Journal article
Ex Vivo Gene Therapy Using Targeted Engraftment of NGF-Expressing Human NT2N Neurons Attenuates Cognitive Deficits Following Traumatic Brain Injury in Mice
Journal of neurotrauma, v 21(12), pp 1723-1736
01 Dec 2004
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Infusion of nerve growth factor (NGF) has been shown to be neuroprotective following traumatic brain injury (TBI). In this study, we tested the hypothesis that NGF-expressing human NT2N neurons transplanted into the basal forebrain of brain-injured mice can attenuate long-term cognitive dysfunction associated with TBI. Undifferentiated NT2 cells were transduced in vitro with a lentiviral vector to release NGF, differentiated into NT2N neurons by exposure to retinoic acid and transplanted into the medial septum of mice 24 h following controlled cortical impact (CCI) brain injury or sham injury. Adult mice (n = 78) were randomly assigned to one of four groups: (1) sham-injured and vehicle (serum-free medium)-treated, (2) brain-injured and vehicle-treated, (3) brain-injured engrafted with untransduced NT2N neurons, and (4) brain-injured engrafted with transduced NGF-NT2N neurons. All groups were immunosuppressed daily with cyclosporin A (CsA) for 4 weeks. At 1 month post-transplantation, animals engrafted with NGF-expressing NT2N neurons showed significantly improved learning ability (evaluated with the Morris water maze) compared to brain-injured mice receiving either vehicle (p < 0.05) or untransduced NT2N neurons (p < 0.01). No effect of NGF-secreting NT2N cells on motor function deficits at 1-4 weeks post-transplantation was observed. These data suggest that NGF gene therapy using transduced NT2N neurons (as a source of delivery) may selectively improve cognitive function following TBI.
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Details
- Title
- Ex Vivo Gene Therapy Using Targeted Engraftment of NGF-Expressing Human NT2N Neurons Attenuates Cognitive Deficits Following Traumatic Brain Injury in Mice
- Creators
- Luca LonghiDeborah J. WatsonKathryn E. SaatmanHilaire J. ThompsonChen ZhangScott FujimotoNicolas RoyoDeborah CastelbuonoRamesh RaghupathiJohn Q. TrojanowskiVirginia M.-Y. LeeJohn H. WolfeNino Stocchetti
- Publication Details
- Journal of neurotrauma, v 21(12), pp 1723-1736
- Publisher
- Mary Ann Liebert, Inc; New York
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000225554400004
- Scopus ID
- 2-s2.0-9744266783
- Other Identifier
- 991014877685404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences