Harnessing neuroplasticity for clinical applications.

Sir, The recent review article ‘Harnessing neuroplasticity for clinical applications’ (Cramer et al., 2011) is in many respects an impressively sophisticated summary of current knowledge of CNS plasticity and its potential translation to important new therapeutic applications. However, this otherwise excellent article has one very major omission: anyone reading it who did not already know better would assume that neuroplasticity essentially ends at the foramen magnum. Apart from several brief references to corticospinal tract plasticity, there is no mention of spinal cord plasticity, of its importance in sensorimotor function, and of the rapidly growing evidence that appropriate engagement and guidance of spinal cord plasticity could play a major role in restoring useful function after spinal cord injuries, strokes and other trauma or disease. A major area of active and successful research that applies directly to the subject of the article, ‘Harnessing neuroplasticity for clinical applications,’ is not addressed. A full review of activity-dependent spinal cord plasticity and its potential clinical applications would be nearly as lengthy as Cramer et al. (2011). The relevant information comprises at least six substantial bodies of data, three coming from pathological situations or reduced preparations and three coming from normal life. These six areas are briefly summarized and illustrated here. First, the long-term changes in spinal cord function that develop after injury or disease disrupt supraspinal control have been recognized for at least a century (Riddoch, 1917; Brodal, 1981; Hiersemenzel et al., 2000; Wolpaw and Tennissen, 2001). Indeed, long-term survival after spinal cord injury depends on meticulous bladder, bowel and skin-care regimens that serve to moderate this plasticity. Perhaps, the best early laboratory evidence of activity-dependent spinal cord plasticity was Anna DiGiorgio’s (1929, 1942) demonstration that a short period of abnormal descending activity produced by a hemicerebellar lesion causes a lasting change in spinal cord function. Figure 1A illustrates this striking phenomenon. Secondly, laboratory studies over the past 60 years have demonstrated that the isolated adult mammalian spinal cord has a remarkable capacity for activity-dependent plasticity. Shurrager and Dykman (1951) showed in cats with complete spinal cord transections that the isolated spinal cord could learn to walk better with training. Over the past 30 years, this work has been greatly extended: anatomical and physiological mechanisms are being defined; and potential clinical applications are being explored (Courtine et al., 2009; Edgerton and Roy, 2009; Rossignol and Frigon, 2011; Rossignol et al., 2011) (Fig. 1B). Over the same period, other studies have described both classical and operant conditioning in the isolated spinal cord (Durkovic and Damianopoulos, 1986; Grau et al., 2006). Thirdly, much of the excitement now surrounding the possibilities for restoring function after spinal cord injury concerns methods for inducing, facilitating and guiding spinal cord plasticity. These include methods: (i) to reduce scarring and facilitate axon regrowth; (ii) to replace lost neurons and preserve those that remain; (iii) to encourage other adaptive responses to injury; and (iv) to re-establish functionally effective synaptic connections (Fouad et al., 2011; Marsh et al., 2011). These methods seek to enable, augment and guide the spinal cord’s intrinsic capacities for plasticity (e.g. Fig. 1C). Fourthly, both human and animal studies show that the acquisition of basic behaviours such as locomotion and withdrawal from pain depends on perinatal spinal cord plasticity, which is guided by the brain and sensory input (Myklebust et al., 1982, 1986; Eyre et al., 2001; Martin et al., 2004; Schouenborg, 2008). doi:10.1093/brain/aws017 Brain 2012: Page 1 of 4 | e1