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Neuroprotection by Insulin-like Growth Factor-1 in Rats with Ischemic Stroke is Associated with Microglial Changes and a Reduction in Neuroinflammation

Serhan, A., Aerts, J. L., Boddeke, E. W. G. M. & Kooijman, R., 1-Feb-2020, In : Neuroscience. 426, p. 101-114 14 p.

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  • Neuroprotection by Insulin-like Growth Factor-1 in Rats with Ischemic Stroke is Associated with Microglial Changes and a Reduction in Neuroinflammation

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DOI

We and others have shown that insulin-like growth factor-1 (IGF-1) is neuroprotective when administered systemically shortly following stroke. In the current study, we addressed the hypothesis that microglia mediate neuroprotection by IGF-1 following ischemic stroke. Furthermore, we investigated whether IGF-1 modulates pro- and anti-inflammatory mediators in ischemic brain with a special reference to microglia. Ischemic stroke was induced in normal conscious Wistar rats by infusing the vasoconstrictor, endothelin-1 (Et-1), next to middle cerebral artery (MCA). IGF-1 (300 mu g) was injected subcutaneously (SC) at 30 and 120 min following stroke. Microglial inhibitor, minocycline, was injected intraperitoneally (IP) at 1 h before stroke (25 mg/kg) and 11 h after stroke (45 mg/kg). Post-stroke IGF-1 treatment reduced the infarct size and increased the sensorimotor function which coincided with an increase in the number of ameboid microglia in the ischemic cortex. Minocycline treatment abrogated the increase in ameboid microglia by IGF-1, while the effect of IGF-1 in the reduction of infarct size was only partially affected. IGF-1 suppressed mRNA expression of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1 beta in the ischemic hemisphere, while in purified microglia, only iNOS expression levels were reduced. Our findings show that microglia are a target for IGF-1 and that neuroprotection by IGF-1 coincides with down-regulation of inflammatory mediators which could be instrumental to the beneficial effects. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)101-114
Number of pages14
JournalNeuroscience
Volume426
Publication statusPublished - 1-Feb-2020

    Keywords

  • inflammation, neuroprotection, microglia, ischemic stroke, IGF-1, FOCAL CEREBRAL-ISCHEMIA, IGF-I, ACTIVATED MICROGLIA, BRAIN-DAMAGE, NEUTROPHILS, RECEPTOR, INFLAMMATION, IMPAIRMENT, ALTEPLASE, INVASION

ID: 116877444