Experimental neurology
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Experimental neurology · May 2012
ReviewCell-based transplantation strategies to promote plasticity following spinal cord injury.
Cell transplantation therapy holds potential for repair and functional plasticity following spinal cord injury (SCI). Stem and progenitor cells are capable of modifying the lesion environment, providing structural support and myelination and increasing neurotrophic factors for neuroprotection and endogenous activation. Through these effects, transplanted cells induce plasticity in the injured spinal cord by promoting axonal elongation and collateral sprouting, remyelination, synapse formation and reduced retrograde axonal degeneration. ⋯ Hence, combinatorial stem cell transplantation strategies which could potentially directly address tissue sparing and neuroplasticity in chronic SCI show promise. Rigorous evaluation of combinatorial approaches using stem cell transplantation with appropriate preclinical animal models of SCI is needed to advance therapeutic strategies to the point where clinical trials are appropriate. Given the high patient demand for and clinical trial precedent of cell transplantation therapy, combination stem cell therapies have the promise to provide improved quality of life for individuals, with corresponding socioeconomic benefit.
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Experimental neurology · May 2012
ReviewTreatments to restore respiratory function after spinal cord injury and their implications for regeneration, plasticity and adaptation.
Spinal cord injury (SCI) often leads to impaired breathing. In most cases, such severe respiratory complications lead to morbidity and death. ⋯ This review article will highlight experimental SCI resulting in compromised breathing, the various methods of restoring function after such injury, and some recent findings from our own laboratory. Additionally, it will discuss findings about motor and CNS respiratory plasticity and adaptation with potential clinical and translational implications.
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Experimental neurology · May 2012
ReviewCortical and subcortical compensatory mechanisms after spinal cord injury in monkeys.
This is a review of our investigations into the neuronal mechanisms of functional recovery after spinal cord injury (SCI) in a non-human primate model. In primates, the lateral corticospinal tract (l-CST) makes monosynaptic connections with spinal motoneurons. The existence of direct cortico-motoneuronal (CM) connections has been thought to be the basis of dexterous digit movements, such as precision gripping. ⋯ Such changes in cortical activity in M1 and PMv have been shown to accompany changes in the expressions of plasticity-related genes, such as GAP-43. Changes in the dynamic properties of neural circuits, both at the cortical and subcortical levels, are time-dependent. Multidisciplinary studies to clarify how the changes in the dynamic properties of individual components of the large-scaled networks are coordinated during recovery will help to develop effective therapeutic strategies to recovery from SCI.
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Experimental neurology · May 2012
ReviewTraining and anti-CSPG combination therapy for spinal cord injury.
Combining different therapies is a promising strategy to promote spinal cord repair, by targeting axon plasticity and functional circuit reconnectivity. In particular, digestion of chondroitin sulphate proteoglycans at the site of the injury by the activity of the bacterial enzyme chondrotinase ABC, together with the development of intensive task specific motor rehabilitation has shown synergistic effects to promote behavioural recovery. This review describes the mechanisms by which chondroitinase ABC and motor rehabilitation promote neural plasticity and we discuss their additive and independent effects on promoting behavioural recovery.
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Experimental neurology · May 2012
Comprehensive locomotor outcomes correlate to hyperacute diffusion tensor measures after spinal cord injury in the adult rat.
In adult rats, locomotor deficits following a contusive thoracic spinal cord injury (SCI) are caused primarily by white matter loss/dysfunction at the epicenter. This loss/dysfunction decreases descending input from the brain and cervical spinal cord, and decreases ascending signals in long propriospinal, spinocerebellar and somatosensory pathways, among many others. Predicting the long-term functional consequences of a contusive injury acutely, without knowledge of the injury severity is difficult due to the temporary flaccid paralysis and loss of reflexes that accompany spinal shock. ⋯ In the adult rat model of SCI, we found that hyperacute (<3h post-injury) DTI of the lateral and ventral white matter at the injury epicenter was predictive of both electrophysiological and behavioral (locomotor) recovery at 4 weeks post-injury, despite the presence of flaccid paralysis/spinal shock. Regions of white matter with a minimum axial diffusivity of 1.5 μm(2)/ms at 3h were able to conduct action potentials at 4 weeks, and axial diffusivity within the lateral funiculus was highly predictive of locomotor function at 4 weeks. These observations suggest that acute DTI should be useful to provide functional predictions for spared white matter following contusive spinal cord injuries clinically.