Experimental neurology
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This article reviews stem cell-based strategies for spinal cord injury repair, and practical issues concerning their translation to the clinic. Recent progress in the stem cell field includes clinically compliant culture conditions and directed differentiation of both embryonic stem cells and somatic stem cells. ⋯ We review the practical considerations and risks that must be addressed before human treatments can begin. With a growing understanding of these practical issues, stem cell biology, and spinal cord injury pathophysiology, stem cell-based therapies are moving closer to clinical application.
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Experimental neurology · Feb 2008
ReviewEffect of spinal cord injury on the neural regulation of respiratory function.
Injury at any level of the spinal cord can impair respiratory motor function. Indeed, complications associated with respiratory function are the number one cause of mortality in humans following spinal cord injury (SCI) at any level of the cord. This review is aimed at describing the effect of SCI on respiratory function while highlighting the recent advances made by basic science research regarding the neural regulation of respiratory function following injury. ⋯ The approaches used to induce motor recovery in the respiratory system are similar to other studies that examine recovery of locomotor function after SCI. These include strategies to initiate regeneration of damaged axons, to reinnervate paralyzed muscles with peripheral nerve grafts, to use spared neural pathways to induce motor function, and finally, to initiate mechanisms of neural plasticity within the spinal cord to increase motoneuron firing. The ultimate goals of this research are to restore motor function to previously paralyzed respiratory muscles and improve ventilation in patients with SCI.
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Experimental neurology · Feb 2008
Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3.
Increased chondroitin sulfate proteoglycan (CSPG) expression in the vicinity of a spinal cord injury (SCI) is a primary participant in axonal regeneration failure. However, the presence of similar increases of CSPG expression in denervated synaptic targets well away from the primary lesion and the subsequent impact on regenerating axons attempting to approach deafferented neurons have not been studied. Constitutively expressed CSPGs within the extracellular matrix and perineuronal nets of the adult rat dorsal column nuclei (DCN) were characterized using real-time PCR, Western blot analysis and immunohistochemistry. ⋯ Application of chondroitinase ABC or neurotrophin-3-expressing lentivirus in the DCN partially overcame this inhibition. When the treatments were combined, entrance by regenerating axons into the DCN was significantly augmented. These results demonstrate both an additional challenge and potential treatment strategy for successful functional pathway reconstruction after SCI.
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Experimental neurology · Feb 2008
A re-assessment of the effects of a Nogo-66 receptor antagonist on regenerative growth of axons and locomotor recovery after spinal cord injury in mice.
This study was undertaken as part of the NIH "Facilities of Research-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeated a study reporting that treatment with the NgR antagonist peptide NEP1-40 results in enhanced growth of corticospinal and serotonergic axons and enhanced locomotor recovery after thoracic spinal cord injury. Mice received dorsal hemisection injuries at T8 and then received either NEP1-40, Vehicle, or a Control Peptide beginning 4-5 h (early treatment) or 7 days (delayed treatment) post-injury. ⋯ In a second experiment comparing NEP-treated and Vehicle controls, there were no statistically significant differences on any of the functional outcome measures. Together, our results suggest that treatment with NEP1-40 created a situation that was slightly more conducive to axon regeneration or sprouting. Enhanced functional recovery was not seen consistently with the different functional assessments, however.