Basic FGF, NGF, and IGFs Protect Hippocampal and Cortical Neurons against Iron-Induced Degeneration

Abstract

Iron is believed to contribute to the process of cell damage and death resulting from ischemic and traumatic insults by catalyzing the oxidation of protein and lipids. Exposure of cultured rat hippocampal neurons to iron (FeSO4) caused a dose-dependent reduction in neuronal survival, which was potentiated by ascorbate. Damage to neurons was associated with a significant level of oxygen radical in the culture medium. The iron chelator desferal prevented both the neuronal degeneration caused by FeSO4 and the production of oxygen radical, demonstrating that ionic iron was responsible for the cell damage. Iron neurotoxicity was associated with an elevation of [Ca2+]i and was attenuated by NMDA receptor antagonists. Since recent findings demonstrated neuroprotective effects of growth factors in cell culture and in vivo models of ischemia, we examined the effects of growth factors on iron-induced damage. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each protected neurons against iron-induced damage. Both rat hippocampal and human cortical neurons were protected by these growth factors. Taken together, the data suggest that the neuroprotective effects of growth factors against excitotoxic/ischemic insults may result, in part, from a prevention or attenuation of oxidative damage.

Nerve growth factor potentiates the oxidative necrosis of striatal cholinergic neurons

“…Glutamate antagonists did not attenuate Fe 2+ -or BSO-neurotoxicity, excluding the possibility of excitotoxic necrosis secondary to the oxidative stress. 25 Consistent with the observation that BDNF potentiates oxidative neuronal injury, 16 neurons, the small population of striatal neurons responded to NGF. Specifically, pretreatment with NGF as well as BDNF increased the oxidative degeneration of striatal cholinergic neurons known to express TrkA, 9 suggesting that, like other neurotrophins, NGF acts as a pro-necrosis factor via activation of the tyrosine kinase receptor TrkA while it can be a pro-apoptosis factor via activation of the non-tyrosine kinase receptor p75NGFR.…”

Evidence that 4-Hydroxynonenal Mediates Oxidative Stress-Induced Neuronal Apoptosis

“…FeSO 4 and A␤ are known to induce lipid peroxidation and to kill cultured neurons (Poli et al, 1985;Zhang et al, 1993;Behl et al, 1994;Goodman and Mattson, 1994;Muller and Krieglstein, 1995;Goodman et al, 1996). Exposure of PC12-V or PC12-Bcl2 cells to high concentrations of FeSO 4 , A␤, and HNE resulted in rapid decreases in levels of MTT reduction to Ͻ20% of basal levels within 6 hr of exposure ( Fig.…”

Neurovascular Protection by Targeting Early Blood–Brain Barrier Disruption with Neurotrophic Factors after Ischemia–Reperfusion in Rats

“…22 The neuroprotective properties of EGF successfully prevent ferrous sulfate-induced lipid peroxidation and ensuing cell death in neuron cultures. 23 Receptors for EGF, basic fibroblast growth factor (bFGF), BDNF, and NGF use similar downstream transduction pathways, and therefore it may be that EGF rescues ischemic neurons by enhancing activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase. 24 Effect of Epidermal Growth Factor and Pigment EpitheliumDerived Factor on Edema Consistent with earlier findings, 10 in this study tMCAO resulted in significant increases in T 2 values indicative of vasogenic edema formation.…”