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Promoting Directional Axon Growth from Neural Progenitors Grafted into the Injured Spinal Cord
Journal article   Open access   Peer reviewed

Promoting Directional Axon Growth from Neural Progenitors Grafted into the Injured Spinal Cord

Joseph F. Bonner, Armin Blesch, Birgit Neuhuber and Itzhak Fischer
Journal of neuroscience research, v 88(6), pp 1182-1192
01 May 2010
DOI: https://doi.org/10.1002/jnr.22288
PMID: 19908250
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc2844860View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

brain-derived neurotrophic factor cell transplantation dorsal columns neural stem cells neurotrophin gradients
Spinal cord injury (SCI) is a devastating condition characterized by disruption of axonal connections, failure of axonal regeneration, and loss of motor and sensory function. The therapeutic promise of neural stem cells has been focused on cell replacement but many obstacles remain in getting neuronal integration following transplantation into the injured CNS. In this study we investigated the neurotransmitter identity and axonal growth potential of neural progenitors following grafting into adult rats with a dorsal column lesion. We found that using a combination of neuronal and glial restricted progenitors (NRP and GRP) produced graft-derived glutamatergic and GABAergic neurons within the injury site with minimal axonal extension. Administration of brain derived neurotrophic factor (BDNF) with the graft promoted modest axonal growth from grafted cells. In contrast, injecting a lentiviral vector expressing BDNF rostral to the injury generated a neurotrophin gradient and promoted directional growth of axons for up to 9 mm. Analysis of animals injected with BDNF lentivirus (at 2.5 and 5.0 mm) showed significantly more axons and significantly longer axons than in control animals injected with GFP lentivirus. However, only the 5.0 mm BDNF group showed preference for extension in the rostral direction. We concluded that NRP/GRP grafts can be used to produce excitatory and inhibitory neurons while neurotrophin gradients can guide axonal growth from graft-derived neurons toward putative targets. Together, they can serve as a building block for neuronal cell replacement of local circuits and formation of neuronal relays.

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78 citations in Web of Science
90 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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