Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats

Tien, Lu-Tai; Lee, Yih-Jing; Pang, Yi; Lu, Silu; Lee, Jonathan W.; Tseng, Chih-Hsueh; Bhatt, Abhay; Savich, Renate; Fan, Lir‐Wan

doi:10.1159/000477898

Cited by 27 publications

(21 citation statements)

References 56 publications

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“…In the Central Nervous System the IGF-I is produced by neurons and glial cells[ 18 ] and plays an extensive role in the development, plasticity and survival of neurons. IGF-I involves in the production of neurotransmitters, blocks apoptosis in damaged neurons, and thus has effects on cognition and cognitive decline during ageing or in other neurocognitive disorders like dementia and delirium[ 16 , 19 - 21 ].…”

Section: Introductionmentioning

confidence: 99%

Delirium, insulin-like growth factor I, growth hormone in older inpatients

Adamis¹,

Coada²,

Eikelenboom³

et al. 2020

WJP

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BACKGROUND Delirium is a common disorder in elderly medical inpatients with serious adverse outcomes and is characterized by sudden onset, disturbance in attention, awareness, consciousness and cognition, and often with behavioural disturbances. Central to understanding delirium, is understanding mechanisms by which body and brain wellbeing are linked and in particular how brain responses to bodily homeostatic stress is mediated. A number of studies have investigated the relationship between insulin-like growth factor I (IGF-I) and delirium in medically ill hospitalised patients with conflicting results. However, none have investigated growth hormone (GH) which is related to IGF-I via negative feedback. AIM To investigate the relationship between serum levels of IGF-I and GH, and the occurrence of delirium. METHODS Prospective, longitudinal, observational study. Consecutive elderly inpatients (aged 70+), were assessed twice weekly with Montreal cognitive assessment (MoCA), Confusion assessment method (CAM), Acute Physiology and Chronic Health Evaluation II. Delirium was defined using CAM. Previous history of dementia was evaluated with the Informant Questionnaire on Cognitive Decline in the Elderly. IGF-I and GH levels were estimated with the ELISA method. Generalized estimating equations (GEE) model was applied for the first five assessments to analyze those longitudinal data. RESULTS The sample consisted of 198 participants (mean age 80.63 ± 6.81; range 70-97). Of these 92 (46.5%) were females. Eighty six (43.4%) were identified with a history of dementia. Incident or prevalent delirium during hospitalisation was identified with CAM in 40 participants (20.2%). Evaluation of missing values with Little's MCAR test indicated that they were missing completely at random (MCAR χ 2 = 12.24, u : 9, P = 0.20). Using GEE for the analysis we found that low MoCA scores, low levels of IGF-I and high levels of GH were significantly associated with any delirium (prevalence, incident, or fluctuating , during the study period (Wald χ 2 = 12.231; u : 1, P < 0.001, Wald χ 2 = 7.196, u : 1, P = 0.007, Wald χ 2 = 6.210; : u: 1, P = 0.013 respectively). CONCLUSION The results show that low levels of IGF-I, high levels of GH and low scores in cognition are independently associated with the occurrence of any delirium during the hospitalisation of medically ill older people. The results of the study supports the hypothesis that deficits in the immunoreactivity of the brain (low cerebral reserve) may be...

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Section: Introductionmentioning

confidence: 99%

Delirium, insulin-like growth factor I, growth hormone in older inpatients

Adamis¹,

Coada²,

Eikelenboom³

et al. 2020

WJP

View full text Add to dashboard Cite

show abstract

“…IGF-1 has multiple effects in the CNS, regulating early brain development, myelination, synapse formation, adult neurogenesis, production of neurotransmitters and cognition (Nieto-Estévez et al, 2016 ; Wrigley et al, 2017 ). Furthermore, it is usually considered that IGF-1 is a potent neuroprotective compound (Carro et al, 2003 ; Tien et al, 2017 ), and that this is, at least partially, due to inhibition of neuroinflammation (Sukhanov et al, 2007 ; Park et al, 2011 ). Consistent with this, a decrease in IGF-1 signaling has been related with neurodegeneration, depressive disorders and other brain diseases, in which IGF-1 has been suggested as a possible therapy (Torres Aleman, 2012 ; Guan et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor-1 and Neuroinflammation

Labandeira‐Garcia¹,

Costa-Besada²,

Labandeira³

et al. 2017

Front. Aging Neurosci.

166

130

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Insulin-like growth factor-1 (IGF-1) effects on aging and neurodegeneration is still controversial. However, it is widely admitted that IGF-1 is involved in the neuroinflammatory response. In peripheral tissues, several studies showed that IGF-1 inhibited the expression of inflammatory markers, although other studies concluded that IGF-1 has proinflammatory functions. Furthermore, proinflammatory cytokines such as TNF-α impaired IGF-1 signaling. In the brain, there are controversial results on effects of IGF-1 in neuroinflammation. In addition to direct protective effects on neurons, several studies revealed anti-inflammatory effects of IGF-1 acting on astrocytes and microglia, and that IGF-1 may also inhibit blood brain barrier permeability. Altogether suggests that the aging-related decrease in IGF-1 levels may contribute to the aging-related pro-inflammatory state. IGF-1 inhibits the astrocytic response to inflammatory stimuli, and modulates microglial phenotype (IGF-1 promotes the microglial M2 and inhibits of M1 phenotype). Furthermore, IGF-1 is mitogenic for microglia. IGF-1 and estrogen interact to modulate the neuroinflammatory response and microglial and astrocytic phenotypes. Brain renin-angiotensin and IGF-1 systems also interact to modulate neuroinflammation. Induction of microglial IGF-1 by angiotensin, and possibly by other pro-inflammatory inducers, plays a major role in the repression of the M1 microglial neurotoxic phenotype and the enhancement of the transition to an M2 microglial repair/regenerative phenotype. This mechanism is impaired in aged brains. Aging-related decrease in IGF-1 may contribute to the loss of capacity of microglia to undergo M2 activation. Fine tuning of IGF-1 levels may be critical for regulating the neuroinflammatory response, and IGF-1 may be involved in inflammation in a context-dependent mode.

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“…Two other approaches for MK delivery are of more obvious value for newborn infants. First, the intranasal route, which has been used to deliver diverse proteins to the brains of neonatal and adult experimental animals (e.g., insulin, IGF1, Fgf2, C3a, EGF, anti-tPA, osteopontin) for protection and repair (104,(227)(228)(229)(230). What is lacking here is the experimental data on the distribution of MK after nasal delivery.…”

Section: Challenges and Potential Of Mk Treatment In The Perinatal Pementioning

confidence: 99%

Midkine: The Who, What, Where, and When of a Promising Neurotrophic Therapy for Perinatal Brain Injury

Ross-Munro¹,

Kwa

Kreiner³

et al. 2020

Front. Neurol.

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Midkine (MK) is a small secreted heparin-binding protein highly expressed during embryonic/fetal development which, through interactions with multiple cell surface receptors promotes growth through effects on cell proliferation, migration, and differentiation. MK is upregulated in the adult central nervous system (CNS) after multiple types of experimental injury and has neuroprotective and neuroregenerative properties. The potential for MK as a therapy for developmental brain injury is largely unknown. This review discusses what is known of MK's expression and actions in the developing brain, areas for future research, and the potential for using MK as a therapeutic agent to ameliorate the effects of brain damage caused by insults such as birth-related hypoxia and inflammation.

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Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats

Cited by 27 publications

References 56 publications

Delirium, insulin-like growth factor I, growth hormone in older inpatients

Delirium, insulin-like growth factor I, growth hormone in older inpatients

Insulin-Like Growth Factor-1 and Neuroinflammation

Midkine: The Who, What, Where, and When of a Promising Neurotrophic Therapy for Perinatal Brain Injury

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