Reduction of ischemic brain injury by topical application of insulin-like growth factor-I after transient middle cerebral artery occlusion in rats

Wang, J.M.; Hayashi, Takeshi; Zhang, W.R.; Sakai, Kenichi; Shiro, Yoshihiko; Abe, K.

doi:10.1016/s0006-8993(00)02008-4

Cited by 74 publications

(45 citation statements)

References 19 publications

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“…Previous reports have shown that IGF-1, its receptors, and binding proteins are all upregulated in response to ischemia and other neurodegenerative conditions (Schwab et al, 1997;Beilharz et al, 1998;Fernandez et al, 1998). This upregulation appears to provide neuroprotection, because exogenous IGF-1 both in vivo and in vitro protects neurons from different types of injury (Tagami et al, 1997;Heck et al, 1999;Guan et al, 2000;Wang et al, 2000;Yamaguchi et al, 2000).…”

Section: Discussionmentioning

confidence: 97%

“…The expression of IGF-1 and its binding proteins are altered in response to brain ischemia (Lee et al, 1996;Schwab et al, 1997;Beilharz et al, 1998), and exogenous administration of IGF-1 significantly reduces neuronal loss in different models of cerebral ischemia (Johnston et al, 1996;Tagami et al, 1997;Guan et al, 2000;Wang et al, 2000). Furthermore, it has been shown that IGF-1 protects cultured neurons against diverse forms of injury, including hypoxia and oxidative stress (Heck et al, 1999;Yamaguchi et al, 2001).…”

Section: Abstract: Global Cerebral Ischemia; Hypoxia-inducible Factomentioning

confidence: 99%

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Activation of Hypoxia-Inducible Factor-1 in the Rat Cerebral Cortex after Transient Global Ischemia: Potential Role of Insulin-Like Growth Factor-1

Chávez¹,

2002

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Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1␣, which accumulates under hypoxic conditions, and a constitutively expressed subunit HIF-1␤.In this study we analyzed HIF-1␣ expression in the rat cerebral cortex after transient global ischemia induced by cardiac arrest and resuscitation. Our results showed that HIF-1␣ accumulates as early as 1 hr of recovery and persists for at least 7 d.In addition, the expression of HIF-1 target genes, erythropoietin and Glut-1, were induced at 12 hr to 7d of recovery. A logical explanation for HIF-1␣ accumulation might be that the brain remained hypoxic for prolonged periods after resuscitation. By using the hypoxic marker 2-(2-nitroimidazole-1[H]-y1)-N- (2,2,3,3,3-pentafluoropropyl)-acetamide (EF5), we showed that the brain is hypoxic during the first hours of recovery from cardiac arrest, but the tissue is no longer hypoxic at 2 d. Thus, the initial ischemic episode must have activated other nonhypoxic mechanisms that maintain prolonged HIF-1␣ accumulation. One such mechanism might be initiated by insulin-like growth factor-1 (IGF-1). Our results showed that IGF-1 expression was upregulated after cardiac arrest and resuscitation. In addition, we showed that IGF-1 was able to induce HIF-1␣ in pheochromocytoma cells and cultured neurons as well as in the brain of rats that received intracerebroventricular and systemic IGF-1 infusion. Moreover, infusion of a selective IGF-1 receptor antagonist abrogates HIF-1␣ accumulation after cardiac arrest and resuscitation. Our study suggest that activation of HIF-1 might be part of the mechanism by which IGF-1 promotes cell survival after cerebral ischemia.

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Section: Discussionmentioning

confidence: 97%

Section: Abstract: Global Cerebral Ischemia; Hypoxia-inducible Factomentioning

confidence: 99%

Activation of Hypoxia-Inducible Factor-1 in the Rat Cerebral Cortex after Transient Global Ischemia: Potential Role of Insulin-Like Growth Factor-1

Chávez¹,

2002

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“…Changes in GSK3b expression were reported after cerebral ischemia. Strong immunoreactivity for GSK3b was observed in the cerebral cortex and dorsal caudate after tFCI, though the authors of these reports did not mention the phosphorylation of GSK3b (Wang et al, 2000;Sasaki et al, 2001). Phosphorylation regulates GSK3b activity in apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Activation of the Akt/GSK3β Signaling Pathway Mediates Survival of Vulnerable Hippocampal Neurons after Transient Global Cerebral Ischemia in Rats

Endo

Nito

Kamada

et al. 2006

J Cereb Blood Flow Metab

173

113

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Recent studies have revealed that the phosphatidylinositol 3-kinase (PI3-K) pathway is involved in apoptotic cell death after experimental cerebral ischemia. The serine-threonine kinase, Akt, functions in the PI3-K pathway and prevents apoptosis by phosphorylation at Ser473 after a variety of cell death stimuli. After phosphorylation, activated Akt inactivates other apoptogenic factors, including glycogen synthase kinase-3b (GSK3b), thereby inhibiting cell death. However, the role of Akt/GSK3b signaling in the delayed death of hippocampal neurons in the CA1 subregion after transient global cerebral ischemia (tGCI) has not been clarified. Transient global cerebral ischemia for 5 mins was induced by bilateral common carotid artery occlusion combined with hypotension. Western blot analysis showed a significant increase in phospho-Akt (Ser473) and phospho-GSK3b (Ser9) in the hippocampal CA1 subregion after tGCI. Immunohistochemistry showed that expression of phospho-Akt (Ser473) and phospho-GSK3b (Ser9) was markedly increased in the vulnerable CA1 subregion, but not in the ischemic-tolerant CA3 subregion. Double staining with phospho-GSK3b (Ser9) and terminal deoxynucleotidyl transferase-mediated uridine 5 0 -triphosphate-biotin nick end labeling showed different cellular distributions in the CA1 subregion 3 days after tGCI. Phosphorylation of Akt and GSK3b was prevented by LY294002, a PI3-K inhibitor, which facilitated subsequent DNA fragmentation 3 days after tGCI. Moreover, transgenic rats that overexpress copper/zinc-superoxide dismutase, which is known to be neuroprotective against delayed hippocampal CA1 injury after tGCI, had enhanced and persistent phosphorylation of both Akt and GSK3b after tGCI. These findings suggest that activation of the Akt/GSK3b signaling pathway may mediate survival of vulnerable hippocampal CA1 neurons after tGCI.

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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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Reduction of ischemic brain injury by topical application of insulin-like growth factor-I after transient middle cerebral artery occlusion in rats

Cited by 74 publications

References 19 publications

Activation of Hypoxia-Inducible Factor-1 in the Rat Cerebral Cortex after Transient Global Ischemia: Potential Role of Insulin-Like Growth Factor-1

Activation of Hypoxia-Inducible Factor-1 in the Rat Cerebral Cortex after Transient Global Ischemia: Potential Role of Insulin-Like Growth Factor-1

Activation of the Akt/GSK3β Signaling Pathway Mediates Survival of Vulnerable Hippocampal Neurons after Transient Global Cerebral Ischemia in Rats

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

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