Delayed 2-h post-stroke administration of R18 and NA-1 (TAT-NR2B9c) peptides after permanent and/or transient middle cerebral artery occlusion in the rat

Following positive results with the poly-arginine peptide R18 when administered intravenously 30 or 60 min after permanent and/or transient middle cerebral artery occlusion (MCAO; 90 min) in the rat, we examined the effectiveness of the peptide when administered 2 h after MCAO. R18 was administered intravenously (1000 nmol/kg via jugular vein) after permanent MCAO or a transient 3-h MCAO or when administered intra-arterially (100 nmol/kg via internal carotid artery) immediately after reperfusion following a transient 2-h MCAO. In the transient MCAO studies, the neuroprotective NA-1 peptide was used as a positive control. Infarct volume, cerebral edema and functional outcomes were measured 24 h after MCAO. Following permanent or transient MCAO, neither R18 nor NA-1 significantly reduced infarct volume. However, following permanent MCAO, R18 appeared to reduce cerebral edema (p = 0.006), whereas following a transient 3-h MCAO, R18 improved the time to remove adhesive tape (p = 0.04) without significantly affecting cerebral edema. There was also a trend (p = 0.07) towards improved rota-rod performance with R18 in both permanent and transient 3-h MCAO. Following a transient 2-h MCAO, R18 had no significant effects on cerebral edema or neurological score but did lessen the extent of weight loss. Overall, while R18 had no effect on infarct volume, the peptide reduced cerebral edema after permanent MCAO, and improved some functional outcomes after transient MCAO.