title: Neuroprotective efficacy of poly-arginine R18 and NA-1 (TAT-NR2B9c) peptides following transient middle cerebral artery occlusion in the rat.
abstract: 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, 1000nmol/kg), 60min after the onset of 90min of MCAO. Infarct volume, cerebral swelling and functional outcomes (neurological score, adhesive tape and rota-rod) were measured 24h 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 30nmol/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 300nmol/kg; p=0.009) and 24.4% (100nmol/kg; p=0.066), while NA-1 reduced swelling by 25.7% (1000nmol/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.
authors.affiliation: School of Heath Sciences, The University Notre Dame Australia, Fremantle, Western Australia 6160, Australia; Western Australian Neuroscience Research Institute, Nedlands 6009, Australia; Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia. Electronic address: diemilani@gmail.com.
authors.forename: Diego
authors.initials: D
authors.lastname: Milani
authors.affiliation: Western Australian Neuroscience Research Institute, Nedlands 6009, Australia; Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands 6009, Australia; Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Cross
authors.affiliation: School of Heath Sciences, The University Notre Dame Australia, Fremantle, Western Australia 6160, Australia; Western Australian Neuroscience Research Institute, Nedlands 6009, Australia.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Anderton
authors.affiliation: Western Australian Neuroscience Research Institute, Nedlands 6009, Australia; Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands 6009, Australia; Department of Neurology, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Blacker
authors.affiliation: Western Australian Neuroscience Research Institute, Nedlands 6009, Australia; Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands 6009, Australia; Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia.
authors.forename: Neville W
authors.initials: NW
authors.lastname: Knuckey
authors.affiliation: Western Australian Neuroscience Research Institute, Nedlands 6009, Australia; Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands 6009, Australia; Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands 6009, Western Australia, Australia.
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Meloni
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D009068:Movement / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; C015462:polyarginine; C542597:Tat-NR2B9c
keywords: NA-1 (TAT-NR2B9c); Neuroprotection; Poly-arginine peptides; R18; Stroke; Transient middle cerebral artery occlusion