ELIZA

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501283 occurrences (No.27 in the rank) during 5 years in the PubMed. [cache]

351) Numerous reports highlight behavioral and physiological deficits in blood-brain barrier function and neurovascular communication when IGF-1 levels are low.

--- ABSTRACT ---

PMID:34887742 DOI:10.3389/fnagi.2021.751304

2021 Frontiers in aging neuroscience

* Insulin-Like Growth Factor-1 Differentially Modulates Glutamate-Induced Toxicity and Stress in Cells of the Neurogliovascular Unit.

- The age-related reduction in circulating levels of insulin-like growth factor-1 (IGF-1) is associated with increased risk of stroke and neurodegenerative diseases in advanced age. Numerous reports highlight behavioral and physiological deficits in blood-brain barrier function and neurovascular communication when IGF-1 levels are low. Administration of exogenous IGF-1 reduces the extent of tissue damage and sensorimotor deficits in animal models of ischemic stroke, highlighting the critical role of IGF-1 as a regulator of neurovascular health. The beneficial effects of IGF-1 in the nervous system are often attributed to direct actions on neurons; however, glial cells and the cerebrovasculature are also modulated by IGF-1, and systemic reductions in circulating IGF-1 likely influence the viability and function of the entire neuro-glio-vascular unit. We recently observed that reduced IGF-1 led to impaired glutamate handling in astrocytes. Considering glutamate excitotoxicity is one of the main drivers of neurodegeneration following ischemic stroke, the age-related loss of IGF-1 may also compromise neural function indirectly by altering the function of supporting glia and vasculature. In this study, we assess and compare the effects of IGF-1 signaling on glutamate-induced toxicity and reactive oxygen species (ROS)-produced oxidative stress in primary neuron, astrocyte, and brain microvascular endothelial cell cultures. Our findings verify that neurons are highly susceptible to excitotoxicity, in comparison to astrocytes or endothelial cells, and that a prolonged reduction in IGFR activation increases the extent of toxicity. Moreover, prolonged IGFR inhibition increased the susceptibility of astrocytes to glutamate-induced toxicity and lessened their ability to protect neurons from excitotoxicity. Thus, IGF-1 promotes neuronal survival by acting directly on neurons and indirectly on astrocytes. Despite increased resistance to excitotoxic death, both astrocytes and cerebrovascular endothelial cells exhibit acute increases in glutamate-induced ROS production and mitochondrial dysfunction when IGFR is inhibited at the time of glutamate stimulation. Together these data highlight that each cell type within the neuro-glio-vascular unit differentially responds to stress when IGF-1 signaling was impaired. Therefore, the reductions in circulating IGF-1 observed in advanced age are likely detrimental to the health and function of the entire neuro-glio-vascular unit.

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(2)57 null	(9)4 for	(16)2 as	(23)2 that
(3)39 in	(10)4 the	(17)2 can	(24)2 there
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(6)11 are	(13)2 (p	(20)2 however,	(27)2 while
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--- WordNet output for levels --- Overview of noun level The noun level has 8 senses (first 6 from tagged texts) 1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree") 2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of the highest grade") 3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or especially in a process; "a remarkable degree of frankness"; "at what stage are the social sciences?") 4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the same level") 5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered in a tube of liquid) 6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car on the level") 7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions on many strata simultaneously") 8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single position along a vertical scale; "what level is the office on?") Overview of verb level The verb level has 6 senses (first 3 from tagged texts) 1. (4) level -- (aim at; "level criticism or charges at somebody") 2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make flat with the ground; "The building was levelled") 3. (1) flush, level, even out, even -- (make level or straight; "level the ground") 4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at me") 5. level -- (talk frankly with; lay it on the line; "I have to level with you") 6. level, level off -- (become level or even; "The ground levelled off") --- WordNet end ---