Shevtsova Natalia A, Lockhart Andrew B, Rybak Ilya A, Magnuson David S K, Danner Simon M
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
Department of Neurological Surgery, University of Louisville School of Medicine, Health Sciences Campus, Louisville, KY, USA.
bioRxiv. 2025 May 22:2025.05.17.654682. doi: 10.1101/2025.05.17.654682.
Rats exhibit significant recovery of locomotor function following incomplete spinal cord injuries, albeit with altered gait expression and reduced speed and stepping frequency. These changes likely result from and give insight into the reorganization within spared and injured spinal circuitry. Previously, we developed computational models of the mouse spinal locomotor circuitry controlling speed-dependent gait expression (Danner et al. 2017; Zhang et al. 2022). Here, we adapted these models to the rat and used the adapted model to explore potential circuit-level changes underlying altered gait expression observed after recovery from two different thoracic spinal cord injuries (lateral hemisection and contusion) that have roughly comparable levels of locomotor recovery (Danner et al., 2023). The model reproduced experimentally observed gait expression before injury and after recovery from lateral hemisection and contusion, and suggests two distinct, injury-specific mechanisms of recovery. First, recovery after lateral hemisection required substantial functional restoration of damaged descending drive and long propriospinal connections, suggesting compensatory plasticity through formation of detour pathways. Second, recovery after a moderate midline contusion predominantly relied on reorganization of spared sublesional networks and altered control of supralesional cervical circuits, compensating for weakened propriospinal and descending pathways. These observations suggest that symmetrical (contusion) and asymmetrical (lateral hemisection) injuries induce distinct types of plasticity in different regions of the spinal cord, indicating that effective therapeutic strategies may benefit from targeting specific circuits according to injury symmetry.
大鼠在不完全脊髓损伤后表现出显著的运动功能恢复，尽管步态表现改变，速度和步频降低。这些变化可能源于脊髓未受损和受损神经回路的重组，并为其提供了深入了解。此前，我们开发了控制速度依赖步态表现的小鼠脊髓运动神经回路的计算模型（丹纳等人，2017年；张等人，2022年）。在此，我们将这些模型应用于大鼠，并使用经过调整的模型来探索从两种不同的胸段脊髓损伤（侧半横切和挫伤）恢复后观察到的步态表现改变背后潜在的神经回路水平变化，这两种损伤的运动恢复水平大致相当（丹纳等人，2023年）。该模型再现了损伤前以及从侧半横切和挫伤恢复后的实验观察到的步态表现，并提出了两种不同的、损伤特异性的恢复机制。首先，侧半横切后的恢复需要受损下行驱动和长脊髓 propriospinal 连接的大量功能恢复，这表明通过形成迂回通路实现了代偿性可塑性。其次，中度中线挫伤后的恢复主要依赖于未受损的损伤下神经回路的重组以及损伤上颈段神经回路控制的改变，以补偿脊髓 propriospinal 和下行通路的减弱。这些观察结果表明，对称性（挫伤）和不对称性（侧半横切）损伤在脊髓的不同区域诱导了不同类型的可塑性，这表明有效的治疗策略可能受益于根据损伤对称性靶向特定神经回路。
