Effect of Acute Physical Interventions on Pathophysiology and Recovery After Spinal Cord Injury: A Comprehensive Review of the Literature

Abstract

Physical rehabilitation is essential for enhancing recovery in individuals with spinal cord injury (SCI); however, aside from early surgical intervention and hemodynamic management, there are no proven interventions for promoting recovery in the acute phase. In general, early rehabilitation is considered beneficial, but optimal parameters and potential contraindications for implementing rehabilitation at very early time points are unclear. Moreover, clinical trials to date are limited to studies initiating rehabilitation 2 weeks after injury and later. To address these gaps, this article reviews the preclinical literature on physical interventions initiated within the first 8 days postinjury. Effects of early rehabilitation on molecular and structural nervous system changes, behavioral function, and body systems are considered. Most studies utilized treadmill or cycle training as the primary intervention. Treadmill training initiated within the first 3 days and terminated by 1 week after injury worsened autonomic function, inflammation, and locomotor outcomes, while swim training during this period increased microvascular dysfunction. In contrast, lower-intensity rehabilitation such as reach training, ladder training, or voluntary wheel or ball training showed benefits when implemented during the first 3 days. Rehabilitation initiated at 4 days postinjury was also associated with enhanced motor recovery. Cycling appears to have the greatest risk-benefit ratio; however, the effects of cycle training in the first 3 days were not investigated. Overall, research suggests that lower intensity or voluntary rehabilitation during the hyperacute phase is more appropriate until at least 4 days postinjury, at which point higher-intensity activity becomes safer and more beneficial for recovery.

Keywords: Acute intervention; Early mobilization; Rehabilitation; Spinal cord injury.

Conflict of interest statement

Conflict of Interest

The authors have nothing to disclose.

Figures

Fig. 1.

Effects of acute physical interventions on functional recovery from SCI. Recovery was broken down into 12 areas encompassing molecular, structural, systemic, and functional responses to acute physical activity. This figure highlights important takeaways and indicates whether overall effects on each system were positive, negative, or neutral based on the placement of either a check, x, or dash, respectively, in each box. 4E-BP1, eukaryotic translation initiation factor 4E binding protein 1; 5HT, serotonergic axon; AKT, protein kinase B; BDNF, brain-derived neurotrophic factor; BOS, base of support; CST, corticospinal tract; Eif- 4E, eukaryotic translation initiation factor 4E; GABA, gamma-aminobutyric acid; GAD65/67, glutamate decarboxylase 65/67; GDNF, glial cell-derived neurotrophic factor; GFAP, glial fibrillary acidic protein; H-Reflex, Hoffmann’s reflex; H/M ratio, Hwave/ M-wave; IBA1, ionized calcium-binding adapter molecule 1; IGF1, insulin-line growth factor 1; IGFBP4/5, insulin-like growth factor binding protein 4/5; KCC2, potassium-chloride cotransporter 2; NKCC1, sodium-potassium-chloride cotransporter 1; miR, micro ribonucleic acid; mRNA, messenger ribonucleic acid; mTOR, mechanistic (or mammalian) target of rapamycin; myoD, myogenic differentiation 1; NT3, neurotrophin-3; P-Erk1/2, phosphorylated extracellular signal-regulated kinase 1/2; SCI, spinal cord injury; TGFα, transforming growth factor alpha; TrkB, tropomyosin receptor kinase B; TrkC, tropomyosin receptor kinase C.

Fig. 2.

Rehabilitation timing and parameters for hyperacute SCI recovery. Recommendations for rehabilitation training parameters in the hyperacute (0- to 3-day postinjury) and acute (4- to 8-day postinjury) phases of recovery are presented. Due to the differences in biological response and risk at each time point, different parameters for training type, dosage, and intensity are recommended.