Abstract
The high clinical relevance of models of incomplete cervical spinal cord injury (SCI) creates a need to address the spontaneous neuroplasticity that underlies changes in functional activity that occur over time after SCI. There is accumulating evidence supporting long projecting propriospinal neurons as suitable targets for therapeutic intervention after SCI, but focus has remained primarily oriented toward study of descending pathways. Long ascending axons from propriospinal neurons at lower thoracic and lumbar levels that form inter-enlargement pathways are involved in forelimb-hindlimb coordination during locomotion and are capable of modulating cervical motor output. We used non-invasive magnetic stimulation to assess how a unilateral cervical (C5) spinal contusion might affect transmission in intact, long ascending propriospinal pathways, and influence spinal cord plasticity. Our results show that transmission is facilitated in this pathway on the ipsilesional side as early as 1 week post-SCI. We also probed for descending magnetic motor evoked potentials (MMEPs) and found them absent or greatly reduced on the ipsilesional side as expected. The frequency-dependent depression (FDD) of the H-reflex recorded from the forelimb triceps brachii was bilaterally decreased although Hmax/Mmax was increased only on the ipsilesional side. Behaviorally, stepping recovered, but there were deficits in forelimb–hindlimb coordination as detected by BBB and CatWalk measures. Importantly, epicenter sparing correlated to the amplitude of the MMEPs and locomotor recovery but it was not significantly associated with the inter-enlargement or segmental H-reflex. In summary, our results indicate that complex plasticity occurs after a C5 hemicontusion injury, leading to differential changes in ascending vs. descending pathways, ipsi- vs. contralesional sides even though the lesion was unilateral as well as cervical vs. lumbar local spinal networks.
Highlights
As the majority of human injuries are incomplete and occur at the cervical level, experimental models of cervical spinal cord injury (SCI) are highly clinically relevant
Long ascending propriospinal axons are likely candidates to be involved in coupling and coordination between the cervical and lumbar central pattern generators (CPGs; Miller et al, 1973a,b; English et al, 1985) as the rhythmicity in cervical segments can be driven by the lumbar CPG (Juvin et al, 2005)
To confirm the magnetic interenlargement responses (MIER) results, electrical stimulation of the sciatic was performed in five contused animals 2 weeks after SCI and in three normal animals. This time point was chosen because our results showed that MIER responses were already modulated at 1 week post-SCI
Summary
As the majority of human injuries are incomplete and occur at the cervical level (www.sci-info-pages.com), experimental models of cervical SCI are highly clinically relevant. Propriospinal neurons have recently emerged as attractive targets for treatment after spinal cord injury (SCI) as regeneration over long distances is very limited. They have the potential to form new intraspinal circuits (Bareyre et al, 2004; Courtine et al, 2008) and regenerate (Fenrich and Rose, 2009) after SCI, giving these pathways a high potential of success if integrated in a comprehensive combinatory treatment such as cellular transplant and neurotrophin delivery (Jordan and Schmidt, 2002; Conta and Stelzner, 2004; Fouad et al, 2005)
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