Genetically modified fibroblasts producing NGF protect hippocampal neurons after ischemia in the rat.
The neuroprotective effect of nerve growth factor (NGF) on the pyramidal cells in the vulnerable CA1-CA2 sectors of the hippocampus was investigated in a rat model of transient forebrain ischemia. A genetically modified fibroblast line that secretes high levels of NGF was implanted 7 days before induction of ischemia between the hippocampal CA1-CA2 subfields in the right hemisphere. Rats were then subjected to 10 min of cerebral ischemia in a four vessel occlusion model. Morphological changes in the CA1 and CA2 subfields were evaluated 7 days after ischemia. Animals in the NGF-protected group had significantly higher numbers of normal appearing neurons in the right CA1 and CA2 regions, compared with their non-implanted left hemispheres, to non-implanted animals or to animals implanted with non-modified cells. The data confirmed that NGF can protect CA1-CA2 hippocampal neurons from ischemic damage by implantation of genetically engineered cells producing NGF.
Pechan
P A
PA
Molecular Neurogenetics Unit, Massachusetts General Hospital East, Harvard Medical School, Charlestown 02129, USA.
Yoshida
T
T
Panahian
N
N
Moskowitz
M A
MA
Breakefield
X O
XO
D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism* / Q000637:transplantation; D015316:Genetic Therapy; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar
D009414:Nerve Growth Factors