Respiration following spinal cord injury: Evidence for human neuroplasticity

Abstract

Respiratory dysfunction is one of the most devastating consequences of cervical spinal cord injury (SCI) with impaired breathing being a leading cause of morbidity and mortality in this population. However, there is mounting experimental and clinical evidence for moderate spontaneous respiratory recovery, or “plasticity”, after some spinal cord injuries. Pre-clinical models of respiratory dysfunction following SCI have demonstrated plasticity at neural and behavioral levels that result in progressive recovery of function. Temporal changes in respiration after human SCI have revealed some functional improvements suggesting plasticity paralleling that seen in experimental models – a concept that has been previously under-appreciated. While the extent of spontaneous recovery remains limited, it is possible that enhancing or facilitating neuroplastic mechanisms may have significant therapeutic potential. The next generation of treatment strategies for SCI and related respiratory dysfunction should aim to optimize these recovery processes of the injured spinal cord for lasting functional restoration.

Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

“…Although spinal injury results in multiple changes in the spinal microenvironment, we hypothesize that removal of descending synaptic inputs to phrenic motor neurons triggers mechanisms of inactivity-induced plasticity to promote spontaneous ipsilateral functional recovery and contralateral compensatory plasticity. For example, within days-weeks following high cervical SCI, an initially paralyzed hemidiaphragm caudal to injury often spontaneously (partially) recovers in humans (Axen et al, 1985; Hoh et al, 2013; McKinley et al, 1996; Oo et al, 1999; Strakowski et al, 2007) and rodents (Baussart et al, 2006; El-Bohy et al, 1998; Fuller et al, 2006; Golder et al, 2011; Golder and Mitchell, 2005; Lane et al, 2009; Vinit et al, 2007), although the extent of this spontaneous recovery depends on injury severity. This return of ipsilateral diaphragm activity post-injury may be due to remodeling of phrenic circuits (Darlot et al, 2012; Goshgarian, 2009; Lane et al, 2009) or strengthening of spared ipsilateral pathways (Vinit et al, 2008; Vinit and Kastner, 2009), possibly via mechanisms of iPMF.…”

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

“…Evidence for functional respiratory plasticity was first demonstrated over a century ago using a lateral C2 hemisection (C2Hx) (Porter, 1895), which has since become the most frequently used model of respiratory dysfunction and plasticity following SCI (Goshgarian, 2003a; Hoh et al, 2013; Vinit and Kastner, 2009b; Warren and Alilain, 2014). This type of injury compromises direct (monosynaptic) projections from the ventral respiratory column in the medulla to ipsilateral phrenic motoneurons (Ellenberger and Feldman, 1988; Ellenberger et al, 1990; Keomani et al, 2014; Lane et al, 2009b; Lane et al, 2008; Vinit and Kastner, 2009a), and results in an ipsilateral hemidiaphragm paralysis (Figure 1).…”

Cortical reorganization after spinal cord injury: Always for good?

“…Finally, spinal cord injury not only affects evoked sensorimotor activity, but also slows down cortical spontaneous EEG activity (Tran et al, 2004; Boord et al, 2008; Wydenkeller et al, 2009). It is worth mention that an important literature exists on central nervous system plasticity after spinal cord injury in the context of breathing (Sharma et al, 2012; Hoh et al, 2013) and bladder function (Merrill et al, 2013; de Groat and Yoshimura, 2012). However, this plasticity is mostly subcortical (but see Zempleni et al, 2010), and will not be further discussed here.…”