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, Kerstin; Wieloch, Tadeusz

doi:10.1038/jcbfm.1993.112

Cited by 43 publications

(13 citation statements)

References 24 publications

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“…Receptor levels are altered, however, after some forms of brain injury. For example, increased ligand binding to IGF-1R, suggestive of increased numbers of receptors, was observed at 6 h in the rat hippocampus after cerebral ischemia (Bergstedt and Wieloch, 1993). Nevertheless, little is known about IGF-1R expression in response to TBI.…”

Section: Introductionmentioning

confidence: 99%

Temporal and Regional Changes in IGF-1/IGF-1R Signaling in the Mouse Brain after Traumatic Brain Injury

Madathil

Evans

Saatman

2010

Journal of Neurotrauma

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Although neurotrophic factors such as nerve growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor, and neurotrophin 4=5 are elevated after traumatic brain injury (TBI), little is known about the endogenous response of insulin-like growth factor-1 (IGF-1). We evaluated IGF-1, IGF-1 receptor (IGF-1R), and total and phosphorylated Akt (p-Akt), a known downstream mediator of IGF-1 signaling, using ELISA, Western blotting, and immunohistochemistry at 1, 6, 24, 48, and 72 h following 0.5-mm controlled cortical impact brain injury in adult mice. IGF-1 was transiently upregulated in homogenates of injured cortex at 1 h, and cells with increased IGF-1 immunoreactivity were observed in and around the cortical contusion site up to 48 h. IGF-1R and total Akt levels in cortical homogenates were unchanged, although immunohistochemistry revealed regional changes. In contrast, serine p-Akt levels increased significantly in homogenates at 6 h post-injury. Interestingly, delayed increases in vascular IGF-1R, total Akt, and p-Akt immunostaining were observed in and around the cortical contusion. IGF-1 and its downstream mediators were also upregulated in the subcortical white matter. Our findings indicate that moderate TBI results in a brief induction of IGF-1 and its signaling components in the acute post-traumatic period. This may reflect an attempt at endogenous neuroprotection or repair.

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Section: Introductionmentioning

confidence: 99%

Temporal and Regional Changes in IGF-1/IGF-1R Signaling in the Mouse Brain after Traumatic Brain Injury

Madathil

Evans

Saatman

2010

Journal of Neurotrauma

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“…One of them, insulin-like growth factor 1 (IGF-1) has been implicated in the process of neuronal rescue after brain damage [4,5,[7][8][9]. IGF-1 is a peptide growth factor synthesized in most tissues and regulated primarily by growth hormone (GH) and nutritional status [10].…”

Section: Introductionmentioning

confidence: 99%

Serum Insulin-Like Growth Factor 1 and Growth Hormone Levels of Hypoxic-Ischemic Newborns

et al. 2004

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A number of growth factors, their binding proteins, and their receptors have been shown to be induced in the hypoxic-ischemic (HI) brain. In this prospective study, we aimed at determining the levels of insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol in HI babies and at identifying whether they differ from the levels of control infants. The serum IGF-1 levels were measured after the first 12–24 h of life, and the measurements were repeated on the 5th and 10th days of life for babies with HI encephalopathy (n = 18) and on the 10th day of life for controls (n = 19). Blood samples for measurement of cortisol and GH from both HI and control groups were collected after the first 12–24 h of life. There were 11 babies in the mild-to-moderate (stages I and II) group and 7 babies in the severe (stage III) group according to Sarnat and Sarnat. The IGF-1 levels of the HI group measured after 12–24 h [78.5 ± 27.9 (range 9–123.4) ng/ml] and on the 10th day [72.2 ± 36.8 (range 29.7–159.2) ng/ml] of life were statistically significantly lower than the IGF-1 levels of the control group [121.5 ± 50.4 (range 74.4–280.5) ng/ml and 133.1 ± 34.4 (range 65.9–202) ng/ml, respectively] (p = 0.002 and p = 0.001, respectively). But there was no statistically significant difference between mild-to-moderate HI group and severe HI group in terms of IGF-1 levels after 12–24 h and 5 and 10 days of life (p > 0.05). Also there was no statistically significant difference in IGF-1 values after the first 12–24 h and after 10 days of life between HI subjects who died or survived (p > 0.05). The GH levels of the HI group after the first 12–24 h of life [34.6 ± 32.3 (range 0.1–120) mIU/l] were statistically significantly higher than those in the control group [10.4 ± 4.5 (range 3.7–16.9) mIU/l] (p = 0.005). There was no statistically significant difference in the serum cortisol levels between HI and control groups after the first 12–24 h of life [18.7 ± 17.0 (range 1.6–65.1) µg/dl vs. 10.8 ± 5.4 (range 3.0–23.2) µg/dl] (p > 0.05). No statistically significant correlation was found between IGF-1 levels and GH and cortisol levels of the HI encephalopathy group [r = –0.113 (p > 0.05) and r = 0.108 (p > 0.05), respectively]. In conclusion, this study showed decreased levels of serum IGF-1 and increased levels of GH which may be secondary to serum IGF-1 influx from the circulation to the brain as a protective mechanism or may be due to some cytokines which alter the GH/IGF axis, inhibit the action of IGF-1, and stimulate IGF-binding protein 1.

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“…Hypoxia-ischemia in young rats was associated with an induction of IGFbinding proteins 2 and 5, and reductions of IGF-binding protein 4 [78,79]. Ligand binding of IGF-1 increased transiently after global ischemia [80], and application of IGF-1 was reported to protect adult rats against unilateral ischemic-hypoxic injury [81] and dense forebrain isch emia [82], but a negative report has appeared as well [80]. Finally, increased expression of transforming growth factor-pl in glial cells after global ischemia was reported [83] and transforming growth factor-pi may protect against focal ischemia [84].…”

Section: Trophic Factorsmentioning

confidence: 98%

Genes and Cerebral Ischemia Therapeutic Perspectives

Matsushima¹,

Schmidt‐Kastner²,

Hakim³

1996

Cerebrovasc Dis

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Research into the causes of ischemic damage has evolved into an exploration of the brain's molecular responses. In attempting to discover the specific mechanisms by which ischemic cells die, a number of protective responses which are used by the cells to prolong or assure survival have also been understood, and some of these may become useful therapeutic tools. In this limited review, the mechanisms that are most likely to play a role in determining whether an ischemic cell survives or not are identified and examined. Particular emphasis is placed on the role of immediate early genes, heat shock proteins and trophic factors, and the more recent suspicion that cell cycle genes may be involved in the process of death by apoptosis. As well, the possibility that spreading depression may be a tool that may permit a better understanding of some of these mechanisms as well as offer new therapeutic avenues is examined.

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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

Cited by 43 publications

References 24 publications

Temporal and Regional Changes in IGF-1/IGF-1R Signaling in the Mouse Brain after Traumatic Brain Injury

Temporal and Regional Changes in IGF-1/IGF-1R Signaling in the Mouse Brain after Traumatic Brain Injury

Serum Insulin-Like Growth Factor 1 and Growth Hormone Levels of Hypoxic-Ischemic Newborns

Genes and Cerebral Ischemia Therapeutic Perspectives

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