Disuse plasticity limits spinal cord injury recovery
Use-dependent plasticity after spinal cord injury (SCI) enhances neuromotor function, however, the optimal timing to initiate rehabilitation remains controversial. To test impacts of early disuse, we established a rodent model of transient hindlimb suspension in acute phase SCI. Early disuse in the first 2-week after SCI undermined recovery on open-field locomotion, kinematics, and swim tests even after 6-week of normal gravity reloading. Early disuse produced chronic spinal circuit hyper-excitability in H-reflex and interlimb reflex tests. Quantitative synaptoneurosome analysis of lumboventral spinal cords revealed shifts in AMPA receptor (AMPAR) subunit GluA1 localization and serine 881 phosphorylation, reflecting enduring synaptic memories of early disuse stored in the spinal cord. Automated confocal analysis of motoneurons revealed persistent shifts toward GluA2-lacking, calcium-permeable AMPARs in disuse subjects. Unsupervised machine learning associated multidimensional synaptic changes with persistent recovery deficits in SCI. The results argue for early aggressive rehabilitation to prevent disuse plasticity that limits SCI recovery.
Authors
- Toshiki Tazoe (ORCID: https://orcid.org/0000-0002-7304-9951)
- Michael S. Beattie (ORCID: https://orcid.org/0000-0001-9463-3631)
- Adam R. Ferguson (ORCID: https://orcid.org/0000-0001-7102-1608)
- Makoto Hamanoue (ORCID: https://orcid.org/0000-0003-4054-1875)
- Cristian F. Guandique
- J. Russell Huie (ORCID: https://orcid.org/0000-0001-5594-4277)
- Sakae Tanaka (ORCID: https://orcid.org/0000-0001-9210-9414)
- Carlos de Almeida (ORCID: https://orcid.org/0000-0001-9997-8719)
- Kazuhito Morioka (ORCID: https://orcid.org/0000-0001-5407-8178)
- Jenny Haefeli (ORCID: https://orcid.org/0000-0002-3546-728X)
- Toru Ogata (ORCID: https://orcid.org/0000-0001-9011-8640)
- Jacqueline C. Bresnahan
- Kentaro Hayakawa
- Rentaro Okazaki
- Takashi Endoh
Institutions
- Toho University (JP)
- University of California, San Francisco (US)
- Uekusa Gakuen University (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- University of Tokyo Hospital (JP)
- Saitama Red Cross Hospital (JP)
- Tokyo Metropolitan Geriatric Hospital (JP)
- Neurological Surgery (US)
- National Rehabilitation Center for Persons with Disabilities (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- iScience
- Published
- 2025-03-08
- DOI
- https://doi.org/10.1016/j.isci.2025.112180
- Primary Topic
- Spinal Cord Injury Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Veterans Affairs
- Craig H. Neilsen Foundation
- Mitsui Sumitomo Insurance Welfare Foundation
- Wings for Life
- National Institutes of Health
- Japan Society for the Promotion of Science