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BMC Neuroscience

, 14:158

Neurobiology of disease

Abstract

BackgroundInsulin-like growth factor binding protein-2 IGFBP-2 regulates the bioavailability, transportation, and localization of insulin-like growth factor-I IGF-I, an effective neuroprotectant in animal stroke models especially when administered intranasally. Therefore, determining IGFBP-2′s endogenous distribution in the normal and ischemic brain is essential in maximizing the neuroprotective potential of the intranasal IGF-I treatment approach. However, current data on IGFBP-2 is limited to mRNA and in situ hybridization studies. The purpose of this study was to determine if there are any changes in IGFBP-2 protein levels and distribution in ischemic brain and also to determine if IGFBPs play a role in the transportation of intranasally administered IGF-I into the brain.

ResultsUsing an in vitro approach, we show that ischemia causes changes in the distribution of IGFBP-2 in primary cortical neurons and astrocytes. In addition, we show using the transient middle cerebral artery occlusion MCAO model in mice that there is a significant increase in IGFBP-2 levels in the stroke penumbra and core after 72 h. This correlated with an overall increase in IGF-I after stroke, with the highest levels of IGF-I in the stroke core after 72 h. Brain sections from stroke mice indicate that neurons and astrocytes located in the penumbra both have increased expression of IGFBP-2, however, IGFBP-2 was not detected in microglia. We used binding competition studies to show that intranasally administered exogenous IGF-I uptake into the brain is not receptor mediated and is likely facilitated by IGFBPs.

ConclusionsThe change in protein levels indicates that IGFBP-2 plays an IGF-I-dependent and -independent role in the brain’s acute neuroprotection and chronic tissue remodeling response to hypoxic-ischemic injury. Competition studies indicate that IGFBPs may have a role in rapid transportation of exogenous IGF-I from the nasal tissue to the site of injury.

KeywordsStroke Ischemia Neuroprotection Insulin-like growth factor binding protein-2 Insulin-like growth factor-I Intranasal administration Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-14-158 contains supplementary material, which is available to authorized users.

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Author: Lauren Fletcher - Elif Isgor - Shane Sprague - Lindsey H Williams - Betty B Alajajian - David F Jimenez - Murat Digicayl

Source: https://link.springer.com/







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