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Journal of Neuroscience, Vol 11, 2914-2919, Copyright © 1991 by Society for Neuroscience
Amelioration of delayed neuronal death in the hippocampus by nerve growth factor
T Shigeno, T Mima, K Takakura, DI Graham, G Kato, Y Hashimoto and S Furukawa
Department of Neurosurgery, Saitama Medical Center, Saitama Medical School, Japan.
Selective neuronal death in the CA1 sector of the hippocampus [delayed
neuronal death (DND)] develops several days after transient global cerebral
ischemia in rodents. Because NGF plays a potential role in neuronal
survival, it was decided to study its effect in DND. We report here that
intraventricular injection of NGF either before or after 5 min forebrain
ischemia in the Mongolian gerbil significantly reduced the occurrence of
DND. The tissue content of NGF in the hippocampus was decreased 2 d after
ischemia and recovered to the preischemic level by 1 week. By the Golgi
staining technique, changes first began in the dendrites of affected
neurons as early as 3 hr. Such changes could be ameliorated by NGF
treatment. Although previous knowledge of NGF is limited to the survival of
cholinergic neurons in the CNS, it is assumed that other mechanisms must be
operating in the hippocampus, for example, postsynaptic modification at
dendrites or aberrant expression of NGF receptors possibly at the initial
excitation period by glutamate. Furthermore, because previous work has
shown that inhibition of protein synthesis reduces the occurrence of DND, a
program leading to cell death might also be operating via de novo synthesis
of certain protein(s), collectively termed "killer protein," because of a
lack of NGF.
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