Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury

Song, Yu Na; Pimentel, Corrin; Walters, Kate; Boller, Lauren; Ghiasvand, Shabnam; Liu, Jing; Staley, Kevin J.; Berdichevsky, Yevgeny

doi:10.1038/srep32095

Cited by 35 publications

(31 citation statements)

References 67 publications

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“…Insulin-like growth factor 1 (IGF-1) is a polypeptide hormone and functions as primary mediator of growth hormone (GH) dependent growth effects in most peripheral tissues (228). In the brain, IGF-1 regulates the proliferation and differentiation of multiple CNS resident cells and has been implicated in several neurological disorders (229)(230)(231). IGF-1 signals through its cognate receptor IGFR-1R, but can also form functional hybrids with the insulin receptor (229).…”

Section: Igfmentioning

confidence: 99%

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

2020

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Astrocytes play important roles in numerous central nervous system disorders including autoimmune inflammatory, hypoxic, and degenerative diseases such as Multiple Sclerosis, ischemic stroke, and Alzheimer's disease. Depending on the spatial and temporal context, activated astrocytes may contribute to the pathogenesis, progression, and recovery of disease. Recent progress in the dissection of transcriptional responses to varying forms of central nervous system insult has shed light on the mechanisms that govern the complexity of reactive astrocyte functions. While a large body of research focuses on the pathogenic effects of reactive astrocytes, little is known about how they limit inflammation and contribute to tissue regeneration. However, these protective astrocyte pathways might be of relevance for the understanding of the underlying pathology in disease and may lead to novel targeted approaches to treat autoimmune inflammatory and degenerative disorders of the central nervous system. In this review article, we have revisited the emerging concept of protective astrocyte functions and discuss their role in the recovery from inflammatory and ischemic disease as well as their role in degenerative disorders. Focusing on soluble astrocyte derived mediators, we aggregate the existing knowledge on astrocyte functions in the maintenance of homeostasis as well as their reparative and tissue-protective function after acute lesions and in neurodegenerative disorders. Finally, we give an outlook of how these mediators may guide future therapeutic strategies to tackle yet untreatable disorders of the central nervous system.

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Section: Igfmentioning

confidence: 99%

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

2020

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“…The expression of IGF-1 and IGF-1R is significantly changed after cerebral ischemia injury ( 24 ). Also, some researchers have reported that IGF-1 and IGF-1R, which are expressed in the hippocampus, are associated with the loss of neurons ( 25 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

Less hippocampal neuronal death in young gerbils following transient global cerebral ischemia is associated with long‑term maintenance of insulin‑like growth factorï¿½1 and its receptors in the hippocampal CA1 region

et al. 2017

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Insulin-like growth factor 1 (IGF-1) is a well-known growth factor with well-defined neuroprotective effects against cerebral ischemia. However, the age-dependent differences in the expression of IGF-1 and its receptor (IGF-1R) in the brain following transient cerebral ischemia (TCI) have not been elucidated. In the present study, the differences in IGF-1 and IGF-1R in the gerbil hippocampal CA1 region of young and adult gerbils 5 min following TCI were determined. Seven days following TCI, the neuronal death in the hippocampal CA1 region of young gerbils was significantly less than that observed in adult gerbils. In addition, the immunoreactivity, and levels of IGF-1 and IGF-1R in the CA1 region of the normal young were higher than those in the normal adult. Four days following TCI, the immunoreactivity, and protein levels of IGF-1 and IGF-1R were markedly decreased in the adult group. By contrast, in the young group, the immunoreactivity and expression levels were much greater than those in the adult group. However, 7 days following TCI, all immunoreactivity and expression levels were markedly decreased when compared with those in the normal adult and young groups. In addition, the immunoreactivity and expression levels in the young groups were significantly higher than those of the adult groups. In conclusion, the present study demonstrated that the higher and sustained expression of IGF-1 and IGF-1R in the young gerbil hippocampal CA1 region following TCI may be associated with the reduced neuronal death compared to that in the adults.

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“…IGF receptor knockout mice demonstrate systemic upregulation of IGF‐1, contributing to the protection of the brain against hypoxic‐ischemic injury . Additionally, a study with posttraumatic epilepsy models showed that IGF‐1 treatment can be beneficial or harmful depending on the stage of the disease . Therefore, it is important to assess serum IGF‐1 levels and their clinical correlations in various neurodegenerative diseases in which IGF signaling and its receptors in the brain are involved .…”

Section: Discussionmentioning

confidence: 99%

Serum insulin‐like growth factor‐1 levels in neurodegenerative diseases

Suzuki

Ishii

et al. 2019

Acta Neurol Scand

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Background:We investigated serum insulin-like growth factor (IGF)-1 levels in patients with neurodegenerative diseases and correlated these levels with clinical parameters. Methods:One hundred and fifty-six patients with neurodegenerative diseases were included in this study, and serum IGF-1 levels were determined.Results: Serum IGF-1 levels (mean ± standard error) were not significantly different among the patients with different neurodegenerative diseases: Parkinson's disease (PD; n = 73), 112.1 ± 5.1 ng/mL; progressive supranuclear palsy (n = 15), 102.9 ± 8.3 ng/mL; multiple system atrophy (n = 22), 103.1 ± 37.6 ng/mL; Alzheimer's disease (AD; n = 18), 102.2 ± 9.4 ng/mL; amyotrophic lateral sclerosis (n = 6), 105.5 ± 27.4 ng/mL; dementia with Lewy bodies (n = 14), 82.4 ± 7.4 ng/mL; frontotemporal dementia (n = 6), 90.0 ± 17.0 ng/mL; and corticobasal syndrome (n = 2), 118.0 ± 14.0 ng/mL. In patients with PD, serum IGF-1 levels were negatively correlated with age and modified Rankin scale (mRS) scores and positively correlated with the striatal dopamine transporter-specific binding ratio and the frontal assessment battery score. In patients with AD, serum IGF-1 levels were negatively correlated with age, disease duration, and mRS scores. Conclusion:We found correlations of serum IGF-1 levels with frontal lobe and striatal dopaminergic function and disability in PD patients and with disability in AD patients. The usefulness of measuring serum IGF-1 levels for monitoring disease progression in neurodegenerative diseases requires further studies. K E Y W O R D Sdementia disorders, insulin-like growth factor-1, Parkinsonism

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Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury

Cited by 35 publications

References 67 publications

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

Less hippocampal neuronal death in young gerbils following transient global cerebral ischemia is associated with long‑term maintenance of insulin‑like growth factorï¿½1 and its receptors in the hippocampal CA1 region

Serum insulin‐like growth factor‐1 levels in neurodegenerative diseases

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