Neuroprotective effects of insulin like growth factor-1 on engineered metal nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, edema formation, oxidative stress, upregulation of neuronal nitric oxide synthase and brain pathology

Hari Shanker Sharma*, José Vicente Lafuente, Dafin F. Muresanu, Seaab Sahib, Z. Ryan Tian, Preeti K. Menon, Rudy J. Castellani, Ala Nozari, Anca D. Buzoianu, Per Ove Sjöquist, Ranjana Patnaik, Lars Wiklund, Aruna Sharma

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing oxidative stress and/or nitric oxide production. This hypothesis was examined in the rat intoxicated with Ag, Cu or Al (50–60 nm) nanoparticles (50 mg/kg, i.p. once daily) for 7 days. In these NPs treated rats the BBB permeability, brain edema, neuronal nitric oxide synthase (nNOS) immunoreactivity and brain oxidants levels, e.g., myeloperoxidase (MP), malondialdehyde (MD) and glutathione (GT) was examined on the 8th day. Cu and Ag but not Al nanoparticles increased the MP and MD levels by twofold in the brain although, GT showed 50% decline. At this time increase in brain water content and BBB breakdown to protein tracers were seen in areas exhibiting nNOS positive neurons and cell injuries. Pretreatment with insulin like growth factor-1 (IGF-1) in high doses (1 μg/kg, i.v. but not 0.5 μg/kg daily for 7 days) together with NPs significantly reduced the oxidative stress, nNOS upregulation, BBB breakdown, edema formation and cell injuries. These novel observations demonstrate that (i) NPs depending on their metal constituent (Cu, Ag but not Al) induce oxidative stress and nNOS expression leading to BBB disruption, brain edema and cell damage, and (ii) IGF-1 depending on doses exerts powerful neuroprotection against nanoneurotoxicity, not reported earlier.

Original languageEnglish (US)
Title of host publicationProgress in Brain Research
PublisherElsevier B.V.
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Publication series

NameProgress in Brain Research
ISSN (Print)0079-6123
ISSN (Electronic)1875-7855

Keywords

  • Ag
  • Al
  • Brain edema
  • Cell injury
  • Cu
  • Insulin like growth factor-1 (IGF-1)
  • Nanoparticles
  • Nitric oxide
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)

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