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Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury

Philips, Matthew F.; Mattiasson, Gustav LU ; Wieloch, Tadeusz LU ; Björklund, Anders LU ; Johansson, Barbro LU ; Tomasevic, Gregor LU ; Martinez-Serrano, Alberto; Lenzlinger, Philipp M.; Sinson, Grant and Grady, M. Sean, et al. (2001) In Journal of Neurosurgery 94(5). p.765-765
Abstract
OBJECT: Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. METHODS: Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received... (More)
OBJECT: Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. METHODS: Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). CONCLUSIONS: This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period. (Less)
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published
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keywords
stem cell, growth factor, traumatic brain injury, transplantation, neuroprotection, gene therapy, rat
in
Journal of Neurosurgery
volume
94
issue
5
pages
765 - 765
publisher
American Association of Neurosurgeons
external identifiers
  • pmid:11354408
  • scopus:0034873680
ISSN
0022-3085
language
English
LU publication?
yes
id
21923bb0-4f0a-4f2d-befe-a5bc1d4529ce (old id 1120004)
date added to LUP
2008-07-10 09:48:09
date last changed
2018-03-11 04:05:07
@article{21923bb0-4f0a-4f2d-befe-a5bc1d4529ce,
  abstract     = {OBJECT: Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. METHODS: Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p &lt; 0.05) and spatial learning behavior (p &lt; 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p &lt; 0.025). CONCLUSIONS: This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.},
  author       = {Philips, Matthew F. and Mattiasson, Gustav and Wieloch, Tadeusz and Björklund, Anders and Johansson, Barbro and Tomasevic, Gregor and Martinez-Serrano, Alberto and Lenzlinger, Philipp M. and Sinson, Grant and Grady, M. Sean and McIntosh, Tracy K.},
  issn         = {0022-3085},
  keyword      = {stem cell,growth factor,traumatic brain injury,transplantation,neuroprotection,gene therapy,rat},
  language     = {eng},
  number       = {5},
  pages        = {765--765},
  publisher    = {American Association of Neurosurgeons},
  series       = {Journal of Neurosurgery},
  title        = {Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury},
  volume       = {94},
  year         = {2001},
}