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Stroke Research and Treatment
Volume 2016, Article ID 2372710, 9 pages
Research Article

The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat

1School of Health Sciences, The University of Notre Dame Australia, Fremantle, WA 6160, Australia
2Western Australian Neuroscience Research Institute, Nedlands, WA 6009, Australia
3Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, WA 6009, Australia
4Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, WA 6009, Australia

Received 24 February 2016; Accepted 11 April 2016

Academic Editor: David S. Liebeskind

Copyright © 2016 D. Milani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO). The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours after MCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective. The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model. The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke.