Neuroprotective efficacy of poly-arginine R18 and NA-1 (TAT-NR2B9c) peptides following transient middle cerebral artery occlusion in the rat

•R18 peptide reduces infarct volume following transient MCAO in the rat.•R18 is neuroprotective when administered 60 min after the onset of MCAO.•R18 reduces cerebral edema and improves functional outcomes.•R18 appears more effective than the highly characterized NA-1 peptide.•R18 is a potential neuroprotective treatment for stroke.

We examined the efficacy of R18 in a transient MCAO model and compared its effectiveness to the well-characterized neuroprotective NA-1 peptide. R18 and NA-1 peptides were administered intravenously (30, 100, 300, 1000 nmol/kg), 60 min after the onset of 90 min of MCAO. Infarct volume, cerebral swelling and functional outcomes (neurological score, adhesive tape and rota-rod) were measured 24 h after MCAO. R18 reduced total infarct volume by 35.1% (p = 0.008), 24.8% (p = 0.059), 12.2% and 9.6% for the respective 1000 to 30 nmol/kg doses, while the corresponding doses of NA-1 reduced lesion volume by 26.1% (p = 0.047), 16.6%, 16.5% and 7%, respectively. R18 also reduced hemisphere swelling by between 46.1% (1000 and 300 nmol/kg; p = 0.009) and 24.4% (100 nmol/kg; p = 0.066), while NA-1 reduced swelling by 25.7% (1000 nmol/kg; p = 0.054). In addition, several R18 and NA-1 treatment groups displayed a significant improvement in at least one parameter of the adhesive tape test. These results confirm the neuroprotective properties of R18, and suggest that the peptide is a more effective neuroprotective agent than NA-1. This provides strong justification for the continuing development of R18 as a neuroprotective treatment for stroke.