Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury

Lauren Fletcher, Elif Isgor, Shane Sprague, Lindsey H. Williams, Betty B. Alajajian, David F. Jimenez, Murat Digicaylioglu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Insulin-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.Results: Using 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.Conclusions: The 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.

Original languageEnglish (US)
Article number158
JournalBMC Neuroscience
Volume14
DOIs
StatePublished - Dec 21 2013

Fingerprint

Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Proteins
Wounds and Injuries
Stroke
Brain
Astrocytes
Neurons
Middle Cerebral Artery Infarction
Normal Distribution
Microglia
Neuroprotective Agents
Nose
Biological Availability
In Situ Hybridization
Proteins
Ischemia
Animal Models
Messenger RNA

Keywords

  • Insulin-like growth factor binding protein-2
  • Insulin-like growth factor-I
  • Intranasal administration
  • Ischemia
  • Neuroprotection
  • Stroke

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)

Cite this

Fletcher, L., Isgor, E., Sprague, S., Williams, L. H., Alajajian, B. B., Jimenez, D. F., & Digicaylioglu, M. (2013). Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury. BMC Neuroscience, 14, [158]. https://doi.org/10.1186/1471-2202-14-158

Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury. / Fletcher, Lauren; Isgor, Elif; Sprague, Shane; Williams, Lindsey H.; Alajajian, Betty B.; Jimenez, David F.; Digicaylioglu, Murat.

In: BMC Neuroscience, Vol. 14, 158, 21.12.2013.

Research output: Contribution to journalArticle

Fletcher, L, Isgor, E, Sprague, S, Williams, LH, Alajajian, BB, Jimenez, DF & Digicaylioglu, M 2013, 'Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury', BMC Neuroscience, vol. 14, 158. https://doi.org/10.1186/1471-2202-14-158
Fletcher, Lauren ; Isgor, Elif ; Sprague, Shane ; Williams, Lindsey H. ; Alajajian, Betty B. ; Jimenez, David F. ; Digicaylioglu, Murat. / Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury. In: BMC Neuroscience. 2013 ; Vol. 14.
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