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Intravenous human umbilical cord blood transplantation for stroke: Impact on infarct volume and caspase-3-dependent cell death in spontaneously hypertensive rats

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Riegelsberger, Ute-Maria, Deten, Alexander, Pösel, Claudia, Zille, Marietta, Kranz, Alexander, Boltze, Johannes and Wagner, Daniel-Christoph (2011) Intravenous human umbilical cord blood transplantation for stroke: Impact on infarct volume and caspase-3-dependent cell death in spontaneously hypertensive rats. Experimental Neurology, 227 (1). pp. 218-223. doi:10.1016/j.expneurol.2010.11.008 ISSN 00144886.

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Official URL: http://dx.doi.org/10.1016/j.expneurol.2010.11.008

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Abstract

Transplantation of human umbilical cord blood cells (HUCBC) produces reliable behavioral and morphological improvements in animal models of stroke. However, the mechanisms of action still have not been fully elucidated. The aim of the present study is the evaluation of potential neuroprotective effects produced by HUCBC in terms of reduced infarct volume and caspase-3-dependent cell death. Permanent middle cerebral artery occlusion was induced in 90 spontaneously hypertensive rats. The animals were randomly assigned to the control group (n = 49) or the verum group (n = 41). The cell suspension (8 × 106 HUCBC per kilogram bodyweight) or vehicle solution was intravenously administered 24 h after stroke onset. Fifty subjects (n = 25/25) were sacrificed after 25, 48, 72 and 96 h, and brain specimens were removed for immunohistochemistry for MAP2, cleaved caspase-3 (casp3) and GFAP. Another 42 animals (n = 26/16) were sacrificed after 0, 6, 24, 36 and 48 h and their brains processed for quantitative PCR for casp3 and survivin. The infarct volume remained stable over the entire experimental period. However, cleaved casp3 activity increased significantly in the infarct border zone within the same time frame. Numerous cleaved casp3-positive cells were colocalized with the astrocytic marker GFAP, whereas cleavage of neuronal casp3 was observed rarely. Neither the infarct volume nor casp3 activity was significantly affected by cell transplantation. Delayed systemic transplantation of HUCBC failed to produce neuroprotective effects in a permanent stroke model using premorbid subjects.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title: Experimental Neurology
Publisher: Elsevier Inc.
ISSN: 00144886
Official Date: 2011
Dates:
DateEvent
2011Published
Volume: 227
Number: 1
Page Range: pp. 218-223
DOI: 10.1016/j.expneurol.2010.11.008
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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