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The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor.
Open accessAbstract
Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricular transplants of polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reductions in the number of choline acetyltransferase- (57-75%) and p75 NGF receptor- (53%) immunoreactive medial septal neurons ipsilateral to the lesion/implant. In contrast, monkeys receiving transplants of encapsulated hNGF-secreting cells display only a modest loss of choline acetyltransferase- (0-36%) and p75 NGF receptor-(7-22.4%) immunoreactive septal neurons. Additionally, all monkeys receiving the hNGF-secreting implants, but none receiving control implants, displayed robust sprouting of cholinergic fibers within the septum ipsilateral to the transplant. Just prior to sacrifice, the capsules were retrieved and found to contain viable BHK cells releasing biologically relevant levels of hNGF. These data demonstrate that hNGF can provide trophic and tropic influences to aged primate basal forebrain neurons undergoing lesion-induced degeneration, supporting the contention that hNGF may prevent the degeneration of basal forebrain neurons in Alzheimer disease.
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Cites
Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & DeLong, M. R. (1982) · Science · doi:10.1126/science.7058341 · Cited by 3,627
Nerve Growth Factor Treatment After Brain Injury Prevents Neuronal Death
Kromer, L. F. (1987) · Science · doi:10.1126/science.3798108 · Cited by 932
Benzing, W. C., Ikonomovic, M. D., Brady, D. R., Mufson, E. J., & Armstrong, D. M. (1993) · Journal of Comparative Neurology · doi:10.1002/cne.903340203 · Cited by 46
Self-citation
Cited by
Nerve Growth Factor Signaling, Neuroprotection, and Neural Repair
Sofroniew, M. V., Howe, C. L., & Mobley, W. C. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1217 · Cited by 1,284
Plasma phospholipids identify antecedent memory impairment in older adults
Mapstone, M., Cheema, A. K., Fiandaca, M. S., Zhong, X., Mhyre, T. R., MacArthur, L. H., Hall, W. J., Fisher, S. G., Peterson, D. R., Haley, J. M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3466 · Cited by 1,043
Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier
Lockman, P. R., Mumper, R. J., Khan, M. A., & Allen, D. D. (2002) · Drug Development and Industrial Pharmacy · doi:10.1081/ddc-120001481 · Cited by 592
Host response to tissue engineered devices
Babensee, J. E., Anderson, J. M., McIntire, L. V., & Mikos, A. G. (1998) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(98)00023-4 · Cited by 585
Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease
Tuszynski, M. H., Yang, J. H., Barba, D., U, H.-S., Bakay, R. A. E., Pay, M. M., Masliah, E., Conner, J. M., Kobalka, P., Roy, S., et al. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.1807 · Cited by 287
Metadata
- Authors
- Kordower, J. H., Winn, S. R., Liu, Y. T., Mufson, E. J., Sladek, J. R., Hammang, J. P., Baetge, E. E., & Emerich, D. F.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1994-11-08
- Volume
- 91
- Issue
- 23
- Pages
- 10898-10902
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2060646430
- Cited by
- 192
- References
- 3
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor. https://app.cochat.ai/papers/10.1073/pnas.91.23.10898
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- Kordower, J. H., Winn, S. R., Liu, Y. T., Mufson, E. J., Sladek, J. R., Hammang, J. P., Baetge, E. E., & Emerich, D. F. (1994). The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.23.10898
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
