A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury

Gluckman, Peter D.; Klempt, N.D.; Guan, Jian; Mallard, Carina; Sirimanne, Ernest; Dragunow, Mike; Klempt, Martin; Singh, Kuljeet; Williams, Chris; Nikolics, Károly

doi:10.1016/0006-291x(92)91774-k

Cited by 372 publications

(186 citation statements)

References 18 publications

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“…This is in contrast to a protective effect of IGF-l in vitro (Mattson et al, 1989;Cheng and Mattson, 1992) and following focal ischemia (Gluckman et al, 1992). The discrepancy could be due to a more dense ischemic insult in duced by transient global ischemia.…”

Section: Discussionmentioning

confidence: 72%

Changes in Insulin-like Growth Factor 1 Receptor Density after Transient Cerebral Ischemia in the Rat. Lack of Protection against Ischemic Brain Damage following Injection of Insulin-Like Growth Factor 1

Bergstedt

Wieloch

1993

J Cereb Blood Flow Metab

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Binding of 125I-insulin-like growth factor-1 (125I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA1 and CA3 regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intracerebroventricular injections of IGF-1 (2 μg) prior to and after transient cerebral ischemia did not reduce neuronal damage. The increased up-regulation on IGF-1 receptors and the absence of neuroprotection by IGF-1 suggest that the intracellular signal transduction chain activated by the IGF-1 receptor may be interrupted.

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Section: Discussionmentioning

confidence: 72%

Changes in Insulin-like Growth Factor 1 Receptor Density after Transient Cerebral Ischemia in the Rat. Lack of Protection against Ischemic Brain Damage following Injection of Insulin-Like Growth Factor 1

Bergstedt

Wieloch

1993

J Cereb Blood Flow Metab

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“…Taking into account the previous observation that Bcl-2 acts upstream of caspase-3 (Chinnaiyan et al, 1996) and the present observation that a caspase-3 inhibitor does not inhibit NO-induced changes in Bcl-2 and Bax protein levels, it is likely that the growth factors inhibit changes in Bcl-2 and Bax protein levels and thereby prevent activation of caspase-3-like protease, resulting in prevention of NO-induced neuronal death. During periods of cerebral ischemia, expression of both IGF-1 and bFGF is increased (Gluckman et al, 1992;Finkelstein et al, 1990;Kiyota et al, 1991). Therefore, it may be that the upregulation of the growth factors following hypoxicischemic insult functions in protecting against NO-induced neuronal death by preventing changes in Bcl-2/Bax expression in vivo.…”

Section: Discussionmentioning

confidence: 99%

Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis induced by nitric oxide

et al. 1998

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Recent studies have shown that nitric oxide (NO) donors can trigger apoptosis of neurons, and growth factors such as insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) can protect against NO-induced neuronal cell death. The purpose of this study was to elucidate the possible mechanisms of NO-mediated neuronal apoptosis and the neuroprotective action of these growth factors. Both IGF-1 and bFGF prevented apoptosis induced by NO donors, sodium nitroprusside (SNP) or 3-morpholinosydnonimin (SIN-1) in hippocampal neuronal cultures. Incubation of neurons with SNP induced caspase-3-like activation following downregulation of Bcl-2 and upregulation of Bax protein levels in cultured neurons. Treatment of neurons with a bax antisense oligonucleotide inhibited the caspase-3-like activation and neuronal death induced by SNP. In addition, treatment of neurons with an inhibitor of caspase-3, Ac-DEVD-CHO, together with SNP did not affect the changes in the protein levels, although it inhibited NO-induced cell death. Pretreatment of cultures with either IGF-1 or bFGF prior to NO exposure inhibited caspase-3-like activation together with the changes in Bcl-2 and Bax protein levels. These results suggest that the changes in Bcl-2 and Bax protein levels followed by caspase-3-like activation are a component in the cascade of NOinduced neuronal apoptosis, and that the neuroprotective actions of IGF-1 and bFGF might be due to inhibition of the changes in the protein levels of the Bcl-2 family.

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“…The scrapie-induced up-regulation of IGF-1R mRNA and protein levels in ScN2a may be part of a trophic response to increased oxidative stress, as IGF-1R activation supports neuronal survival and inhibits cell death in various neurodegenerative disorders (9,10,12). Changes in the IGF-1 system has been reported in various brain insults (2) and evidence indicates that IGF-1R mRNA is up-regulated as a function of aging and cognitive deficits (23,55), consistent with a neuroplastic role of the IGF-1R under degenerative conditions.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of Functionally Impaired Insulin-like Growth Factor-1 Receptor in Scrapie-infected Neuroblastoma Cells

Östlund

Lindegren

Pettersson

et al. 2001

Journal of Biological Chemistry

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A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury

Cited by 372 publications

References 18 publications

Changes in Insulin-like Growth Factor 1 Receptor Density after Transient Cerebral Ischemia in the Rat. Lack of Protection against Ischemic Brain Damage following Injection of Insulin-Like Growth Factor 1

Changes in Insulin-like Growth Factor 1 Receptor Density after Transient Cerebral Ischemia in the Rat. Lack of Protection against Ischemic Brain Damage following Injection of Insulin-Like Growth Factor 1

Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis induced by nitric oxide

Up-regulation of Functionally Impaired Insulin-like Growth Factor-1 Receptor in Scrapie-infected Neuroblastoma Cells

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