Amelioration of delayed neuronal death in the hippocampus by nerve growth factor

Abstract

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.

Brain-Derived Neurotrophic Factor Protects against Ischemic Cell Damage in Rat Hippocampus

“…In contrast to this finding, Buchan et aI. (1990), using a fivefold higher dose than ours in the four-vessel occlusion model and chronically pretreating the rats for 11 days before the insult, and Shigeno et al (1991), injecting gerbils with a bolus roughly six times the total dose we used, did see significant improvements in neurolog ical outcome. A recent publication has underscored the importance of using a sufficiently high NGF dosage for a pharmacological effect (Yamamoto et aI., 1992).…”

Calcium Homeostasis and Reactive Oxygen Species Production in Cells Transformed by Mitochondria from Individuals with Sporadic Alzheimer’s Disease

“…NGF protects neurons against hypoxic, hypoglycemic, and excitotoxic damage in vitro and ischemia in vivo (Cheng and Mattson, 1991;Shigeno et al, 1991;Mattson and Cheng, 1993;Mattson et al, 1993a,c). SH-SY5Y cells possess functional trkA receptors; NGF can differentiate SH-SY5Y cells (Baker et al, 1989;Poluha et al, 1995).…”

Transforming Growth Factor-β1Prevents Glutamate Neurotoxicity in Rat Neocortical Cultures and Protects Mouse Neocortex from Ischemic Injury in vivo

“…In cultured injured rat auditory neurons, TGF-�l enhanced the expression of the fibroblast growth factor (FGF) receptor protein (Lefebvre et al, 1991). Both NGF and FGF have been shown to reduce excitotoxic damage in cul tured mammaliaI) cortical and hippocampal neurons (Mattson et al, 1989;Cheng and Mattson, 1992) and to protect CAl neurons from ischemic damage caused by transient forebrain ischemia in the Mon golian gerbil (Berlove et al, 1991;Shigeno et al, 1991). In addition, it has also been demonstrated that TGF-�l enhances its own expression in cul tured rat astrocytes (Lindholm et al, 1990).…”