Spinal cord Injury (SCI) produces a devastating syndrome characterized by loss of motor function, hyper- reflexia, spasticity, and pain. The long-term goal of SCI therapy is to promote adaptive spinal plasticity for restoration of function while limiting maladaptive plasticity that results in hyper-reflexia, spasticity and intractable pain. Recent research has indicated that both adaptive and maladaptive CNS plasticity can occur at the level of the spinal cord to dictate recovery of function. However, the specific conditions that promote adaptive versus maladaptive spinal plasticity in SCI are not well-understood. Our central hypothesis is that maladaptive spinal plasticity is predicated upon aberrant peripheral stimulation in the acute phase of SCI. This hypothesis has strong clinical/translational relevance, as epidemiological studies indicate that peripheral injuries are prevalent comorbidities in human SCI. Our preliminary experimental data suggest that peripheral nociceptive stimulation delivered caudal to a complete SCI lesion produces maladaptive spinal plasticity that manifests as tactile hyper-reflexia and spasticity. Similar effects are observed wih nerve injury below the SCI lesion. Our findings link these effects to specific alterations in glutamate receptor-mediated synaptic plasticity in the spinal ventral horn, providing a novel therapeutic target for restoration of function after SCI.
The Aims expand on the preliminary data to: 1) test the specific impact of nociceptive stimulation below SCI on hyper- reflexia/spasticity, 2) evaluate synaptic mechanisms involved, and 3) test an intervention for combating maladaptive plasticity to promote adaptive recovery in a clinically-relevant model of contusive SCI. The proposed project has implications for therapeutic targeting in polytraumatic SCI-a prevalent clinical presentation where CNS lesions are accompanied with peripheral injuries.
Spinal cord injury (SCI) is a devastating syndrome often characterized by comorbid damage to extremities. The proposed project explores the spinal cellular mechanisms engaged by concomitant peripheral injuries during SCI, and tests their contribution to spasticity/hyper-reflexia and chronic spinal recovery impairments. These studies may provide novel targets for improving recovery after SCI.
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