Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 30, Issue 3, Pages 653-662Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2009.238
Keywords
administration route; lesion volume; MRI; neural progenitor cell; rat; transient ischemia
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Funding
- National Institute of Neurological Diseases and Stroke [P50 NS23393, PO1 NS42345, RO1 NS48349, RO1 NS38292, RO1 NS43324, HL64766]
- Mort and Brigitte Harris Foundation
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We tested the hypotheses that administration routes affect the migration and distribution of grafted neural progenitor cells (NPCs) in the ischemic brain and that the ischemic lesion plays a role in mediating the grafting process. Male Wistar rats (n = 41) were subjected to 2-h middle cerebral artery occlusion (MCAo), followed 1 day later by administration of magnetically labeled NPCs. Rats with MCAo were assigned to one of three treatment groups targeted for cell transplantation intra-arterially (IA), intracisternally (IC), or intravenously (IV). MRI measurements consisting of T2-weighted imaging and three-dimensional (3D) gradient echo imaging were performed 24 h after MCAo, 4 h after cell injection, and once a day for 4 days. Prussian blue staining was used to identify the labeled cells, 3D MRI to detect cell migration and distribution, and T2 map to assess lesion volumes. Intra-arterial (IA) administration showed significantly increased migration, a far more diffuse distribution pattern, and a larger number of transplanted NPCs in the target brain than IC or IV administration. However, high mortality with IA delivery (IA: 41%; IC: 17%; IV: 8%) poses a serious concern for using this route of administration. Animals with smaller lesions at the time of transplantation have fewer grafted cells in the parenchyma. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 653-662; doi: 10.1038/jcbfm.2009.238; published online 4 November 2009
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