Rehabilitative Training in Animal Models of Spinal Cord Injury

Abstract

Rehabilitative motor training is currently one of the most widely used approaches to promote moderate recovery following injuries of the central nervous system. Such training is generally applied in the clinical setting, whereas it is not standard in preclinical research. This is a concern as it is becoming increasingly apparent that neuroplasticity enhancing treatments require training or some form of activity as a co-therapy to promote functional recovery. Despite the importance of training and the many open questions regarding its mechanistic consequences, its use in preclinical animal models is rather limited. Here we review approaches, findings and challenges when training is applied in animal models of spinal cord injury, and we suggest recommendations to facilitate the integration of training using an appropriate study design, into pre-clinical studies.

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

“…Neurodegeneration and dysfunction cause mobility impairment in millions of adults, worldwide. Contemporary regenerative therapies have begun to examine the NMJ as a therapeutic target to restore mobility via reestablished synaptic activity (Natarajan, Sethumadhavan, & Krishnan, ; Torres‐Espin, Beaudry, Fenrich, & Fouad, ). Studies have increasingly recognized terminal SCs as a critical component of the NMJ tripartite and synaptic structure (Figure ), as accumulating evidence illustrates that glia mediate the highly integrated behaviors of adult synapses.…”

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

“…Despite the limited ability of the adult mammalian CNS to regenerate new connections, spontaneous recovery of motor function can occur after human SCI as well as in rodents (Curt, Van Hedel, Klaus, Dietz, & Group, 2008;Hilton et al, 2016;Torres-Espin, Beaudry, Fenrich, & Fouad, 2018). In rodent models of SCI, the re-establishment of stepping after thoracic injury has provided a model for understanding the anatomical and mechanistic basis of spontaneous recovery of motor function (Basso, Beattie, & Bresnahan, 1995;Courtine et al, 2008;Filli, Zorner, Weinmann, & Schwab, 2011;Murray et al, 2010;Rossignol & Frigon, 2011;Schucht, Raineteau, Schwab, & Fouad, 2002).…”

Gabapentinoid treatment promotes corticospinal plasticity and regeneration following murine spinal cord injury

“…In turn, it will be important to determine when medication may be gradually discontinued without compromising any beneficial functional outcome. Whether our treatment strategy may synergize in experimental models of chronic SCI with other promising interventions, such as administration of the membrane-permeable intracellular sigma peptide that binds and inactivates protein tyrosine phosphatase sigma (56,57), or exercise and cardiovascular training (58,59) remains to be tested. Whereas rehabilitative training allows refining and stabilizing newly formed neuronal networks, intensive training early after injury negatively affects network reorganization, leading to recovery failure (60).…”