Muons penetrate much further than X-rays, they do essentially zero damage, and they are provided for free by the cosmos.
Image credit: Science Source/Digital Globe.
Edited by Thomas C. Südhof, Stanford University School of Medicine, Stanford, CA, and approved August 26, 2015 (received for review May 24, 2015)
Significance
Spinal cord injury (SCI) is a debilitating medical condition with no cure at present time. In this study we have discovered that a biodegradable material, chitosan, when loaded with, Neurotrophin-3 (NT3), allowed for slow release of this neural trophic factor, providing an optimal microenvironment for regeneration. NT3-chitosan, when inserted into a 5 mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous neural stem cells forming functional neural networks, which interconnected the severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis by NT3-chitosan could be a novel strategy for treatment of SCI.
Abstract
Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.
Footnotes
- ↵1To whom correspondence may be addressed. Email: wack_lily{at}163.com, yi.eve.sun{at}gmail.com, or lxgchina{at}sina.com.
Author contributions: Z.Y. and X.L. designed research; Z.Y., A.Z., H.D., S.Z., P.H., and X.L. performed research; Z.Y., K.Y., and X.L. analyzed data; and Z.Y. and Y.E.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1510194112/-/DCSupplemental.
Endogenous neurogenesis after SCI
Article Classifications
- Biological Sciences
- Neuroscience
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