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Therefore, determining IGFBP-2\u2032s 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Using an <jats:italic>in vitro<\/jats:italic> 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\u00a0h. This correlated with an overall increase in IGF-I after stroke, with the highest levels of IGF-I in the stroke core after 72\u00a0h. 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The change in protein levels indicates that IGFBP-2 plays an IGF-I-dependent and -independent role in the brain\u2019s 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2202-14-158","type":"journal-article","created":{"date-parts":[[2013,12,21]],"date-time":"2013-12-21T06:02:26Z","timestamp":1387605746000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury"],"prefix":"10.1186","volume":"14","author":[{"given":"Lauren","family":"Fletcher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif","family":"Isgor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shane","family":"Sprague","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey H","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betty B","family":"Alajajian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F","family":"Jimenez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murat","family":"Digicaylioglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,12,21]]},"reference":[{"issue":"11","key":"3839_CR1","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1038\/nn.2953","volume":"14","author":"C Iadecola","year":"2011","unstructured":"Iadecola C, Anrather J: Stroke research at a crossroad: asking the brain for directions. 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