title: Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury.
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.
authors.forename: Lauren
authors.initials: L
authors.lastname: Fletcher
authors.forename: Elif
authors.initials: E
authors.lastname: Isgor
authors.forename: Shane
authors.initials: S
authors.lastname: Sprague
authors.forename: Lindsey H
authors.initials: LH
authors.lastname: Williams
authors.forename: Betty B
authors.initials: BB
authors.lastname: Alajajian
authors.forename: David F
authors.initials: DF
authors.lastname: Jimenez
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. muratd@uthscsa.edu.
authors.forename: Murat
authors.initials: M
authors.lastname: Digicaylioglu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I