Abstract
Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, in combination with other factors and cell transplantations, for repairing the injured spinal cord. As studies of recent decades strongly suggest that combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.
Highlights
Medical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, Spinal Cord and Brain Injury Research, Indiana University School of Medicine, Indianapolis, IN 47450, USA
glial cell line-derived neurotrophic factor (GDNF)’s targets in the central nervous system (CNS) and peripheral nervous system (PNS), as well as the administration of GDNF gene therapy for motoneuron protection were highlighted in a review by Bohn [30]
One of the earliest studies to report GDNF-induced reduction of astrogliosis was a study by Trok et al [31], in which spinal cord explants were allotransplanted into Sprague-Dawley anterior eye chambers
Summary
Spinal cord injury (SCI) is a devastating chronic condition, for which no effective treatments currently exist. The initial SCI mechanical trauma disrupts local vasculature and leads to a breakdown of the blood–spinal cord barrier [2,3,4] This is followed by a secondary wave of injury [5], comprised of hemorrhage, ischemia [6], excitotoxicity, edema, neuronal apoptosis, loss of gray and white matter tissue [6], axonal dieback, chronic inflammation [7], and the formation of a dense astrocytic glial scar surrounding the lesion. Glial cell line-derived neurotrophic factor (GDNF) has been shown to positively modulate astrogliosis [9,10,11], in addition to its known neuroprotective effects, making astrocytes a potential therapeutic target in experimental SCI.
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