Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic–ischemic injury

Beilharz, Erica; Russo, Vincenzo; Butler, Gary; Baker, Naomi L.; Connor, Bronwen; Sirimanne, Ernest; Dragunow, Mike; Werther, George A.; Gluckman, Peter D.; Williams, Chris; Scheepens, Arjan

doi:10.1016/s0169-328x(98)00122-3

Cited by 191 publications

(123 citation statements)

References 63 publications

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“…However, brain IGF-1 levels are low compared with peripheral tissues such as the liver (Daughaday and Rotwein, 1989). 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: 99%

“…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: 99%

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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“…Increased local synthesis and accumulation of IGF-I is a typical response to brain injury (27). The cells surrounding the lesion site, mostly astroglial cells, contain higher IGF-I and IGF-binding protein immunoreactivity after injury (28,29). Fig.…”

Section: Igf-i Promotes Angiogenesis In Thementioning

confidence: 99%

Insulin-like growth factor I is required for vessel remodeling in the adult brain

López-López

LeRoith

Torres‐Alemán

2004

Proc. Natl. Acad. Sci. U.S.A.

351

274

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Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1␣ and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum͞brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction.

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“…Sections were incubated overnight in 0.01% 5-bromo-4-chloro-3-indolyl-b-D-galactopyranoside (X-gal; Calbiochem, San Diego, CA, USA), 5 mM K 3 Fe(CN) 6 -K 4 Fe(CN) 6 , 2 mM MgCl 2 solution, dehydrated and mounted for light microscopy assessment.…”

Section: Enzymohistochemistrymentioning

confidence: 99%

“…5 Neurotrophic factors that prevent the degeneration and enhance the recovery of remaining DA neurons are of clinical interest. Among them, insulin-like growth factor-I (IGF-I) is emerging as a powerful neuroprotective molecule, which is strongly induced in the CNS after different insults such as ischemia, 6 cortical injury 7,8 and injury of the spinal cord. 9 In situations involving cytotoxic damage in the hippocampus, the microglia of this region dramatically increase the production of IGF-Iand IGF-I-binding protein 2, which suggests a neuroprotective role of these molecules in the CNS.…”

Section: Introductionmentioning

confidence: 99%

Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction

et al. 2006

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Insulin-like growth factor-I (IGF-I) is emerging as a powerful neuroprotective molecule that is strongly induced in the central nervous system after different insults. We constructed a recombinant adenoviral vector (RAd-IGFI) harboring the gene for rat IGF-I and used it to implement IGF-I gene therapy in the hypothalamus of senile female rats, which display hypothalamic dopaminergic (DA) neurodegeneration and as a consequence, chronic hyperprolactinemia. Restorative IGF-I gene therapy was implemented in young (5 months) and senile (28 months) female rats, which received a single intrahypothalamic injection of 3 Â 10 9 plaque-forming units of RAd-bgal (a control adenoviral vector expressing b-galactosidase) or RAd-IGFI and were killed 17 days postinjection. In the young animals, neither vector modified serum prolactin levels, but in the RAd-IGFI-injected senile rats a nearly full reversion of their hyperprolactinemic status was recorded. Morphometric analysis revealed a significant increase in the total number of tyrosine hydroxylase-positive cells in the hypothalamus of experimental as compared with control senile animals (58747486 and 33907498, respectively). Our results indicate that IGF-I gene therapy in senile female rats is highly effective for restoring their hypothalamic DA dysfunction and thus reversing their chronic hyperprolactinemia.

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Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic–ischemic injury

Cited by 191 publications

References 63 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

Insulin-like growth factor I is required for vessel remodeling in the adult brain

Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction

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