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Stem Cells Transl Med. 2016 Jul;5(7):914-24. doi: 10.5966/sctm.2015-0381. Epub 2016 Apr 29.

Concise Review: Bridging the Gap: Novel Neuroregenerative and Neuroprotective Strategies in Spinal Cord Injury.

Author information

1
Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
2
Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada McEwen Centre for Regenerative Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada Department of Surgery, University of Toronto, Toronto, Ontario, Canada Spine Program, University of Toronto, Toronto, Ontario, Canada McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, Ontario, Canada Michael.Fehlings@uhn.ca.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02163876.

KEYWORDS:

Biomaterial; Neuroprotection; Neuroregeneration; Spinal cord injury; Stem cell; Trauma

PMID:
27130222
PMCID:
PMC4922857
DOI:
10.5966/sctm.2015-0381
[Indexed for MEDLINE]
Free PMC Article

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