Reaching training in rats with spinal cord injury promotes plasticity and task specific recovery

Abstract

In the current study we examined the effects of training in adult rats with a cervical spinal cord injury (SCI). One group of rats received 6 weeks of training in a single pellet reaching task immediately after injury, while a second group did not receive training. Following this period changes in cortical levels of BDNF and GAP-43 were analysed in trained and untrained animals and in a group with training but no injury. In another group of rats, functional recovery was analysed in the reaching task and when walking on a horizontal ladder. Thereupon, the cortical forelimb area was electrophysiologically examined using micro-stimulation followed by tracing of the lesioned corticospinal tract (CST). We found that trained rats improved substantially in the reaching task, when compared to their untrained counterparts. Trained rats however, performed significantly worse with their injured forelimb when walking on a horizontal ladder. In parallel to the improved recovery in the trained task, we found that the cortical area where wrist movements could be evoked by micro-stimulation expanded in trained rats in comparison to both untrained and uninjured rats. Furthermore, collateral sprouting of lesioned CST fibres rostral to the injury was increased in trained rats. Post-injury training was also found to increase cortical levels of GAP-43 but not BDNF. In conclusion we show that training of a reaching task promotes recovery of the trained task following partial SCI by enhancing plasticity at various levels of the central nervous system (CNS), but may come at the cost of an untrained task.

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

“…This result has not been found in rats with cervical SCI and different training (reaching) onsets [43]. In a similar scenario, we have only observed negative effects on an untrained task with early onset of training [45], an effect perhaps masked in the functional outcome of the trained task. Another critical complication following SCI is autonomic dysreflexia, which has been proposed to be exaggerated by treadmill training [52], but this is not commonly reported after treadmill training in individuals with SCI.…”

“…More recent studies using cervical lesion models, with the functional emphasis on fine motor control of hand/paw function, confirmed these ideas and related plasticity at various levels of the CNS to the recovery of motor function. Not surprisingly, the mechanisms read like a list found under spontaneous plasticity including the up-regulation of growth/plasticity associated factors ( [43]; reviewed in Krajacic et al [35] and Vaynman et al [44]) and sprouting of lesioned fibers [45], as well as changes in spinal circuitries [17,38,39,[46][47][48], cortical maps [35,45], and in neuronal properties [49,50].…”

“…For example, cats with complete SCI transections trained to walk on a treadmill had difficulties in standing in contrast to cats trained to stand, which performed worse in walking than untrained cats [53,56]. Likewise, rats with cervical SCI trained in a reaching task showed deficits in crossing a horizontal ladder [45] or increased activity induced by environmental enrichment promoted recovery in untrained tasks, but interfered with the training in reaching tasks [57]. These observations suggest that the injured CNS will be rewired task specifically, probably at the cost of other tasks.…”

Chondroitinase ABC Combined with Neurotrophin NT-3 Secretion and NR2D Expression Promotes Axonal Plasticity and Functional Recovery in Rats with Lateral Hemisection of the Spinal Cord

“…The number of crossing axons was normalized for each animal by dividing the number of axon crossings by the total number of fibers traced in the right and left lateral funiculi and the length of the section studied (Girgis et al, 2007;García-Alías et al, 2009). For the reticulospinal axons we counted processes crossing the gray-white matter boundary divided by the number of axons, as above.…”

“…Among these therapies, blockade of inhibitory NogoA (Maier and Schwab, 2006), digestion of chondroitin sulfate proteoglycans (CSPGs) , neurotrophin delivery (Lu and Tuszynski, 2008), intervention in axon growth signaling pathways (Shearer et al, 2003) and physical rehabilitation (Girgis et al, 2007), have been shown to promote regeneration and/or sprouting of damaged and undamaged axons leading to functional repair. However, none of these interventions by itself gives full recovery of function.…”