rehabilitation
  • Middle Aged
  • Mice, Transgenic