Journal Article

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

Ahuja, Christopher S., Fehlings, Michael

2016

Overview

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. This review discusses neuroprotective interventions currently applied in clinical practice for the treatment of spinal cord injuries, as well as translational therapies and neuroregenerative strategies in development. The need for combinatorial approaches to this multifactorial problem is emphasized.

• Publisher: AlphaMed Press,Oxford University Press
• Subject: Amyotrophic lateral sclerosis / Animals / Anti-Inflammatory Agents - pharmacology / Anti-Inflammatory Agents - therapeutic use / Apoptosis / Biomaterial / Blood pressure / Cavitation / Cell adhesion & migration / Chondroitin sulfate / Clinical trials / Clinical Trials as Topic / Cytokines / Cytotoxicity / Decompression / Decompression, Surgical / Edema / Enabling Technologies for Cell-Based Clinical Translation / Extracellular matrix / FDA approval / Fibroblast growth factors / Free radicals / Glycoproteins / Hemorrhage / Humans / Hypothermia / Hypothermia, Induced / Inflammation / Injuries / Ischemia / Kinases / Magnesium / Methylprednisolone / Minocycline / Nerve Regeneration - drug effects / Nerve Regeneration - physiology / Neuroglia - drug effects / Neuronal-glial interactions / Neurons / Neuroprotection / Neuroprotective Agents - pharmacology / Neuroprotective Agents - therapeutic use / Neuroregeneration / Regeneration / Sodium Channel Blockers - pharmacology / Sodium Channel Blockers - therapeutic use / Spinal cord injuries / Spinal Cord Injuries - physiopathology / Spinal Cord Injuries - therapy / Spinal cord injury / Stem cell / Studies / Surgeons / Translation / Trauma / Tumor necrosis factor-TNF