Concise Review: Bridging the Gap: Novel Neuroregenerative and Neuroprotective Strategies in Spinal Cord Injury
Open Access
- 29 April 2016
- journal article
- review article
- Published by Oxford University Press (OUP) in Stem Cells Translational Medicine
- Vol. 5 (7), 914-924
- https://doi.org/10.5966/sctm.2015-0381
Abstract
Spinal cord injuries (SCIs) result in devastating lifelong disability for patients and their families. The initial mechanical trauma is followed by a damaging secondary injury cascade involving proapoptotic signaling, ischemia, and inflammatory cell infiltration. Ongoing cellular necrosis releases ATP, DNA, glutamate, and free radicals to create a cytotoxic postinjury milieu. Long-term regeneration of lost or injured networks is further impeded by cystic cavitation and the formation of an inhibitory glial-chondroitin sulfate proteoglycan scar. In this article, we discuss important neuroprotective interventions currently applied in clinical practice, including surgical decompression, blood pressure augmentation, and i.v. methylprednisolone. We then explore exciting translational therapies on the horizon, such as riluzole, minocycline, fibroblast growth factor, magnesium, and hypothermia. Finally, we summarize the key neuroregenerative strategies of the next decade, including glial scar degradation, Rho-ROCK inhibition, cell-based therapies, and novel bioengineered adjuncts. Throughout, we emphasize the need for combinatorial approaches to this multifactorial problem and discuss relevant studies at the forefront of translation. We conclude by providing our perspectives on the future direction of SCI research. Significance: Spinal cord injuries (SCIs) result in devastating, lifelong disability for patients and their families. This article discusses important neuroprotective interventions currently applied in clinical practice, including surgical decompression, blood pressure augmentation, and i.v. methylprednisolone. Translational therapies on the horizon are discussed, such as riluzole, minocycline, fibroblast growth factor, magnesium, and hypothermia. The key neuroregenerative strategies of the next decade are summarized, including glial scar degradation, Rho-ROCK inhibition, cell-based therapies, and novel bioengineered adjuncts. The need for combinatorial approaches to this multifactorial problem is emphasized, relevant studies at the forefront of translation are discussed, and perspectives on the future direction of SCI research are presented.Keywords
This publication has 128 references indexed in Scilit:
- Generation of induced neurons via direct conversion in vivoProceedings of the National Academy of Sciences of the United States of America, 2013
- Tunable Growth Factor Delivery from Injectable Hydrogels for Tissue EngineeringJournal of the American Chemical Society, 2011
- A Systematic Review of Cellular Transplantation Therapies for Spinal Cord InjuryJournal of Neurotrauma, 2011
- Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potencyProceedings of the National Academy of Sciences of the United States of America, 2010
- Communication via gap junctions underlies early functional and beneficial interactions between grafted neural stem cells and the hostProceedings of the National Academy of Sciences of the United States of America, 2010
- Differentiation of spinal motor neurons from pluripotent human stem cellsNature Protocols, 2009
- Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosisGlia, 2009
- Sequential Expression of Pluripotency Markers during Direct Reprogramming of Mouse Somatic CellsCell Stem Cell, 2008
- Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injuryJournal of Controlled Release, 2006
- Culture and Characterization of Human Embryonic Stem CellsStem Cells and Development, 2004