Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury

Abstract

Smaller spinal cord injuries often allow some degree of spontaneous behavioral improvements because of structural rearrangements within different descending fiber tracts or intraspinal circuits. In this study, we investigate whether rehabilitative training of the forelimb (forced limb use) influences behavioral recovery and plastic events after injury to a defined spinal tract, the corticospinal tract (CST). Female adult Lewis rats received a unilateral CST injury at the brainstem level. Use of the contralateral impaired forelimb was either restricted, by a cast, or forced, by casting the unimpaired forelimb immediately after injury for either 1 or 3 weeks. Forced use of the impaired forelimb was followed by full behavioral recovery on the irregular horizontal ladder, whereas animals that could not use their affected side remained impaired. BDA (biotinylated dextran amine) labeling of the intact CST showed lesion-induced growth across the midline where CST collaterals increased their innervation density and extended fibers toward the ventral and the dorsal horn in response to forced limb use. Gene chip analysis of the denervated ventral horn revealed changes in particular for growth factors, adhesion and guidance molecules, as well as components of synapse formation suggesting an important role for these factors in activity-dependent intraspinal reorganization after unilateral CST injury.

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

“…For example, swim training initiated acutely following thoracic SCI was less efficient compared to a 2-week onset, and it was paralleled by a significantly increased extravasation in and around the injury site [51]. 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.…”

“…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].…”

Unilateral Pyramidotomy of the Corticospinal Tract in Rats for Assessment of Neuroplasticity-inducing Therapies

“…Most of these show a functional motor deficit 1 week after injury. Currently, most studies described in the literature only perform behavioural testing up to 42 days 4,11,13,20,21 , or for a shorter time 3,18,22 . We have performed behavioural testing for a prolonged period of time and have seen essentially full recovery of motor function 8 weeks post pyramidotomy for some of the behavioural tests, except the Montoya staircase test and the horizontal ladder test.…”

“…Other options are to aspirate the lesion site with a tipped glass suction pipette as described in Zhou et al 2003 29 . A fine tungsten wire can also be used to cut the tract 22 . An alternative to pyramidotomy is to cut the cervical C3 dorsal CST unilaterally and then to cut with a ventral approach the ipsilesional C2 ventral part of the CST 18 .…”

Impact of White Matter Damage After Stroke

“…As observed in lesion experiments, intensive rehabilitation allowed animals with damage of corticospinal tracts to recover considerably (Maier et al, 2008). In these animals, collateral fibres increased their innervation density and extended toward the ventral and dorsal horn in response to forced limb use.…”