The long-term goal of the Reynolds Family Spine Laboratory is to discover novel therapies to improve the functional outcomes of chronic and acute spinal cord injury (SCI) and diseases of the central nervous system that lead to paralysis. Current research uses animal models of spinal cord contusion injury and inflammation, genetically modified mice and neuronal/glial cultures and co-cultures to study neuro-immune interactions, the cross-talk between neurons and glia, mechanisms of neuronal protection, survival and death, axonal regeneration and recovery of motor, sensory and bladder function after SCI.
The degenerative versus protective and regenerative roles of immune system-related cells and activated glia are investigated. The goal is to define mechanisms that enhance the beneficial potential and limit the detrimental effects of inflammatory cells and glia in order to unravel new therapeutic targets. Currently, the laboratory is investigating how toll-like receptor (TLR) ligands modulate inflammation and glial activation after acute and chronic spinal cord contusion injury, with especial emphasis on TLR9 agonists and antagonists. It is proposed that some TLR ligands modulate the inflammatory response to injury to create a more permissive environment for cell survival and axonal regeneration.
Impaired bladder function and neuropathic pain are co-morbidities associated with chronic spinal cord injury. In addition to recovery of locomotor function, the laboratory is investigating new strategies that can lead to the improvement of bladder control and chronic pain in spinal cord injury. The research team is performing studies on the modulation of bladder control and neuropathic pain by TLR9 ligands.
Another topic of interest is the mechanisms underlying the survival and death of spinal cord neurons. Our earlier studies indicated that plasma membrane calcium ATPase 2 (PMCA2), a calcium pump, is essential for the survival of spinal cord neurons. The expression of this pump in spinal cord neurons is reduced after injury and inflammation. We reported a link between decreased PMCA2 expression and a reduction in collapsing response mediator protein 1 (CRMP1), a member of a family that is essential for cytokeletal stability and dendritic integrity. Ongoing investigations are determining the mechanisms downstream to PMCA2 and CRMP1, which mediate the survival versus death of spinal cord neurons in injury and inflammation. The goal is to define novel targets for neuroprotection in pathological conditions of the spinal cord.
The development of new surgical approaches to alleviate the outcome of spinal cord injury is another focus of our research. The laboratory is determining whether durotomy and duraplasty improve recovery of locomotor function and histopathological features of spinal cord injury.