Journal article
Chronic enhancement of the intrinsic growth capacity of sensory neurons combined with the degradation of inhibitory proteoglycans allows functional regeneration of sensory axons through the dorsal root entry zone in the mammalian spinal cord
The Journal of neuroscience, v 25(35), pp 8066-8076
31 Aug 2005
PMID: 16135764
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Peripherally conditioned sensory neurons have an increased capacity to regenerate their central processes. However, even conditioned axons struggle in the presence of a hostile CNS environment. We hypothesized that combining an aggressive conditioning strategy with modification of inhibitory reactive astroglial-associated extracellular matrix could enhance regeneration. We screened potential treatments using a model of the dorsal root entry zone (DREZ). In this assay, a gradient of inhibitory chondroitin sulfate proteoglycans (CSPGs) stimulates formation of dystrophic end bulbs on adult sensory axons, which mimics regeneration failure in vivo. Combining inflammation-induced preconditioning of dorsal root ganglia in vivo before harvest, with chondroitinase ABC (ChABC) digestion of proteoglycans in vitro allows for significant regeneration across a once potently inhibitory substrate. We then assessed regeneration through the DREZ after root crush in adult rats receiving the combination treatment, ChABC, or zymosan pretreatment alone or no treatment. Regeneration was never observed in untreated animals, and only minimal regeneration occurred in the ChABC- and zymosan-alone groups. However, remarkable regeneration was observed in a majority of animals that received the combination treatment. Regenerated fibers established functional synapses, as demonstrated electrophysiologically by the presence of an H-reflex. Two different postlesion treatment paradigms in which the timing of both zymosan and ChABC administration were varied after injury were ineffective in promoting regeneration. Therefore, zymosan pretreatment, but not posttreatment, of the sensory ganglia, combined with ChABC modification of CSPGs, resulted in robust and functional regeneration of sensory axons through the DREZ after root injury.
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Details
- Title
- Chronic enhancement of the intrinsic growth capacity of sensory neurons combined with the degradation of inhibitory proteoglycans allows functional regeneration of sensory axons through the dorsal root entry zone in the mammalian spinal cord
- Creators
- Michael P Steinmetz - Department of Neurosurgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USAKevin P HornVeronica J TomJared H MillerSarah A BuschDileep NairDaniel J SilverJerry Silver
- Publication Details
- The Journal of neuroscience, v 25(35), pp 8066-8076
- Publisher
- Society for Neuroscience; United States
- Grant note
- T32 AG00271 / NIA NIH HHS NS25713 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000231565100020
- Scopus ID
- 2-s2.0-24344470604
- Other Identifier
- 991014877784604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences