Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury

Abstract

Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals. One strategy with demonstrated therapeutic potential is the use of treatments that increase neural and muscular activity (e.g. locomotor training, neural and muscular stimulation) and promote plasticity. With a focus on respiratory function post-SCI, this review will discuss advances in the use of neural interfacing strategies and activity-based treatments, and highlights some recent results from our own research.

Spinal cord injury in infancy: activity-based therapy impact on health, function, and quality of life in chronic injury

“…7d). Pulmonary function testing [23][24][25][26] 3-5 years post-initial AB-LT at 6-8 years of age revealed normal capacity [5,6]. These results suggest the stability and durability of improved respiratory function years following completion of an intense program of AB-LT.…”

Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord

“…[71][72][73][74] From a more translational perspective, a growing area of interest in the field of SCI and rehabilitation is the use of acute, intermittent hypoxia (IH) as a way to facilitate plasticity in respiratory (and nonrespiratory) motor circuits. 70,75 This neurorehabilitative approach has shown success in both pre-clinical 76 and clinical 77,78 studies, and its effects are thought to be mediated (in part) by supraspinal, serotonergic projections. A hypoxic episode stimulates serotonin release into the spinal cord 79 and an increase in the electrophysiological activity of mature, FSC transplanted neurons.…”

Cell biology of spinal cord injury and repair

“…Such approaches have also shown benefit in regulating breathing (148) or autonomic functions such as bladder control (149). On the other hand, spontaneous synapse reorganization in spared but reactive neural tissue can lead to maladaptive consequences such as muscle spasticity (25), autonomic dysreflexia (26), or neuropathic pain (27,28).…”