Journal
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
Volume 23, Issue 8, Pages 2023-2030Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jstrokecerebrovasdis.2014.02.027
Keywords
Protein transduction; poly-arginine; brain; ischemia
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science (JSPS)
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Direct intracellular delivery of intact proteins has been successfully achieved by tagging cell-penetrating peptide (CPP), which consists of short positively charged amino acids, such as 11 poly-arginine (11R); however, in vivo delivery of the proteins to the brain has remained challenging because it is unclear whether CPP would enable proteins to cross the blood-brain barrier (BBB). In this study, we conducted an in vivo kinetic study to investigate the efficiency of 11R-mediated peptide delivery in the normal and ischemic brain. The 11R was observed in the microvessels and neurons surrounding the microvessels throughout the brain 1 hour after systemic administration, but the signal of the peptide was faint after 2 hours. In a transient middle cerebral artery occlusion mouse model, 11R was markedly enhanced and remained detectable in the cells on the ipsilateral side for as long as 8 hours after administration compared with the contralateral side. These results suggest that 11R is capable of in vivo delivery to the brain by passing through the BBB. Furthermore, 11R-mediated protein transduction could be used for the delivery of therapeutic molecules in cerebral ischemia.
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